Belatacept in Liver Transplant Recipients
Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Terminated
CT.gov ID
NCT00555321
Collaborator
(none)
260
42
5
41
6.2
0.2
Study Details
Study Description
Brief Summary
The purpose of this clinical research study is to evaluate the effects of belatacept, relative to tacrolimus, on the incidence of rejection, graft loss and death in subjects receiving a liver transplant
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
260 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
Evaluation of Belatacept as First Line Immunosuppression in De Novo Liver Transplant Recipients
Study Start Date
:
Jan 1, 2008
Actual Primary Completion Date
:
Mar 1, 2010
Actual Study Completion Date
:
Jun 1, 2011
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Group 1: Basiliximab+Belatacept (MI) + MMF
|
Drug: Basiliximab
Intravenous (IV), 20 mg, Day1 and Day 5
Drug: Belatacept More Intensive (MI)
Intravenous (IV),
10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24.
After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE])
Drug: Mycophenolate Mofetil (MMF)
Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (Short term [ST]), ≤ 1 g/day, 4 years (Long-term extension [LTE])
|
| Experimental: Group 2: Belatacept (MI) + MMF
|
Drug: Belatacept More Intensive (MI)
Intravenous (IV),
10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24.
After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE])
Drug: Mycophenolate Mofetil (MMF)
Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (Short term [ST]), ≤ 1 g/day, 4 years (Long-term extension [LTE])
|
| Experimental: Group 3: Belatacept Less Intensive (LI) + MMF
|
Drug: Belatacept Less Intensive (LI)
Intravenous (IV),
10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12.
After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (Long-Term Extension(LTE)
Drug: Mycophenolate Mofetil (MMF)
Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (Short term [ST]), ≤ 1 g/day, 4 years (Long-term extension [LTE])
|
| Other: Group 4: Tacrolimus + MMF Other |
Drug: Tacrolimus
Capsules, Oral, dosed to achieve 12 hour trough level of 6-12 ng/mL, twice daily, 52 weeks (Short Term [ST]), in accordance with local practice and the package insert, 4 years (Long-Term Extension [LTE])
Drug: Mycophenolate Mofetil (MMF)
Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (Short term [ST]), ≤ 1 g/day, 4 years (Long-term extension [LTE])
|
| Active Comparator: Group 5: Tacrolimus
|
Drug: Tacrolimus
Capsules, Oral, dosed to achieve 12 hour trough level of 6-12 ng/mL, twice daily, 52 weeks (Short Term [ST]), in accordance with local practice and the package insert, 4 years (Long-Term Extension [LTE])
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Who Experienced at Least One Episode of Acute Rejection (AR), Graft Loss, or Death by 6 Months Post-transplant [At 6 months posttransplant]
Any AR that was clinically suspected and biopsy proven (by central pathologist) was included in this triple composite end point. All biopsies for suspected AR were assessed by a blinded central histopathologist using Banff grading schema. Graft loss was defined as impairment of liver function to such a degree that the participant died or underwent re-transplantation. For 95% (confidence interval) CI within each group, normal approximation is used if N>=5, otherwise exact method is used.
- Number of Participants Who Had Adverse Events (AEs), Death, Serious AEs (SAEs) or Were Discontinued Due to AEs (Includes Long Term Extension [LTE] Data) [Day 1 (randomization) to Week 104 + within 56 Days after the last infusion/dose, Deaths were monitored up to database lock (20-June-2011)]
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
- Number of Participants Who Had AEs of Special Interest During the LTE [Day 1 (randomization) through database lock (20-June-2011)]
AE of special interest included malignancies (including skin carcinomas), infections (viral, cytomegalovirus, herpes, fungal, and bacterial).
- Number of Participants With Marked Hematology Abnormalities During the LTE [Every 4 weeks from Week 53 to Week 104.]
Low platelet count: <50*10^9 c/µl; Low leukocytes: <2.0*10^3 c/µl; Low lymphocytes (absolute): <0.5*10^3 c/µl; Low neutrophils (absolute): <1.0*10^3 c/µl.
- Number of Participants With Marked Liver and Kidney Function Abnormalities During the LTE [Every 4 weeks from Week 53 to Week 104.]
ULN= upper limit of normal; Normal ranges are provided by the Central Laboratory and may vary according to sex and age. High alanine aminotransferase (ALT): >5.0*ULN U/L; High aspartate aminotransferase (AST): >5.0*ULN U/L; High direct bilirubin: >3.0*ULN mg/dL; High g-glutamyl transferase (GGT): >5.0*ULN U/L; High total bilirubin: >3.0*ULN mg/dL; High creatinine: > 3.0*ULN mg/dL
- Number of Participants With Marked Electrolytes, Protein and Metabolic Test Abnormalities During the LTE [Every 4 weeks from Week 53 to Week 104.]
Low Serum Potassium: <3.0 meq/L; High serum potassium:>6.0 mEq/L; Low serum magnesium:<0.8 mEq/L; Low serum sodium: <130 mEq/L; High serum sodium: >155 mEq/L; Low inorganic phosphorus: <2.0 mg/dL; High uric acid: >10 mg/dL
Secondary Outcome Measures
- Percentage of Participants Surviving With Functional Graft: 12-month Treatment Phase [At 6 and 12 months]
For 95% CI within each group, normal approximation was used if N>=5. Otherwise exact method was used.
- Percentage of Participants Surviving With Functional Graft by End of Study (Includes LTE Data) [Day 1 (randomization) through database lock (20-June-2011)]
For 95% CI within each group, normal approximation was used if N>=5, otherwise exact method was used.
- Percentage of Participants Who Experienced at Least One Episode of Acute Rejection, Graft Loss, or Death by 12 Months [At 12 months posttransplant]
Any AR that was clinically suspected and biopsy proven (by central pathologist) was included in this triple composite end point. All biopsies for suspected AR were assessed by a blinded central histopathologist using Banff grading. Graft loss was defined as impairment of liver function to such a degree that the participant died or underwent re-transplantation. For 95% CI within each group, normal approximation is used if N>=5. Otherwise exact method is used. For 95% CI of difference, adjustment is made for randomization strata if N >= 5 in each treatment arm.
- Percentage of Participants Who Experienced at Least One Episode of Acute Rejection, Graft Loss, or Death by End of Study (Includes LTE Data) [Day 1 (randomization) through database lock (20-June-2011)]
Any AR that was clinically suspected and biopsy proven (by central pathologist) was included in this triple composite end point. All biopsies for suspected AR were assessed by a central histopathologist using Banff criteria. For 95% CI within each group, normal approximation was used if N>=5, otherwise exact method was used.
- Number of Participants Having Acute Rejections: 12-month Treatment Phase [3 , 6, and 12 months]
Acute rejections were clinically suspected and biopsy proven by central pathologist. The number of episodes of AR was counted.
- Number of Participants Having Acute Rejections During the LTE [Day 1 (randomization) through database lock (20-June-2011)]
Acute rejections were clinically suspected and biopsy proven by central pathologist. The number of episodes of AR was counted.
- Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type by 12 Months [3, 6 and 12 months posttransplant]
Acute rejections were clinically suspected and biopsy proven by central pathologist. Corticosteroid-resistant rejection = Continued rejection, as documented by liver biopsy, after the completion of 2 days of corticosteroids and requiring use of T-cell depleting agent. Refractory rejection=Continued rejection, as documented by liver biopsy, after use of corticosteroids and T cell depletion therapy. Increase in the dose of TAC was monitored in participants who were assigned to one of the TAC-based regimens. TRT= treatment
- Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type During the LTE [Day 1 (randomization) through database lock (20-June-2011)]
Acute rejections were clinically suspected and biopsy proven by central pathologist. Corticosteroid-resistant rejection = Continued rejection, as documented by liver biopsy, after the completion of 2 days of corticosteroids and requiring use of T-cell depleting agent. Refractory rejection=Continued rejection, as documented by liver biopsy, after use of corticosteroids and T cell depletion therapy. Increase in the dose of TAC was monitored in participants who were assigned to one of the TAC-based regimens. DBL=database lock, TRT=treatment
- Number of Participants Who Had Acute Rejection by Banff Grade by 12 Months [3, 6 and 12 months posttransplant]
Acute Rejections (AR) were clinically suspected and biopsy proven by central pathologist. The Banff grading is a classification of renal allograft pathology and AR. Grade I: AR requiring moderate (>25%) to severe mononuclear cell interstitial infiltrate and moderate tubulitis; Grade II: AR requiring severe tubulitis and/or intimal arteritis; Grade III: AR requiring transmural arteritis. Only the episode with highest Banff grade for each participant was counted.
- Number of Participants With Acute Rejections by Rejection Activity Index (RAI) by 12 Months [3, 6 and 12 months posttransplant]
Acute Rejections were clinically suspected and biopsy proven by central pathologist. The Banff Rejection Activity Index (RAI) comprises 3 components scored from 0 to 3: venous endothelial inflammation; bile duct inflammation damage; and portal inflammation; the scores are combined to an overall score (the RAI). An overall score of 0-2 is considered indeterminate, score of 3-4 is mild, score of 5-6 is moderate, and score of 7-9 is severe. Only the episode with the highest total RAI score for each participant was counted.
- Number of Participants Having Acute Rejection by Rejection Activity Index During the LTE [Day 1 (randomization) through End of study (database lock of 20-June-2011)]
Acute Rejections were clinically suspected and biopsy proven by central pathologist. The Banff Rejection Activity Index (RAI) comprises 3 components scored from 0 to 3: venous endothelial inflammation; bile duct inflammation damage; and portal inflammation; the scores are combined to an overall score (the RAI). An overall score of 0-2 is considered indeterminate, score of 3-4 is mild, score of 5-6 is moderate, and score of 7-9 is severe. Only the episode with the highest total RAI score for each participant was counted.
- Number of Participants at Risk of First Acute Rejection as Determined by Kaplan-Meier Method by 12 Months [3, 6, 9 and 12 months posttransplant]
The time from transplantation to the first AR episode in each treatment arm was summarized using Kaplan-Meier curves. Acute Rejections were clinically suspected and biopsy proven by central pathologist.
- Mean Change From Baseline in Measured Glomerular Filtration Rate (GFR): 12-month Treatment Phase [Baseline (2 month), 12 months posttransplant]
GFR was assessed using a true measure of glomerular filtration via iothalamate clearance test. The month 2 time point was selected as the "baseline" time point with respect to measured GFR due to logistical difficulty in obtaining measured GFR at the time of liver transplant and post-transplant renal function largely stabilizing by 2 months. All Measured GFR > 200 were truncated at 200.
- Mean Change From Baseline in Calculated GFR, by Modification of Diet in Renal Disease (MDRD) Equation: 12-month Treatment Phase [Baseline [BL] (pretransplant time point), 1, 2, 3, 6 and 12 months posttransplant]
GFR is a measure of the rate at which blood is filtered by the kidney. MDRD is an equation (calculation) used to estimate GFR in participants with impaired renal function based on serum creatinine (ScR), age, race, gender, blood urea nitrogen (BUN), and albumin (Alb). GFR (mL/min/1.73 m^2) = 170*(Scr)^-0.999*(Age)^-0.176*(0.762 if female)*(1.180 if African American)*(BUN)^-0.170*(Alb)^+0.318. ). BL= baseline, mL= milliliters; min= minute; m^2= meters squared.
- Mean Change From Baseline in Calculated GFR During the LTE [Baseline (pretransplant time point), 1, 2, 3, 6,12, 18, 24, 30, 36 months posttransplant]
GFR is a measure of the rate at which blood is filtered by the kidney. MDRD is an equation (calculation) used to estimate GFR in participants with impaired renal function based on serum creatinine (ScR), age, race, gender, blood urea nitrogen (BUN), and albumin (Alb). GFR (mL/min/1.73 m^2) = 170*(Scr)^-0.999*(Age)^-0.176*(0.762 if female)*(1.180 if African American)*(BUN)^-0.170*(Alb)^+0.318. ). BL= baseline, mL= milliliters; min= minute; m^2= meters squared.
- Mean Change From Baseline Serum Creatinine at Months 1, 2, 3, 6 and 12 [Baseline (pretransplant time point), 1, 2, 3, 6 and 12 months posttransplant]
Measurement of SCr is commonly used as an indicator of renal function. High creatinine blood level is an indicator of deficient filtering by the kidney. SCr was determined at baseline and various post-baseline time points.
- Mean Change in Baseline Values of Cystatin C at 2 and 12 Months [Baseline (pretransplant), 2, and 12 months posttransplant]
Cystatin C is a protein encoded by the CST3 gene, which is mainly used as a biomarker of kidney function. If kidney function and glomerular filtration rate decline, the blood levels of cystatin C rise.
- Belatacept Pharmacokinetic (PK) Parameter: Maximum Serum Concentration [Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105.]
Maximum Plasma Concentration (Cmax) is the maximum observed serum drug concentration.
- Belatacept Pharmacokinetic (PK) Parameter: Time to Achieve the Maximum Plasma Concentration [Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105.]
Maximum Plasma Concentration (Tmax) is the time taken to reach the maximum observed plasma concentration.
- Belatacept PK Parameter: Area Under the Serum Concentration-time Curve to the End of the Dosing Period (AUCtau) [Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105.]
Area under the plasma concentration-time curve for each dosing interval is determined using the linear trapezoidal rule. The AUC(TAU) of belatacept from the MI regimens and LI regimens were calculated over 2 and 4 weeks respectively.
- Belatacept PK Parameter: Minimum Plasma Concentration [Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105.]
Minimum Plasma Concentration (Cmin) is the minimum observed serum drug concentration.
- Belatacept PK Parameter: Terminal Half-life [Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105.]
Terminal Half-life (T 1/2) is the time a drug takes for the concentration levels to fall to 50% of their value.
- Belatacept PK Parameter: Total Body Clearance [Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105.]
Total body clearance is the rate and extent at which the drug is eliminated from the body. The clearance of a drug is used to understand the processes involved in drug elimination, distribution and metabolism. CLT was estimated from AUC (TAU) between Weeks 12 and 16, assuming steady state.
- Belatacept PK Parameter: Volume of Distribution [Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105.]
Volume of distribution (Vss) is the volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration. . Vss was estimated from AUC (TAU) between Weeks 12 and 16, assuming steady state.
- Belatacept PK Parameter: Amount Excreted in Ascites Fluid Over Days 1 to 14 [Days 1 to 14]
Amount Excreted in Ascites (Ae,asc) was estimated from the ascites drug concentrations and volumes within a dosing interval.
- Belatacept PK Parameter: Clearance From Ascites Fluid [Days 1 to 14]
Clearance from ascites fluid was determined by amount excreted in ascites fluid (Ae, asc)[0-T] / AUC[0-T], where 0-T is the same duration relative to a belatacept infusion.
- Belatacept Trough Concentration Before Each Infusion During the LTE [Samples were collected predose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105, 532, 728.]
Minimum Plasma Concentration (Cmin) is the minimum observed serum drug concentration.
- Percentage of Participants (Who Were Hepatitis C Virus [HCV] Positive at Baseline) With HCV Recurrence (Assessed by Central Pathologist) by 12 Months [6 and 12 months posttransplant]
HCV Recurrence is defined as Histological confirmation on liver biopsy by the Ishak (modified Knodell) system and required both a score >= 5 out of 18 on modified Histological Activity Index grading and a fibrosis Score >= 2 out of 6 on modified staging. All biopsies, including Week 52 biopsies, were considered. Only the first HCV recurrence episode for each participant was counted. For 95% CI within each group, normal approximation was used if N>=5, otherwise exact method was used. For 95% CI of difference, normal approximation was used if N>=5 in both arms, otherwise exact method was used.
- Percentage of Participants (Who Were Hepatitis C Virus [HCV] Positive at Baseline) With HCV Recurrence (Assessed by Central Pathologist) During the LTE [12 months posttransplant, end of study (database lock, 20-June-2011)]
HCV Recurrence is defined as Histological confirmation on liver biopsy by the Ishak (modified Knodell) system and required both a score >= 5 out of 18 on modified Histological Activity Index grading and a fibrosis Score >= 2 out of 6 on modified staging. All biopsies, including Week 52 biopsies, were considered. Only the first HCV recurrence episode for each participant was counted. For 95% CI within each group, normal approximation was used if N>=5, otherwise exact method was used. For 95% CI of difference, normal approximation was used if N>=5 in both arms, otherwise exact method was used.
- Number of Participants (Who Were HCV Positive at Baseline) With HCV Ribonucleic Acid (RNA) Levels >2.4*10^6 U/mL and >4.7*10^6 U/mL: 12-month Treatment Phase [Baseline (pretransplant), 6 and 12 months (mo) posttransplant]
Recurrent hepatitis C infection of the allograft following liver transplantation can be detected by monitoring HCV RNA levels. In HCV positive participants, quantitative HCV RNA levels > 2.4 * 10^6 U/mL and > 4.7 * 10^6 U/mL were descriptively summarized by treatment group. BL=baseline
- Number of Participants (Who Were HCV Positive at Baseline) With HCV RNA Levels >2.4 * 10^6 U/mL and >4.7 * 10^6 U/mL During the LTE [BL (pretransplant), 12, 18, 24, 30 months (mo) posttransplant]
Recurrent hepatitis C infection of the allograft following liver transplantation can be detected by monitoring HCV RNA levels. In HCV positive participants, quantitative HCV RNA levels > 2.4 x 10^6 U/mL and > 4.7 x 10^6 U/mL were descriptively summarized by treatment group. BL = baseline
- Percentage of Participants Who Develop Dyslipidemia, Hypertriglyceridemia and Hypercholesterolemia After Randomization and Transplantation: 12-month Treatment Phase [6 and 12 months posttransplant]
Percentage of participants who develop dyslipidemia, defined as hypertriglyceridemia (triglycerides [TGs] ≥ 500 mg/dL [5.65 mmol/L]), hypercholesterolemia (Low density lipoprotein [LDL] ≥ 100 mg/dL [2.59 mmol/L]), or elevated non-high density lipoprotein (non- high density lipoprotein [HDL] ≥ 130 mg/dL [3.36 mmol/L]) in the presence of high TGs (TGs ≥ 200 mg/dL [2.26 mmol/L]).
- Percentage of Participants Meeting the Definition of Dyslipidemia, Hypertriglyceridemia or Hypercholesterolemia at Any Given Time: 12-month Treatment Phase [6 and 12 months posttransplant]
Percentage of participants at any given time (at Month 6 and Month 12) who met the definition of dyslipidemia.Dyslipidemia is defined as hypertriglyceridemia (TGs ≥ 500 mg/dL [5.65 mmol/L]), hypercholesterolemia (LDL ≥ 100 mg/dL [2.59 mmol/L]), or elevated non-HDL (non-HDL ≥ 130 mg/dL [3.36 mmol/L]) in the presence of high TGs (TGs ≥ 200 mg/dL [2.26 mmol/L]).
- Summary Statistics for Lipid Parameters-Serum Total Non-High Density Lipoprotein (Non-HDL) Cholesterol: 12-month Treatment Phase [Baseline (pretransplant), 1, 6, 12 months posttransplant]
- Summary Statistics for Lipid Parameters; Serum HDL Cholesterol: 12-month Treatment Phase [Baseline (pretransplant), 1, 6, 12 months posttransplant]
- Summary Statistics for Lipid Parameters- Serum Low Density Lipoprotein Cholesterol (LDL): 12-month Treatment Phase [Baseline (pretransplant), 1, 6, 12 months posttransplant]
- Summary Statistics for Lipid Parameters- Serum Cholesterol: 12-month Treatment Phase [Baseline (pretransplant), 1, 6, 12 months posttransplant]
- Summary Statistics for Lipid Parameters - Serum Triglyceride: 12-month Treatment Phase [Baseline (pretransplant), 1, 6, 12 months posttransplant]
- Summary Statistics for Systolic Blood Pressure: 12-month Treatment Phase [Baseline (pretransplant), 1, 3, 6, 9, 12 months posttransplant]
- Summary Statistics for Diastolic Blood Pressure: 12-month Treatment Phase [BL (pretransplant), 1, 3, 6, 9, 12 months posttransplant]
Participants were considered to have hypertension if they had Diastolic Blood Pressure (SBP) ≥ 80 mmHg.
- Summary Statistics for Mean Arterial Pressure: 12-month Treatment Phase [BL (pretransplant), 1, 3, 6, 9, 12 months posttransplant]
- Percentage of Participants Who Developed Hypertension in 12-month Treatment Phase [6 and 12 months posttransplant]
Percentage of participants who develop hypertension after randomization and transplantation. Transient post-operative increases in BP were not to be counted as new onset hypertension. Hypertension was to be assessed only at or after the Week 4 visit. Participants were considered to have hypertension when either of the following criteria were met: (1) SBP ≥ 130 mm Hg or DBP ≥ 80 mm Hg or (2) participant received an antihypertensive medication(s) for the indication of hypertension or due to medical history of hypertension.
- Percentage of Participants Who Have Hypertension at Any Given Time During the 12-month Treatment Phase [6 and 12 months posttransplant]
Percentage of participants at any given time who meet the definition of hypertension. Participants were considered to have hypertension when either of the following criteria were met: (1) SBP ≥ 130 mm Hg or DBP ≥ 80 mm Hg or (2) participant received an antihypertensive medication(s) for the indication of hypertension or due to medical history of hypertension.
- Number of Participants Who Received Anti-hypertensive Therapy at Month 12 [12 months posttransplant]
- Percentage of Participants With New Onset Diabetes Mellitus (NODM): 12-month Treatment Phase [6 and 12 months posttransplant]
A participant who did not have diabetes prior to randomization was determined to have NODM if(i) the participant received an antidiabetic medication for a duration of at least 30 days or(ii) at least two fasting plasma glucose (FPG) tests indicate that FPG is>=126 mg/dL (7.0 mmol/L). For 95% CI within each group, normal approximation is used if N>=5. For 95% CI of difference, adjustment is made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm.
- Glycosylated Hemoglobin (HbA1C) Values: 12-month Treatment Phase [6, 12 months (mth) posttransplant]
The HbA1c test is important in diabetes as a long-term measure of control over blood glucose, where the glucose bound to hemoglobin during the past 3-4 months is measured. A baseline diabetes participant was one who had a medical history of diabetes or being under anti-diabetic medication at the time of the transplantation. BL = baseline, DM = Diabetes mellitus.
- Number of Participants Who Had AEs, Death, SAEs or Were Discontinued Due to AEs: 12-month Treatment Phase [Day 1 (randomization) to 12 m + 8 week follow-up or ≤ 56 days after discontinuation of study medication]
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant administered an investigational product and that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event
- Number of Participants Who Had Adverse Events of Special Interest During 12-month Treatment Phase [Day 1 (randomization) to 12 months or ≤ 56 days after discontinuation of study medication]
AE of of special interest included malignancies (including skin carcinomas), infections (viral, cytomegalovirus, herpes, fungal, and bacterial), serious infections
- Number of Participants With Marked Hematology Abnormalities: 12-month Treatment Phase [Baseline (pretransplant), 2, 4, 8, 12 weeks, and every 4 weeks for week 16 to 52]
Low hemoglobin: <8 g/dL; Low platelet count: <50*10^9 C/L; Low leukocytes: <2.0 *10^3 c/µL; Low lymphocytes (absolute): <0.5*10^3 c/µL; Low neutrophils (absolute): <1.0*10^3 Cc/µL.
- Number of Participants With Marked Liver and Kidney Function Abnormalities: 12-month Treatment Phase [Baseline (pretransplant), 4, 12, 24, 52 weeks]
ULN= upper limit of normal; Normal ranges are provided by the central laboratory and may vary according to sex and age. High alkaline phosphatase (ALP): >5.0*ULN U/L; High alanine aminotransferase (ALT): >5.0*ULN U/L; High aspartate aminotransferase (AST): >5.0*ULN U/L; High direct bilirubin: >3.0 * ULN mg/dL; High g-glutamyl transferase (GGT): >5.0*ULN U/L; High total bilirubin: >3.0*ULN mg/dL; High creatinine: > 3.0*ULN mg/dL
- Number of Participants With Marked Electrolytes, Protein and Metabolic Test Abnormalities: 12-month Treatment Phase [Baseline (pretransplant), Weeks 4, 12, 24, and 52]
Low total calcium: <7 mg/dL; High total calcium: >12.5 mg/dL ; Low bicarbonate: <11 mEq/L; Low serum potassium: <3.0 mEq/L; High serum potassium:>6.0 mEq/L; High serum magnesium: >2.46 mEq/L; Low serum magnesium:<0.8 mEq/L; Low serum sodium: <130 mEq/L; High serum sodium: >155 mEq/L; Low inorganic phosphorus: <2.0 mg/dL; Low albumin: <2 g/dL; High uric acid: >10 mg/dL
- Number of Participants Who Had Abnormalities in Electrocardiograms: 12-month Treatment Phase [Baseline (pretransplant), Week 52]
- Change in Protein to Creatinine Ratio From Month 3 to Month 12. [Month 3 and 12]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
First time recipient of deceased donor liver transplant
-
Age 18-70
-
Hepatitis C virus (HCV) positive recipients
-
For Long-term extension study-Subjects who have completed one year of study treatment (through Week 52)
Target Disease Exclusions:
Donor Exclusions a) Living donors b) ABO-incompatible donor recipient pairs c) Donor age < 12 or > 65 years d) Non heart-beating donors e) Anticipated cold ischemia time > 14 hours
- Donor Disease i) Known Human immunodeficiency virus (HIV) infection ii) Hepatitis B virus (HBV) surface antigen-positive or polymerase chain reaction (PCR)-positive donor if HBV negative recipient iii) HCV antibody-positive or PCR positive donor if HCV negative recipient
Recipient Exclusions g) Subjects with a history of hypercoagulable state h) Subjects with fulminant hepatic failure i) Subjects receiving a split or reduced liver j) Subjects who are Epstein-Barr virus (EBV) negative
Medical History and Concurrent Diseases
-
Subjects who have received 2 or more consecutive weeks of dialysis 1 month prior to enrollment OR anticipated to have prolonged dialysis post-transplantation
-
Subjects with known intrinsic renal disease (e.g., a urine protein/ creatinine ratio > 150 mg/g or the presence of an abnormal number of red blood cells (RBCs) or granular casts in the urine) AND calculated GFR < 40 ml/min/1.73 m^2 body surface area (BSA) (abbreviated Modification of Diet in Renal Disease [MDRD]). Subjects must have a calculated GFR assessment within 1 month prior to enrollment.
-
Subjects with known HIV
-
Subjects with any prior or concurrent solid organ (e.g., heart, kidney, pancreas) or cell (e.g., islet, bone marrow) transplant or subjects deemed likely to have a second solid organ or cell transplant (e.g., islet, bone marrow) within the next 3 years.
-
Subjects with a history of cancer within the last 5 years
Allergies and Adverse Drug Reactions
- Hypersensitivity to any medications that will be used in the protocol
Prohibited Treatments and/or Therapies
-
Subjects receiving immunosuppressive agent(s) (e.g., methotrexate, abatacept, infliximab, etanercept, chemotherapy, etc.) within the past 6 months for other indications such as an autoimmune disease
-
Subjects who received maintenance corticosteroids at a dose of > 5 mg/day of prednisone (or equivalent) for at least 7 consecutive days within the prior year for an underlying chronic inflammatory or autoimmune disease
-
Subjects who have used any investigational drug within 30 days prior to the Day 1 visit
-
Subjects previously treated with belatacept
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic Hospital | Phoenix | Arizona | United States | 85054 |
| 2 | Usc University Hospital | Los Angeles | California | United States | 90033 |
| 3 | University Of California San Francisco Medical Center | San Francisco | California | United States | 94143 |
| 4 | Mayo Clinic Transplant Department | Jacksonville | Florida | United States | 32224 |
| 5 | Lifelink Healthcare Institute | Tampa | Florida | United States | 33606 |
| 6 | Emory University Hospital | Atlanta | Georgia | United States | 30322 |
| 7 | Northwestern University Feinberg School Of Medicine | Chicago | Illinois | United States | 60611 |
| 8 | Tulane Center For Abdominal Transplant | New Orleans | Louisiana | United States | 70112 |
| 9 | Henry Ford Hospital | Detriot | Michigan | United States | 48202 |
| 10 | University Of Minnesota | Minneapolis | Minnesota | United States | 55455 |
| 11 | Washington University School Of Medicine | St. Louis | Missouri | United States | 63110 |
| 12 | Nyu School Of Medicine | New York | New York | United States | 10016 |
| 13 | Westchester Medical Center | Valhalla | New York | United States | 10595 |
| 14 | Carolinas Medical Center | Charlotte | North Carolina | United States | 28203 |
| 15 | Univ. Of Cin. Coll. Of Med. | Cincinnati | Ohio | United States | 45267 |
| 16 | Integris-Baptist Medical Ctr. | Oklahoma City | Oklahoma | United States | 73112 |
| 17 | Hospital Of The University Of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
| 18 | Baylor University Medical Center | Dallas | Texas | United States | 75246 |
| 19 | Froedtert Memorial Lutheran Hospital | Milwaukee | Wisconsin | United States | 53226 |
| 20 | Local Institution | Ciudad De Buenos Aires | Buenos Aires | Argentina | C1181ACH |
| 21 | Local Institution | Wien | Austria | 1090 | |
| 22 | Local Institution | Curitiba | Parana | Brazil | 80060 |
| 23 | Local Institution | Centro-Porto Alegre | Rio Grande Do Sul | Brazil | 90020 |
| 24 | Local Institution | Rio De Janeiro | Brazil | 21041 | |
| 25 | Local Institution | Edmonton | Alberta | Canada | T6G 2B7 |
| 26 | Local Institution | Toronto | Ontario | Canada | M5G 2N2 |
| 27 | Local Institution | Clichy Cedex | France | 92118 | |
| 28 | Local Institution | Lyon | France | 69437 | |
| 29 | Local Institution | Montpellier | France | 34295 | |
| 30 | Local Institution | Paris | France | 75014 | |
| 31 | Local Institution | Toulouse Cedex 9 | France | 31059 | |
| 32 | Local Institution | Villejuif | France | 94800 | |
| 33 | Local Institution | Berlin | Germany | 13353 | |
| 34 | Local Institution | Hamburg | Germany | 20246 | |
| 35 | Local Institution | Hannover | Germany | 30625 | |
| 36 | Local Institution | Heidelberg | Germany | 69120 | |
| 37 | Local Institution | Tuebingen | Germany | 72076 | |
| 38 | Local Institution | Bergamo | Italy | 24128 | |
| 39 | Local Institution | Padova | Italy | 35128 | |
| 40 | Local Institution | Pisa | Italy | 56124 | |
| 41 | Local Institution | Roma | Italy | 00168 | |
| 42 | Local Institution | Barcelona | Spain | 08036 |
Sponsors and Collaborators
- Bristol-Myers Squibb
Investigators
- Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00555321
Other Study ID Numbers:
- IM103-045
First Posted:
Nov 8, 2007
Last Update Posted:
Oct 18, 2012
Last Verified:
Sep 1, 2012
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Period Title: Treatment Phase up to 12-months | |||||
| STARTED | 52 | 51 | 50 | 53 | 54 |
| Received Transplant and Treated | 50 | 48 | 49 | 53 | 50 |
| COMPLETED | 31 | 29 | 26 | 46 | 32 |
| NOT COMPLETED | 21 | 22 | 24 | 7 | 22 |
| Period Title: Treatment Phase up to 12-months | |||||
| STARTED | 30 | 27 | 24 | 38 | 26 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 30 | 27 | 24 | 38 | 26 |
Baseline Characteristics
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) | Total of all reporting groups |
| Overall Participants | 50 | 48 | 49 | 53 | 50 | 250 |
| Age, Customized (participants) [Number] | ||||||
| 18 to 45 years |
7
14%
|
7
14.6%
|
4
8.2%
|
11
20.8%
|
4
8%
|
33
13.2%
|
| 46 to 65 years |
41
82%
|
40
83.3%
|
43
87.8%
|
37
69.8%
|
42
84%
|
203
81.2%
|
| Above 65 years |
2
4%
|
1
2.1%
|
2
4.1%
|
5
9.4%
|
4
8%
|
14
5.6%
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
11
22%
|
14
29.2%
|
18
36.7%
|
7
13.2%
|
8
16%
|
58
23.2%
|
| Male |
39
78%
|
34
70.8%
|
31
63.3%
|
46
86.8%
|
42
84%
|
192
76.8%
|
| Race/Ethnicity, Customized (participants) [Number] | ||||||
| White |
44
88%
|
40
83.3%
|
46
93.9%
|
49
92.5%
|
43
86%
|
222
88.8%
|
| Black / African American |
4
8%
|
3
6.3%
|
1
2%
|
3
5.7%
|
2
4%
|
13
5.2%
|
| American Indian / Alaska native |
0
0%
|
1
2.1%
|
0
0%
|
0
0%
|
0
0%
|
1
0.4%
|
| Asian |
1
2%
|
0
0%
|
2
4.1%
|
0
0%
|
0
0%
|
3
1.2%
|
| Other |
1
2%
|
4
8.3%
|
0
0%
|
1
1.9%
|
5
10%
|
11
4.4%
|
| Race/Ethnicity, Customized (participants) [Number] | ||||||
| Hispanic or Latino (US sites) |
5
10%
|
7
14.6%
|
3
6.1%
|
3
5.7%
|
4
8%
|
22
8.8%
|
| Not Hispanic or Latino (US sites) |
28
56%
|
16
33.3%
|
11
22.4%
|
22
41.5%
|
23
46%
|
100
40%
|
| Unknown (Non- US sites) |
17
34%
|
25
52.1%
|
35
71.4%
|
28
52.8%
|
23
46%
|
128
51.2%
|
| Model for End-Stage Liver Disease (MELD) score (units on a scale) [Median (Full Range) ] | ||||||
| Median (Full Range) [units on a scale] |
22.0
(8.19)
|
22.0
(8.29)
|
22.0
(6.05)
|
24.0
(7.48)
|
22.0
(5.48)
|
22.0
|
| Primary cause of End Stage Liver Disease (ESLD) (participants) [Number] | ||||||
| Non-cholestatic cirrhosis |
38
76%
|
33
68.8%
|
33
67.3%
|
39
73.6%
|
41
82%
|
184
73.6%
|
| Cholestatic liver disease cirrhosis |
0
0%
|
3
6.3%
|
3
6.1%
|
1
1.9%
|
2
4%
|
9
3.6%
|
| Biliary atresia |
0
0%
|
0
0%
|
0
0%
|
1
1.9%
|
0
0%
|
1
0.4%
|
| Acute hepatic necrosis |
4
8%
|
0
0%
|
3
6.1%
|
1
1.9%
|
0
0%
|
8
3.2%
|
| Metabolic disease |
0
0%
|
2
4.2%
|
0
0%
|
1
1.9%
|
0
0%
|
3
1.2%
|
| Malignant neoplasms |
4
8%
|
7
14.6%
|
5
10.2%
|
6
11.3%
|
3
6%
|
25
10%
|
| Other |
4
8%
|
3
6.3%
|
5
10.2%
|
4
7.5%
|
4
8%
|
20
8%
|
| United Network for Organ Sharing (UNOS) Status (participants) [Number] | ||||||
| Status 1 |
0
0%
|
1
2.1%
|
0
0%
|
0
0%
|
0
0%
|
1
0.4%
|
| Status 2A |
1
2%
|
1
2.1%
|
2
4.1%
|
3
5.7%
|
0
0%
|
7
2.8%
|
| Status 2B |
3
6%
|
2
4.2%
|
5
10.2%
|
1
1.9%
|
2
4%
|
13
5.2%
|
| Status 3 |
2
4%
|
2
4.2%
|
2
4.1%
|
1
1.9%
|
1
2%
|
8
3.2%
|
| Not available |
44
88%
|
42
87.5%
|
40
81.6%
|
48
90.6%
|
47
94%
|
221
88.4%
|
| Participants on Anti-Hypertensive Medications (participants) [Number] | ||||||
| No |
41
82%
|
39
81.3%
|
41
83.7%
|
42
79.2%
|
40
80%
|
203
81.2%
|
| Yes |
9
18%
|
9
18.8%
|
8
16.3%
|
11
20.8%
|
10
20%
|
47
18.8%
|
| Participants on Lipid Lowering Medications (participants) [Number] | ||||||
| No |
46
92%
|
43
89.6%
|
48
98%
|
51
96.2%
|
44
88%
|
232
92.8%
|
| Yes |
4
8%
|
5
10.4%
|
1
2%
|
2
3.8%
|
6
12%
|
18
7.2%
|
| Participants on Anti-diabetic Medications (participants) [Number] | ||||||
| No |
35
70%
|
35
72.9%
|
40
81.6%
|
41
77.4%
|
38
76%
|
189
75.6%
|
| Yes |
15
30%
|
13
27.1%
|
9
18.4%
|
12
22.6%
|
12
24%
|
61
24.4%
|
Outcome Measures
| Title | Percentage of Participants Who Experienced at Least One Episode of Acute Rejection (AR), Graft Loss, or Death by 6 Months Post-transplant |
|---|---|
| Description | Any AR that was clinically suspected and biopsy proven (by central pathologist) was included in this triple composite end point. All biopsies for suspected AR were assessed by a blinded central histopathologist using Banff grading schema. Graft loss was defined as impairment of liver function to such a degree that the participant died or underwent re-transplantation. For 95% (confidence interval) CI within each group, normal approximation is used if N>=5, otherwise exact method is used. |
| Time Frame | At 6 months posttransplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) population: all randomized and transplanted participants. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 50 | 48 | 49 | 53 | 50 |
| Number (95% Confidence Interval) [percentage of participants] |
48.0
96%
|
41.7
86.9%
|
46.9
95.7%
|
15.1
28.5%
|
38.0
76%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 32.9 | |
| Confidence Interval |
(2-Sided) 95% 16.1 to 49.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 26.6 | |
| Confidence Interval |
(2-Sided) 95% 9.6 to 43.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 31.8 | |
| Confidence Interval |
(2-Sided) 95% 14.8 to 48.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 10.0 | |
| Confidence Interval |
(2-Sided) 95% -8.7 to 29.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 3.7 | |
| Confidence Interval |
(2-Sided) 95% -15.3 to 23.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 8.9 | |
| Confidence Interval |
(2-Sided) 95% -9.8 to 28.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
| Title | Percentage of Participants Surviving With Functional Graft: 12-month Treatment Phase |
|---|---|
| Description | For 95% CI within each group, normal approximation was used if N>=5. Otherwise exact method was used. |
| Time Frame | At 6 and 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population: all randomized and transplanted participants. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 50 | 48 | 49 | 53 | 50 |
| At 6 months |
90.0
180%
|
89.6
186.7%
|
77.6
158.4%
|
92.5
174.5%
|
90.0
180%
|
| At 12 months |
90.0
180%
|
83.3
173.5%
|
67.3
137.3%
|
92.5
174.5%
|
88.0
176%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 6 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -2.5 | |
| Confidence Interval |
(2-Sided) 95% -12.9 to 8.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 6 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -2.9 | |
| Confidence Interval |
(2-Sided) 95% -13.6 to 8.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 6 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -14.9 | |
| Confidence Interval |
(2-Sided) 95% -23.8 to 1.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 6 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 6 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.4 | |
| Confidence Interval |
(2-Sided) 95% -12.1 to 11.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 6 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -12.4 | |
| Confidence Interval |
(2-Sided) 95% -22.9 to 4.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -2.5 | |
| Confidence Interval |
(2-Sided) 95% -12.9 to 8.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -9.1 | |
| Confidence Interval |
(2-Sided) 95% -18.1 to 5.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -25.1 | |
| Confidence Interval |
(2-Sided) 95% -38.9 to -9.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 2.0 | |
| Confidence Interval |
(2-Sided) 95% -9.9 to 14.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -4.7 | |
| Confidence Interval |
(2-Sided) 95% -15.5 to 10.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -20.7 | |
| Confidence Interval |
(2-Sided) 95% -35.5 to -4.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
| Title | Percentage of Participants Surviving With Functional Graft by End of Study (Includes LTE Data) |
|---|---|
| Description | For 95% CI within each group, normal approximation was used if N>=5, otherwise exact method was used. |
| Time Frame | Day 1 (randomization) through database lock (20-June-2011) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT-LTE population, all randomized and transplanted participants who entered long term extension. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 30 | 27 | 24 | 38 | 26 |
| Number (95% Confidence Interval) [percentage of participants] |
93.3
186.6%
|
85.2
177.5%
|
95.8
195.5%
|
92.1
173.8%
|
96.2
192.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 1.2 | |
| Confidence Interval |
(2-Sided) 95% -14.5 to 15.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N>=5 in both arms. Otherwise exact method was used. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -6.9 | |
| Confidence Interval |
(2-Sided) 95% -25.7 to 8.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N>=5 in both arms. Otherwise exact method was used. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 3.7 | |
| Confidence Interval |
(2-Sided) 95% -13.2 to 17.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N>=5 in both arms. Otherwise exact method was used. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -2.8 | |
| Confidence Interval |
(2-Sided) 95% -18.1 to 13.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N>=5 in both arms. Otherwise exact method was used. | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -11.0 | |
| Confidence Interval |
(2-Sided) 95% -29.4 to 6.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N>=5 in both arms. Otherwise exact method was used. | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.3 | |
| Confidence Interval |
(2-Sided) 95% -16.9 to 15.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N>=5 in both arms. Otherwise exact method was used. | |
| Title | Percentage of Participants Who Experienced at Least One Episode of Acute Rejection, Graft Loss, or Death by 12 Months |
|---|---|
| Description | Any AR that was clinically suspected and biopsy proven (by central pathologist) was included in this triple composite end point. All biopsies for suspected AR were assessed by a blinded central histopathologist using Banff grading. Graft loss was defined as impairment of liver function to such a degree that the participant died or underwent re-transplantation. For 95% CI within each group, normal approximation is used if N>=5. Otherwise exact method is used. For 95% CI of difference, adjustment is made for randomization strata if N >= 5 in each treatment arm. |
| Time Frame | At 12 months posttransplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population: all randomized and transplanted participants |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 50 | 48 | 49 | 53 | 50 |
| Number (95% Confidence Interval) [percentage of participants] |
52.0
104%
|
47.9
99.8%
|
53.1
108.4%
|
18.9
35.7%
|
40.0
80%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 33.1 | |
| Confidence Interval |
(2-Sided) 95% 15.8 to 50.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 29.0 | |
| Confidence Interval |
(2-Sided) 95% 11.4 to 46.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 34.2 | |
| Confidence Interval |
(2-Sided) 95% 16.9 to 51.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 12.0 | |
| Confidence Interval |
(2-Sided) 95% -7.1 to 31.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 7.9 | |
| Confidence Interval |
(2-Sided) 95% -11.5 to 27.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 13.1 | |
| Confidence Interval |
(2-Sided) 95% -5.9 to 32.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
| Title | Percentage of Participants Who Experienced at Least One Episode of Acute Rejection, Graft Loss, or Death by End of Study (Includes LTE Data) |
|---|---|
| Description | Any AR that was clinically suspected and biopsy proven (by central pathologist) was included in this triple composite end point. All biopsies for suspected AR were assessed by a central histopathologist using Banff criteria. For 95% CI within each group, normal approximation was used if N>=5, otherwise exact method was used. |
| Time Frame | Day 1 (randomization) through database lock (20-June-2011) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT-LTE population: all randomized and transplanted participants who entered the Long term extension |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 30 | 27 | 24 | 38 | 26 |
| Number (95% Confidence Interval) [percentage of participants] |
36.7
73.4%
|
37.0
77.1%
|
25.0
51%
|
21.1
39.8%
|
23.1
46.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 15.6 | |
| Confidence Interval |
(2-Sided) 95% -5.8 to 36.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N>=5 in both arms. Otherwise exact method was used. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 16.0 | |
| Confidence Interval |
(2-Sided) 95% -6.0 to 38.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N>=5 in both arms. Otherwise exact method was used. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 3.9 | |
| Confidence Interval |
(2-Sided) 95% -16.6 to 26.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N>=5 in both arms. Otherwise exact method was used. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 13.6 | |
| Confidence Interval |
(2-Sided) 95% -10.8 to 36.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N>=5 in both arms. Otherwise exact method was used. | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 14.0 | |
| Confidence Interval |
(2-Sided) 95% -10.9 to 37.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N>=5 in both arms. Otherwise exact method was used. | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 1.9 | |
| Confidence Interval |
(2-Sided) 95% -21.8 to 26.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N>=5 in both arms. Otherwise exact method was used. | |
| Title | Number of Participants Having Acute Rejections: 12-month Treatment Phase |
|---|---|
| Description | Acute rejections were clinically suspected and biopsy proven by central pathologist. The number of episodes of AR was counted. |
| Time Frame | 3 , 6, and 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population: all randomized and transplanted participants |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 50 | 48 | 49 | 53 | 50 |
| By 3 months ; Overall |
17
34%
|
15
31.3%
|
14
28.6%
|
4
7.5%
|
13
26%
|
| By 3 months ; 1 episode |
15
30%
|
14
29.2%
|
14
28.6%
|
4
7.5%
|
12
24%
|
| By 3 months ; 2 episodes |
1
2%
|
1
2.1%
|
0
0%
|
0
0%
|
1
2%
|
| By 3 months ; >2 episodes |
1
2%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| By 6 months ; Overall |
20
40%
|
15
31.3%
|
15
30.6%
|
5
9.4%
|
15
30%
|
| By 6 months ; 1 episode |
18
36%
|
12
25%
|
14
28.6%
|
4
7.5%
|
13
26%
|
| By 6 months ; 2 episodes |
1
2%
|
3
6.3%
|
1
2%
|
1
1.9%
|
2
4%
|
| By 6 months ; >2 episodes |
1
2%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| By 12 months ; Overall |
22
44%
|
16
33.3%
|
16
32.7%
|
7
13.2%
|
15
30%
|
| By 12 months ; 1 episode |
18
36%
|
13
27.1%
|
14
28.6%
|
6
11.3%
|
13
26%
|
| By 12 months ; 2 episodes |
3
6%
|
3
6.3%
|
2
4.1%
|
1
1.9%
|
2
4%
|
| By 12 months ; >2 episodes |
1
2%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants Having Acute Rejections During the LTE |
|---|---|
| Description | Acute rejections were clinically suspected and biopsy proven by central pathologist. The number of episodes of AR was counted. |
| Time Frame | Day 1 (randomization) through database lock (20-June-2011) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT-LTE population, all randomized and transplanted participants who entered long-term extension |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 30 | 27 | 24 | 38 | 26 |
| By 12 months (m); Overall |
9
18%
|
6
12.5%
|
6
12.2%
|
6
11.3%
|
6
12%
|
| By 12 m ; 1 episode |
8
16%
|
6
12.5%
|
5
10.2%
|
5
9.4%
|
5
10%
|
| By 12 m ; 2 episodes |
1
2%
|
0
0%
|
1
2%
|
1
1.9%
|
1
2%
|
| By 12 m; >2 episodes |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| By Database lock; Overall |
9
18%
|
6
12.5%
|
6
12.2%
|
6
11.3%
|
6
12%
|
| By Database lock ; 1 episode |
8
16%
|
6
12.5%
|
5
10.2%
|
5
9.4%
|
5
10%
|
| By Database lock ; 2 episodes |
1
2%
|
0
0%
|
1
2%
|
1
1.9%
|
0
0%
|
| By Database lock ; >2 episodes |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
2%
|
| Title | Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type by 12 Months |
|---|---|
| Description | Acute rejections were clinically suspected and biopsy proven by central pathologist. Corticosteroid-resistant rejection = Continued rejection, as documented by liver biopsy, after the completion of 2 days of corticosteroids and requiring use of T-cell depleting agent. Refractory rejection=Continued rejection, as documented by liver biopsy, after use of corticosteroids and T cell depletion therapy. Increase in the dose of TAC was monitored in participants who were assigned to one of the TAC-based regimens. TRT= treatment |
| Time Frame | 3, 6 and 12 months posttransplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population: all randomized and transplanted participants |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 50 | 48 | 49 | 53 | 50 |
| By 3 months: Acute rejections |
7
14%
|
15
31.3%
|
14
28.6%
|
4
7.5%
|
13
26%
|
| By 3 months: Treated participants |
10
20%
|
11
22.9%
|
7
14.3%
|
3
5.7%
|
10
20%
|
| By 3 months: Corticosteroid treatment Only |
10
20%
|
7
14.6%
|
7
14.3%
|
2
3.8%
|
9
18%
|
| By 3 months: Corticosteroid resistant |
0
0%
|
1
2.1%
|
0
0%
|
0
0%
|
0
0%
|
| By 3 months: Refractory |
0
0%
|
1
2.1%
|
0
0%
|
0
0%
|
0
0%
|
| By3 months: Initial lymphocyte depleting TRT |
0
0%
|
2
4.2%
|
0
0%
|
0
0%
|
0
0%
|
| By 3 months: Increase in dose of Tacrolimus |
0
0%
|
0
0%
|
0
0%
|
1
1.9%
|
1
2%
|
| By 3 months: Other / not available |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| By 6 months: Acute rejections |
20
40%
|
15
31.3%
|
15
30.6%
|
5
9.4%
|
15
30%
|
| By 6 months: Treated participants |
12
24%
|
11
22.9%
|
8
16.3%
|
4
7.5%
|
12
24%
|
| By 6 months: Corticosteroid treatment Only |
12
24%
|
6
12.5%
|
8
16.3%
|
3
5.7%
|
10
20%
|
| By 6 months: Corticosteroid resistant |
0
0%
|
1
2.1%
|
0
0%
|
0
0%
|
0
0%
|
| By 6 months: Refractory |
0
0%
|
1
2.1%
|
0
0%
|
0
0%
|
0
0%
|
| By 6 months: Initial lymphocyte depleting TRT |
0
0%
|
3
6.3%
|
0
0%
|
0
0%
|
0
0%
|
| By 6 months: Increase in dose of Tacrolimus |
0
0%
|
0
0%
|
0
0%
|
1
1.9%
|
1
2%
|
| By 6 months: Other / not available |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
2%
|
| By 12 months: Acute rejections |
22
44%
|
16
33.3%
|
16
32.7%
|
7
13.2%
|
15
30%
|
| By 12 months: Treated participants |
12
24%
|
12
25%
|
8
16.3%
|
5
9.4%
|
2
4%
|
| By 12 months: Corticosteroid treatment Only |
12
24%
|
7
14.6%
|
8
16.3%
|
4
7.5%
|
10
20%
|
| By 12 months: Corticosteroid resistant |
0
0%
|
1
2.1%
|
0
0%
|
0
0%
|
0
0%
|
| By 12 months: Refractory |
0
0%
|
1
2.1%
|
0
0%
|
0
0%
|
0
0%
|
| B12 months: Initial lymphocyte depleting TRT |
0
0%
|
3
6.3%
|
0
0%
|
0
0%
|
0
0%
|
| 12 months: Other / not available |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
2%
|
| Title | Number of Participants With Central Biopsy Proven Acute Rejection by Treatment Type During the LTE |
|---|---|
| Description | Acute rejections were clinically suspected and biopsy proven by central pathologist. Corticosteroid-resistant rejection = Continued rejection, as documented by liver biopsy, after the completion of 2 days of corticosteroids and requiring use of T-cell depleting agent. Refractory rejection=Continued rejection, as documented by liver biopsy, after use of corticosteroids and T cell depletion therapy. Increase in the dose of TAC was monitored in participants who were assigned to one of the TAC-based regimens. DBL=database lock, TRT=treatment |
| Time Frame | Day 1 (randomization) through database lock (20-June-2011) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT-LTE population, all randomized and transplanted participants who entered long term extension. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 30 | 27 | 24 | 38 | 26 |
| By 12 months: Acute rejections |
9
18%
|
6
12.5%
|
6
12.2%
|
6
11.3%
|
6
12%
|
| By 12 months: Treated participants |
4
8%
|
5
10.4%
|
4
8.2%
|
5
9.4%
|
6
12%
|
| By 12 months: Corticosteroid treatment Only |
4
8%
|
4
8.3%
|
4
8.2%
|
4
7.5%
|
5
10%
|
| By 12 months: Corticosteroid resistant |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| By 12 months: Refractory |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| By 12 months: Initial lymphocyte depleting TRT |
0
0%
|
1
2.1%
|
0
0%
|
0
0%
|
0
0%
|
| By 12 months: Other / not available |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| By 12 months: Increase in dose of TAC |
0
0%
|
0
0%
|
0
0%
|
1
1.9%
|
0
0%
|
| By DBL: Acute rejections |
9
18%
|
6
12.5%
|
6
12.2%
|
6
11.3%
|
6
12%
|
| By DBL: Treated participants |
4
8%
|
5
10.4%
|
4
8.2%
|
5
9.4%
|
6
12%
|
| By DBL: Corticosteroid treatment Only |
4
8%
|
4
8.3%
|
4
8.2%
|
4
7.5%
|
5
10%
|
| By DBL: Corticosteroid resistant |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| By DBL: Refractory |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| By DBL: Initial lymphocyte depleting treatment |
0
0%
|
1
2.1%
|
0
0%
|
0
0%
|
0
0%
|
| By DBL: Other/ Not available |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| By DBL: Increase in dose of TAC |
0
0%
|
0
0%
|
0
0%
|
1
1.9%
|
1
2%
|
| Title | Number of Participants Who Had Acute Rejection by Banff Grade by 12 Months |
|---|---|
| Description | Acute Rejections (AR) were clinically suspected and biopsy proven by central pathologist. The Banff grading is a classification of renal allograft pathology and AR. Grade I: AR requiring moderate (>25%) to severe mononuclear cell interstitial infiltrate and moderate tubulitis; Grade II: AR requiring severe tubulitis and/or intimal arteritis; Grade III: AR requiring transmural arteritis. Only the episode with highest Banff grade for each participant was counted. |
| Time Frame | 3, 6 and 12 months posttransplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population: all randomized and transplanted participants |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 50 | 48 | 49 | 53 | 50 |
| By 3 months: Grade 1 |
14
28%
|
8
16.7%
|
7
14.3%
|
3
5.7%
|
6
12%
|
| By 3 months: Grade 2 |
3
6%
|
6
12.5%
|
6
12.2%
|
1
1.9%
|
5
10%
|
| By 3 months: Grade 3 |
0
0%
|
1
2.1%
|
1
2%
|
0
0%
|
2
4%
|
| By 6 months: Grade 1 |
16
32%
|
6
12.5%
|
7
14.3%
|
4
7.5%
|
7
14%
|
| By 6 months: Grade 2 |
4
8%
|
8
16.7%
|
7
14.3%
|
1
1.9%
|
6
12%
|
| By 6 months: Grade 3 |
0
0%
|
1
2.1%
|
1
2%
|
0
0%
|
2
4%
|
| By 12 months: Grade 1 |
15
30%
|
7
14.6%
|
7
14.3%
|
6
11.3%
|
7
14%
|
| By 12 months: Grade 2 |
7
14%
|
8
16.7%
|
8
16.3%
|
1
1.9%
|
6
12%
|
| By 12 months: Grade 3 |
0
0%
|
1
2.1%
|
1
2%
|
0
0%
|
2
4%
|
| Title | Number of Participants With Acute Rejections by Rejection Activity Index (RAI) by 12 Months |
|---|---|
| Description | Acute Rejections were clinically suspected and biopsy proven by central pathologist. The Banff Rejection Activity Index (RAI) comprises 3 components scored from 0 to 3: venous endothelial inflammation; bile duct inflammation damage; and portal inflammation; the scores are combined to an overall score (the RAI). An overall score of 0-2 is considered indeterminate, score of 3-4 is mild, score of 5-6 is moderate, and score of 7-9 is severe. Only the episode with the highest total RAI score for each participant was counted. |
| Time Frame | 3, 6 and 12 months posttransplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population: all randomized and transplanted participants |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 50 | 48 | 49 | 53 | 50 |
| By 3 months; Indeterminate score |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| By 3 months; Mild Score |
14
28%
|
8
16.7%
|
7
14.3%
|
3
5.7%
|
7
14%
|
| By 3 months; Moderate Score |
3
6%
|
6
12.5%
|
7
14.3%
|
1
1.9%
|
2
4%
|
| By 3 months; Severe Score |
0
0%
|
1
2.1%
|
0
0%
|
0
0%
|
4
8%
|
| By 6 months; Indeterminate score |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| By 6 months; Mild Score |
17
34%
|
6
12.5%
|
7
14.3%
|
4
7.5%
|
8
16%
|
| By 6 months; Moderate Score |
3
6%
|
8
16.7%
|
8
16.3%
|
1
1.9%
|
3
6%
|
| By 6 months; Severe Score |
0
0%
|
1
2.1%
|
0
0%
|
0
0%
|
4
8%
|
| By 12 months; Indeterminate score |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| By 12 months; Mild Score |
17
34%
|
7
14.6%
|
7
14.3%
|
6
11.3%
|
8
16%
|
| By 12 months; Moderate Score |
4
8%
|
8
16.7%
|
9
18.4%
|
1
1.9%
|
3
6%
|
| By 12 months; Severe Score |
1
2%
|
1
2.1%
|
0
0%
|
0
0%
|
4
8%
|
| Title | Number of Participants Having Acute Rejection by Rejection Activity Index During the LTE |
|---|---|
| Description | Acute Rejections were clinically suspected and biopsy proven by central pathologist. The Banff Rejection Activity Index (RAI) comprises 3 components scored from 0 to 3: venous endothelial inflammation; bile duct inflammation damage; and portal inflammation; the scores are combined to an overall score (the RAI). An overall score of 0-2 is considered indeterminate, score of 3-4 is mild, score of 5-6 is moderate, and score of 7-9 is severe. Only the episode with the highest total RAI score for each participant was counted. |
| Time Frame | Day 1 (randomization) through End of study (database lock of 20-June-2011) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT-LTE population, all randomized and transplanted participants who entered the long-term extension phase. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 30 | 27 | 24 | 38 | 26 |
| By 12 months; Indeterminate score |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| By 12 months; Mild Score |
8
16%
|
5
10.4%
|
2
4.1%
|
5
9.4%
|
4
8%
|
| By 12 months; Moderate Score |
1
2%
|
1
2.1%
|
4
8.2%
|
1
1.9%
|
0
0%
|
| By 12 months; Severe Score |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
4%
|
| At end of study; Indeterminate score |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| At end of study; Mild Score |
8
16%
|
5
10.4%
|
2
4.1%
|
5
9.4%
|
4
8%
|
| At end of study; Moderate Score |
1
2%
|
1
2.1%
|
4
8.2%
|
1
1.9%
|
0
0%
|
| At end of study; Severe Score |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
4%
|
| Title | Number of Participants at Risk of First Acute Rejection as Determined by Kaplan-Meier Method by 12 Months |
|---|---|
| Description | The time from transplantation to the first AR episode in each treatment arm was summarized using Kaplan-Meier curves. Acute Rejections were clinically suspected and biopsy proven by central pathologist. |
| Time Frame | 3, 6, 9 and 12 months posttransplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population, all randomized and transplanted participants. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 50 | 48 | 49 | 53 | 50 |
| By 3 months |
30
60%
|
31
64.6%
|
30
61.2%
|
48
90.6%
|
34
68%
|
| By 6 months |
27
54%
|
29
60.4%
|
28
57.1%
|
47
88.7%
|
32
64%
|
| By 9 months |
25
50%
|
29
60.4%
|
27
55.1%
|
47
88.7%
|
32
64%
|
| By 12 months |
23
46%
|
25
52.1%
|
23
46.9%
|
42
79.2%
|
28
56%
|
| Title | Mean Change From Baseline in Measured Glomerular Filtration Rate (GFR): 12-month Treatment Phase |
|---|---|
| Description | GFR was assessed using a true measure of glomerular filtration via iothalamate clearance test. The month 2 time point was selected as the "baseline" time point with respect to measured GFR due to logistical difficulty in obtaining measured GFR at the time of liver transplant and post-transplant renal function largely stabilizing by 2 months. All Measured GFR > 200 were truncated at 200. |
| Time Frame | Baseline (2 month), 12 months posttransplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population: all randomized and transplanted subjects. n = participants who had both baseline and postbaseline values. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 50 | 48 | 49 | 53 | 50 |
| 2 months (n=37, 36, 35, 41, 37) |
72.4
(29.50)
|
86.6
(37.38)
|
98.6
(41.89)
|
65.9
(35.52)
|
58.5
(33.96)
|
| 12 months (n=39, 35, 29, 40, 32) |
88.9
(36.34)
|
93.1
(38.99)
|
73.1
(36.82)
|
75.2
(46.89)
|
70.5
(29.59)
|
| Change from 2 to 12 months (n=31, 29, 26, 36, 29) |
14.2
(40.64)
|
5.8
(48.20)
|
-19.6
(49.56)
|
5.3
(51.81)
|
7.3
(31.59)
|
| Title | Mean Change From Baseline in Calculated GFR, by Modification of Diet in Renal Disease (MDRD) Equation: 12-month Treatment Phase |
|---|---|
| Description | GFR is a measure of the rate at which blood is filtered by the kidney. MDRD is an equation (calculation) used to estimate GFR in participants with impaired renal function based on serum creatinine (ScR), age, race, gender, blood urea nitrogen (BUN), and albumin (Alb). GFR (mL/min/1.73 m^2) = 170*(Scr)^-0.999*(Age)^-0.176*(0.762 if female)*(1.180 if African American)*(BUN)^-0.170*(Alb)^+0.318. ). BL= baseline, mL= milliliters; min= minute; m^2= meters squared. |
| Time Frame | Baseline [BL] (pretransplant time point), 1, 2, 3, 6 and 12 months posttransplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population, all randomized and transplanted participants. n = participants who had both baseline and postbaseline values. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 50 | 48 | 49 | 53 | 50 |
| BL; (n=47, 42, 42, 45, 45) |
66.3
(29.14)
|
77.4
(33.42)
|
76.6
(27.77)
|
73.7
(32.42)
|
80.2
(30.78)
|
| 1 month; (n=45, 44, 42, 49, 49) |
85.6
(25.27)
|
93.1
(35.66)
|
89.6
(28.47)
|
64.9
(26.31)
|
62.2
(31.94)
|
| Change from BL to 1 month; (n=43, 38, 37, 41, 45) |
21.0
(33.76)
|
15.3
(44.72)
|
11.4
(31.34)
|
-8.7
(33.91)
|
-17.7
(40.65)
|
| 2 months; (n=29, 30, 23, 25, 27) |
86.1
(21.78)
|
96.6
(27.78)
|
105.8
(31.98)
|
76.3
(35.25)
|
66.9
(28.42)
|
| Change from BL to 2 months; (n=28, 26, 20, 22, 25) |
25.3
(32.35)
|
18.3
(33.35)
|
31.5
(26.89)
|
-1.5
(52.78)
|
-14.0
(34.03)
|
| 3 months; (n=36, 36, 35, 46, 37) |
86.5
(21.20)
|
91.7
(26.83)
|
96.6
(27.02)
|
65.0
(19.93)
|
60.4
(22.98)
|
| Change from BL to 3 months; (n=33, 34, 30, 40, 33) |
22.0
(29.04)
|
13.3
(31.50)
|
18.3
(26.92)
|
-8.4
(30.89)
|
-20.2
(32.08)
|
| 6 months; (n=39, 34, 38, 49, 36) |
82.2
(23.88)
|
90.3
(24.23)
|
86.0
(28.74)
|
61.9
(20.62)
|
59.8
(22.37)
|
| Change from BL to 6 months; (n=37, 30, 33, 42, 31) |
18.6
(31.06)
|
7.6
(31.43)
|
5.6
(26.78)
|
-11.7
(30.61)
|
-22.7
(29.63)
|
| 12 months; (n=40, 33, 35, 46, 38) |
83.8
(22.18)
|
97.7
(23.80)
|
85.6
(31.23)
|
68.4
(26.09)
|
63.8
(21.24)
|
| Change from BL to 12 month; (n=37, 29, 30, 41, 33) |
18.2
(27.63)
|
19.2
(30.05)
|
4.2
(30.40)
|
-6.3
(40.08)
|
-17.1
(28.61)
|
| Title | Mean Change From Baseline in Calculated GFR During the LTE |
|---|---|
| Description | GFR is a measure of the rate at which blood is filtered by the kidney. MDRD is an equation (calculation) used to estimate GFR in participants with impaired renal function based on serum creatinine (ScR), age, race, gender, blood urea nitrogen (BUN), and albumin (Alb). GFR (mL/min/1.73 m^2) = 170*(Scr)^-0.999*(Age)^-0.176*(0.762 if female)*(1.180 if African American)*(BUN)^-0.170*(Alb)^+0.318. ). BL= baseline, mL= milliliters; min= minute; m^2= meters squared. |
| Time Frame | Baseline (pretransplant time point), 1, 2, 3, 6,12, 18, 24, 30, 36 months posttransplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT-LTE population, all randomized and transplanted participants who entered long term extension. n= participants who have both baseline and postbaseline values. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 30 | 27 | 24 | 38 | 26 |
| Baseline (BL); (n=27,24,20,33,23) |
64.4
(32.98)
|
85.6
(34.74)
|
78.0
(31.65)
|
77.9
(32.13)
|
83.0
(35.80)
|
| 1 month; (n=28,27,23,36,25) |
88.2
(24.56)
|
103.1
(38.89)
|
95.1
(26.70)
|
68.6
(28.06)
|
59.1
(22.41)
|
| Change from BL to 1 month; (n=26,24,20,31,23) |
26.3
(30.52)
|
20.2
(52.60)
|
16.0
(31.53)
|
-7.6
(37.19)
|
-22.6
(25.62)
|
| 2 months; (n=21,21,15,19,19) |
86.2
(22.29)
|
99.4
(29.58)
|
102.3
(32.44)
|
71.2
(18.88)
|
64.4
(28.90)
|
| Change from BL to 2 months; (n=20,19,14,17,18) |
26.0
(34.74)
|
12.6
(30.12)
|
30.7
(29.13)
|
-11.6
(36.28)
|
-17.4
(33.94)
|
| 3 months; (n=27, 26, 24, 35, 24) |
87.0
(22.30)
|
97.0
(26.14)
|
97.0
(25.94)
|
66.5
(20.36)
|
57.0
(22.61)
|
| Change from BL to 3 months; (n=24, 24, 20, 30, 21) |
23.3
(32.20)
|
13.7
(32.38)
|
17.0
(27.99)
|
-8.1
(31.69)
|
-23.5
(30.57)
|
| 6 months; (n=29, 26, 24, 24, 38, 23) |
87.6
(23.93)
|
93.1
(23.45)
|
92.3
(24.71)
|
64.6
(20.43)
|
56.7
(20.37)
|
| Change from BL to 6 months; (n=27, 23, 20, 33, 20) |
24.0
(33.34)
|
8.6
(31.89)
|
12.2
(21.59)
|
-10.9
(30.53)
|
-23.3
(28.74)
|
| 12 months; (n=29, 25, 24, 36, 24) |
88.1
(21.45)
|
101.3
(25.01)
|
94.8
(27.89)
|
67.8
(22.07)
|
61.7
(20.49)
|
| Change from BL to 12 months; (n=26, 23, 20, 31,21) |
22.6
(29.57)
|
19.4
(30.28)
|
16.5
(24.91)
|
-9.3
(34.30)
|
-20.2
(27.65)
|
| 18 months; (n=24, 25, 21, 33, 21) |
84.8
(24.10)
|
95.0
(24.54)
|
91.3
(25.35)
|
69.0
(22.84)
|
63.2
(21.25)
|
| Change from BL to 18 months; (n=21, 23, 17, 28,18) |
22.5
(34.16)
|
11.2
(34.07)
|
7.4
(20.11)
|
-6.8
(31.26)
|
-6.1
(22.80)
|
| 24 months; (n=13, 15, 15, 22, 15) |
84.8
(26.18)
|
87.6
(21.43)
|
96.3
(26.02)
|
73.3
(22.82)
|
66.3
(21.63)
|
| Change from BL to 24 months; (n=10, 13, 11, 19,13) |
27.9
(33.76)
|
9.9
(37.62)
|
15.2
(19.64)
|
-2.2
(32.67)
|
2.3
(24.58)
|
| At 30 months; (n=6, 6, 6, 12, 7) |
102.9
(20.92)
|
94.4
(31.78)
|
90.4
(22.76)
|
64.1
(27.30)
|
59.5
(20.47)
|
| Change from BL to 30 months; (n=5, 5, 3, 8, 6) |
41.4
(33.98)
|
40.4
(38.10)
|
17.1
(26.76)
|
-15.0
(38.89)
|
-10.7
(13.40)
|
| Title | Mean Change From Baseline Serum Creatinine at Months 1, 2, 3, 6 and 12 |
|---|---|
| Description | Measurement of SCr is commonly used as an indicator of renal function. High creatinine blood level is an indicator of deficient filtering by the kidney. SCr was determined at baseline and various post-baseline time points. |
| Time Frame | Baseline (pretransplant time point), 1, 2, 3, 6 and 12 months posttransplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population, all randomized and transplanted participants. n= participants who have both baseline and postbaseline values. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 50 | 48 | 49 | 53 | 50 |
| Baseline (BL); (n=47, 42, 42, 45, 45) |
1.4
(1.25)
|
1.0
(0.39)
|
0.9
(0.38)
|
1.1
(0.54)
|
1.0
(0.40)
|
| At 1 months; (n=45, 44, 42, 49, 49) |
0.9
(0.38)
|
0.8
(0.32)
|
0.9
(0.42)
|
1.2
(0.41)
|
1.3
(0.68)
|
| Change from BL to 1 months; (n=43, 38, 37, 41, 45) |
-0.5
(1.35)
|
-0.1
(0.50)
|
-0.1
(0.48)
|
0.1
(0.52)
|
0.3
(0.75)
|
| At 2 months; (n=29, 30, 23, 25, 27) |
0.9
(0.21)
|
0.8
(0.22)
|
0.8
(0.28)
|
1.0
(0.30)
|
1.2
(0.36)
|
| Change from BL to 2 months; (n=28, 26, 20, 22, 25) |
-0.7
(1.54)
|
-0.2
(0.32)
|
-0.2
(0.32)
|
0.0
(0.73)
|
0.2
(0.45)
|
| At 3 months; (n=36, 36, 35, 46, 37) |
0.9
(0.27)
|
0.9
(0.21)
|
0.8
(0.24)
|
1.2
(0.36)
|
1.3
(0.53)
|
| Change from BL to 3 months; (n=33, 34, 30, 40, 33) |
-0.6
(1.45)
|
-0.1
(0.44)
|
-0.1
(0.32)
|
0.1
(0.50)
|
0.3
(0.42)
|
| At 6 months; (n=39, 34, 38, 49, 36) |
1.0
(0.30)
|
0.9
(0.20)
|
0.9
(0.42)
|
1.3
(0.44)
|
1.3
(0.51)
|
| Change from BL to 6 months; (n=37, 30, 33, 42, 31) |
-0.5
(1.39)
|
0.0
(0.41)
|
0.1
(0.43)
|
0.2
(0.60)
|
0.4
(0.50)
|
| At 12 months; (n=40, 33, 35, 46, 38) |
1.0
(0.26)
|
0.8
(0.16)
|
1.0
(0.37)
|
1.2
(0.49)
|
1.2
(0.32)
|
| Change from BL to 12 months; (n=37, 29, 30, 41,33) |
-0.5
(1.38)
|
-0.2
(0.42)
|
0.1
(0.47)
|
0.1
(0.63)
|
0.3
(0.33)
|
| Title | Mean Change in Baseline Values of Cystatin C at 2 and 12 Months |
|---|---|
| Description | Cystatin C is a protein encoded by the CST3 gene, which is mainly used as a biomarker of kidney function. If kidney function and glomerular filtration rate decline, the blood levels of cystatin C rise. |
| Time Frame | Baseline (pretransplant), 2, and 12 months posttransplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population: all randomized and transplanted participants. n = participants who had both baseline and postbaseline values. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 50 | 48 | 49 | 53 | 50 |
| Baseline (BL); (n=44, 47, 48, 49, 43) |
1.2
(0.64)
|
1.2
(0.57)
|
1.1
(0.39)
|
1.4
(0.73)
|
1.2
(0.60)
|
| 2 months; (n=40, 39, 39, 48, 43) |
1.1
(0.26)
|
1.1
(0.48)
|
1.0
(0.25)
|
1.4
(0.52)
|
1.5
(0.47)
|
| Change from BL to 2 months; (n=35, 38, 38, 44,37) |
-0.2
(0.62)
|
-0.1
(0.72)
|
-0.1
(0.31)
|
0.1
(0.77)
|
0.3
(0.70)
|
| 12 months; (n=40, 36, 36, 49, 40) |
1.1
(0.36)
|
0.9
(0.28)
|
1.2
(0.79)
|
1.3
(0.53)
|
1.3
(0.35)
|
| Change from BL to 12 months; (n=35, 35, 35,45,34) |
-0.2
(0.64)
|
-0.2
(0.63)
|
0.1
(0.86)
|
-0.1
(0.69)
|
0.1
(0.63)
|
| Title | Belatacept Pharmacokinetic (PK) Parameter: Maximum Serum Concentration |
|---|---|
| Description | Maximum Plasma Concentration (Cmax) is the maximum observed serum drug concentration. |
| Time Frame | Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received belatacept, and had complete PK profile. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 12 | 11 | 11 | 0 | 0 |
| Geometric Mean (Geometric Coefficient of Variation) [µg/mL] |
221.3
(29)
|
227.6
(23)
|
205.4
(20)
|
| Title | Belatacept Pharmacokinetic (PK) Parameter: Time to Achieve the Maximum Plasma Concentration |
|---|---|
| Description | Maximum Plasma Concentration (Tmax) is the time taken to reach the maximum observed plasma concentration. |
| Time Frame | Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received belatacept, and had complete PK profile. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 12 | 11 | 11 | 0 | 0 |
| Median (Full Range) [hour] |
1.00
|
1.08
|
1.00
|
| Title | Belatacept PK Parameter: Area Under the Serum Concentration-time Curve to the End of the Dosing Period (AUCtau) |
|---|---|
| Description | Area under the plasma concentration-time curve for each dosing interval is determined using the linear trapezoidal rule. The AUC(TAU) of belatacept from the MI regimens and LI regimens were calculated over 2 and 4 weeks respectively. |
| Time Frame | Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received belatacept, and had complete PK profile. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 10 | 5 | 6 | 0 | 0 |
| Geometric Mean (Geometric Coefficient of Variation) [µg*h/mL] |
19865
(21)
|
21526
(44)
|
19730
(22)
|
| Title | Belatacept PK Parameter: Minimum Plasma Concentration |
|---|---|
| Description | Minimum Plasma Concentration (Cmin) is the minimum observed serum drug concentration. |
| Time Frame | Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received belatacept, and had complete PK profile. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 13 | 11 | 12 | 0 | 0 |
| Geometric Mean (Geometric Coefficient of Variation) [µg/mL] |
23.63
(30)
|
27.20
(37)
|
5.91
(50)
|
| Title | Belatacept PK Parameter: Terminal Half-life |
|---|---|
| Description | Terminal Half-life (T 1/2) is the time a drug takes for the concentration levels to fall to 50% of their value. |
| Time Frame | Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received belatacept, and had complete PK profile. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 10 | 5 | 7 | 0 | 0 |
| Mean (Standard Deviation) [hour] |
240.80
(47.82)
|
227.74
(56.15)
|
207.88
(31.66)
|
| Title | Belatacept PK Parameter: Total Body Clearance |
|---|---|
| Description | Total body clearance is the rate and extent at which the drug is eliminated from the body. The clearance of a drug is used to understand the processes involved in drug elimination, distribution and metabolism. CLT was estimated from AUC (TAU) between Weeks 12 and 16, assuming steady state. |
| Time Frame | Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received belatacept, and had complete PK profile. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 10 | 5 | 6 | 0 | 0 |
| Geometric Mean (Geometric Coefficient of Variation) [mL/h/kg] |
0.45
(28)
|
0.41
(46)
|
0.45
(22)
|
| Title | Belatacept PK Parameter: Volume of Distribution |
|---|---|
| Description | Volume of distribution (Vss) is the volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration. . Vss was estimated from AUC (TAU) between Weeks 12 and 16, assuming steady state. |
| Time Frame | Samples were collected at Pre dose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received belatacept, and had complete PK profile. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 10 | 5 | 6 | 0 | 0 |
| Mean (Standard Deviation) [L/kg] |
0.09
(0.02)
|
0.08
(0.04)
|
0.11
(0.03)
|
| Title | Belatacept PK Parameter: Amount Excreted in Ascites Fluid Over Days 1 to 14 |
|---|---|
| Description | Amount Excreted in Ascites (Ae,asc) was estimated from the ascites drug concentrations and volumes within a dosing interval. |
| Time Frame | Days 1 to 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received belatacept, and had complete PK profile. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 8 | 8 | 12 | 0 | 0 |
| Mean (Standard Deviation) [µg] |
46654
(59210)
|
31425
(40382)
|
81451
(95931)
|
| Title | Belatacept PK Parameter: Clearance From Ascites Fluid |
|---|---|
| Description | Clearance from ascites fluid was determined by amount excreted in ascites fluid (Ae, asc)[0-T] / AUC[0-T], where 0-T is the same duration relative to a belatacept infusion. |
| Time Frame | Days 1 to 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Serum AUC was not available for the time interval corresponding to ascites fluid collection. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 0 | 0 | 0 | 0 | 0 |
| Title | Belatacept Trough Concentration Before Each Infusion During the LTE |
|---|---|
| Description | Minimum Plasma Concentration (Cmin) is the minimum observed serum drug concentration. |
| Time Frame | Samples were collected predose on Days 5, 14, 28, 56, 84, 112, 168, 252, 336, 364; after end of infusion on Days 1, 5, 84, 112, 196, 336; and on Days 9, 85, 91, 98, 105, 532, 728. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received Belatacept, and had complete PK profile. n= participants with values at all time points. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 50 | 48 | 49 | 0 | 0 |
| Day 5: (n=40, 43, 41) |
79.15
(33.32)
|
79.40
(33.19)
|
70.88
(38.66)
|
||
| Day 14: (n=41, 43, 38) |
32.39
(40.85)
|
31.16
(39.74)
|
29.21
(47.62)
|
||
| Day 28: (n=42, 38, 37) |
23.51
(46.71)
|
22.23
(47.49)
|
21.72
(47.64)
|
||
| Day 56: (n=12, 13, 12) |
18.91
(39.74)
|
18.84
(36.85)
|
6.57
(82.41)
|
||
| Day 84: (n=34, 31, 34 ) |
27.11
(38.29)
|
27.32
(56.13)
|
6.60
(54.25)
|
||
| Day 112: (n=29, 26, 29) |
10.12
(63.71)
|
9.64
(59.28)
|
6.75
(64.11)
|
||
| Day 168: (n=30, 29, 29) |
7.30
(58.14)
|
8.01
(64.97)
|
3.57
(52.56)
|
||
| Day 252: (n=28, 28, 27) |
3.65
(67.07)
|
3.74
(65.78)
|
3.59
(50.93)
|
||
| Day 336: (n=26, 23, 21) |
3.22
(70.42)
|
3.38
(62.10)
|
4.37
(29.72)
|
||
| Day 364: (n=28, 28, 22 ) |
2.52
(70.82)
|
4.01
(55.68)
|
3.62
(48.17)
|
||
| Day 532: (n=22, 24, 14) |
2.71
(55.53)
|
4.68
(57.61)
|
4.91
(34.49)
|
||
| Day 728: (n=10, 12, 14) |
4.75
(53.56)
|
4.20
(59.28)
|
4.22
(46.73)
|
| Title | Percentage of Participants (Who Were Hepatitis C Virus [HCV] Positive at Baseline) With HCV Recurrence (Assessed by Central Pathologist) by 12 Months |
|---|---|
| Description | HCV Recurrence is defined as Histological confirmation on liver biopsy by the Ishak (modified Knodell) system and required both a score >= 5 out of 18 on modified Histological Activity Index grading and a fibrosis Score >= 2 out of 6 on modified staging. All biopsies, including Week 52 biopsies, were considered. Only the first HCV recurrence episode for each participant was counted. For 95% CI within each group, normal approximation was used if N>=5, otherwise exact method was used. For 95% CI of difference, normal approximation was used if N>=5 in both arms, otherwise exact method was used. |
| Time Frame | 6 and 12 months posttransplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population, all randomized and transplanted participants. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept Less Intensive (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab ; Intravenous (IV), 20 mg, Day 1 and Day 5 Belatacept More Intensive (MI) ; Intravenous (IV), 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF), Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (Short term [ST]), ≤ 1 g/day, 4 years (Long-term extension [LTE]) | Belatacept More Intensive (MI): IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF , Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Drug: Belatacept Less Intensive (LI), IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (Short Term [ST]), in accordance with local practice and the package insert, 4 years (LTE) + MMF, IV/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE) |
| Measure Participants | 23 | 23 | 21 | 25 | 24 |
| 6 months |
39.1
78.2%
|
21.7
45.2%
|
23.8
48.6%
|
20.0
37.7%
|
33.3
66.6%
|
| 12 months |
60.9
121.8%
|
30.4
63.3%
|
28.6
58.4%
|
52.0
98.1%
|
37.5
75%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 6 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 19.1 | |
| Confidence Interval |
(2-Sided) 95% -6.7 to 43.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 6 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 1.7 | |
| Confidence Interval |
(2-Sided) 95% -21.6 to 25.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 6 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 3.8 | |
| Confidence Interval |
(2-Sided) 95% -20.1 to 28.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 6 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 5.8 | |
| Confidence Interval |
(2-Sided) 95% -21.2 to 32.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 6 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -11.6 | |
| Confidence Interval |
(2-Sided) 95% -36.0 to 14.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 6 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -9.5 | |
| Confidence Interval |
(2-Sided) 95% -34.6 to 17.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 8.9 | |
| Confidence Interval |
(2-Sided) 95% -18.8 to 35.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -21.6 | |
| Confidence Interval |
(2-Sided) 95% -46.3 to 6.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -23.4 | |
| Confidence Interval |
(2-Sided) 95% -48.2 to 5.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 23.4 | |
| Confidence Interval |
(2-Sided) 95% -5.2 to 48.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -7.1 | |
| Confidence Interval |
(2-Sided) 95% -32.9 to 19.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -8.9 | |
| Confidence Interval |
(2-Sided) 95% -34.8 to 18.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
| Title | Percentage of Participants (Who Were Hepatitis C Virus [HCV] Positive at Baseline) With HCV Recurrence (Assessed by Central Pathologist) During the LTE |
|---|---|
| Description | HCV Recurrence is defined as Histological confirmation on liver biopsy by the Ishak (modified Knodell) system and required both a score >= 5 out of 18 on modified Histological Activity Index grading and a fibrosis Score >= 2 out of 6 on modified staging. All biopsies, including Week 52 biopsies, were considered. Only the first HCV recurrence episode for each participant was counted. For 95% CI within each group, normal approximation was used if N>=5, otherwise exact method was used. For 95% CI of difference, normal approximation was used if N>=5 in both arms, otherwise exact method was used. |
| Time Frame | 12 months posttransplant, end of study (database lock, 20-June-2011) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT-LTE population, all randomized and transplanted participants who entered long-term extension. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept Less Intensive (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab ; Intravenous (IV), 20 mg, Day 1 and Day 5 Belatacept More Intensive (MI) ; Intravenous (IV), 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF), Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (Short term [ST]), ≤ 1 g/day, 4 years (Long-term extension [LTE]) | Belatacept More Intensive (MI): IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF , Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Drug: Belatacept Less Intensive (LI), IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (Short Term [ST]), in accordance with local practice and the package insert, 4 years (LTE) + MMF, IV/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE) |
| Measure Participants | 12 | 12 | 9 | 17 | 11 |
| At 12 months |
50.0
100%
|
41.7
86.9%
|
0
0%
|
58.8
110.9%
|
72.7
145.4%
|
| At end of study |
66.7
133.4%
|
50.0
104.2%
|
22.2
45.3%
|
64.7
122.1%
|
72.7
145.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -8.8 | |
| Confidence Interval |
(2-Sided) 95% -42.4 to 26.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N >= 5 in each treatment arm. Otherwise exact method was used. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -17.2 | |
| Confidence Interval |
(2-Sided) 95% -49.2 to 19.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N >= 5 in each treatment arm. Otherwise exact method was used. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -58.8 | |
| Confidence Interval |
(2-Sided) 95% -81.6 to -19.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N >= 5 in each treatment arm. Otherwise exact method was used. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -22.7 | |
| Confidence Interval |
(2-Sided) 95% -55.9 to 16.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N >= 5 in each treatment arm. Otherwise exact method was used. | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -31.1 | |
| Confidence Interval |
(2-Sided) 95% -62.6 to 9.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N >= 5 in each treatment arm. Otherwise exact method was used. | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -72.7 | |
| Confidence Interval |
(2-Sided) 95% -94.0 to -33.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N >= 5 in each treatment arm. Otherwise exact method was used. | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at database lock | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 2.0 | |
| Confidence Interval |
(2-Sided) 95% -32.6 to 34.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N >= 5 in each treatment arm. Otherwise exact method was used. | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at database lock | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -14.7 | |
| Confidence Interval |
(2-Sided) 95% -47.4 to 20.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N >= 5 in each treatment arm. Otherwise exact method was used. | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at database lock | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -42.5 | |
| Confidence Interval |
(2-Sided) 95% -72.6 to 0.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N >= 5 in each treatment arm. Otherwise exact method was used. | |
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at database lock | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -6.1 | |
| Confidence Interval |
(2-Sided) 95% -41.1 to 31.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N >= 5 in each treatment arm. Otherwise exact method was used. | |
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at database lock | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -22.7 | |
| Confidence Interval |
(2-Sided) 95% -55.9 to 16.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N >= 5 in each treatment arm. Otherwise exact method was used. | |
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at database lock | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -50.5 | |
| Confidence Interval |
(2-Sided) 95% -81.9 to -3.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, normal approximation was used if N >= 5 in each treatment arm. Otherwise exact method was used. | |
| Title | Number of Participants (Who Were HCV Positive at Baseline) With HCV Ribonucleic Acid (RNA) Levels >2.4*10^6 U/mL and >4.7*10^6 U/mL: 12-month Treatment Phase |
|---|---|
| Description | Recurrent hepatitis C infection of the allograft following liver transplantation can be detected by monitoring HCV RNA levels. In HCV positive participants, quantitative HCV RNA levels > 2.4 * 10^6 U/mL and > 4.7 * 10^6 U/mL were descriptively summarized by treatment group. BL=baseline |
| Time Frame | Baseline (pretransplant), 6 and 12 months (mo) posttransplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population, all randomized and transplanted participants. n= participants who were HCV positive at baseline. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept Less Intensive (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab ; Intravenous (IV), 20 mg, Day 1 and Day 5 Belatacept More Intensive (MI) ; Intravenous (IV), 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF), Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (Short term [ST]), ≤ 1 g/day, 4 years (Long-term extension [LTE]) | Belatacept More Intensive (MI): IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF , Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Drug: Belatacept Less Intensive (LI), IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (Short Term [ST]), in accordance with local practice and the package insert, 4 years (LTE) + MMF, IV/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE) |
| Measure Participants | 23 | 23 | 21 | 25 | 24 |
| BL; HCV RNA > 2.4*10^6 U/mL (n=21,22,19,22,23) |
2
4%
|
4
8.3%
|
2
4.1%
|
3
5.7%
|
1
2%
|
| BL; HCV RNA > 4.7 *10^6 U/mL (n=21,22,19,22,23) |
0
0%
|
1
2.1%
|
1
2%
|
0
0%
|
0
0%
|
| 6 mo; HCV RNA > 2.4*10^6 U/mL (n=16,15,15,21,14) |
9
18%
|
7
14.6%
|
8
16.3%
|
14
26.4%
|
11
22%
|
| 6 mo; HCV RNA > 4.7*10^6 U/mL (n=16,15,15,21,14) |
7
14%
|
7
14.6%
|
7
14.3%
|
11
20.8%
|
10
20%
|
| 12 mo; HCV RNA > 2.4*10^6 U/mL (n=15,13,14,20,13) |
7
14%
|
7
14.6%
|
7
14.3%
|
13
24.5%
|
7
14%
|
| 12 mo; HCV RNA > 4.7*10^6 U/mL (n=15,13,14,20,13) |
6
12%
|
6
12.5%
|
5
10.2%
|
11
20.8%
|
7
14%
|
| Title | Number of Participants (Who Were HCV Positive at Baseline) With HCV RNA Levels >2.4 * 10^6 U/mL and >4.7 * 10^6 U/mL During the LTE |
|---|---|
| Description | Recurrent hepatitis C infection of the allograft following liver transplantation can be detected by monitoring HCV RNA levels. In HCV positive participants, quantitative HCV RNA levels > 2.4 x 10^6 U/mL and > 4.7 x 10^6 U/mL were descriptively summarized by treatment group. BL = baseline |
| Time Frame | BL (pretransplant), 12, 18, 24, 30 months (mo) posttransplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT-LTE population, all randomized and transplanted participants. n= participants with HCV RNA values. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept Less Intensive (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab ; Intravenous (IV), 20 mg, Day 1 and Day 5 Belatacept More Intensive (MI) ; Intravenous (IV), 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF), Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (Short term [ST]), ≤ 1 g/day, 4 years (Long-term extension [LTE]) | Belatacept More Intensive (MI): IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF , Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Drug: Belatacept Less Intensive (LI), IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (Short Term [ST]), in accordance with local practice and the package insert, 4 years (LTE) + MMF, IV/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE) |
| Measure Participants | 12 | 12 | 9 | 17 | 11 |
| BL; HCV RNA > 2.4*10^6 U/mL (n=10,11,6,15,10) |
0
0%
|
1
2.1%
|
0
0%
|
2
3.8%
|
1
2%
|
| 12 mo; HCV RNA > 2.4*10^6 U/mL (n=11,10,8,16,10) |
6
12%
|
5
10.4%
|
4
8.2%
|
10
18.9%
|
4
8%
|
| 12 mo; HCV RNA > 4.7*10^6 U/mL (n=11,10,8,16,10) |
6
12%
|
4
8.3%
|
3
6.1%
|
8
15.1%
|
4
8%
|
| 18 mo; HCV RNA > 2.4*10^6 U/mL (n=7,10,3,12,9) |
3
6%
|
2
4.2%
|
2
4.1%
|
7
13.2%
|
3
6%
|
| 18 mo; HCV RNA > 4.7*10^6 U/mL (n=7,10,3,12,9) |
2
4%
|
2
4.2%
|
2
4.1%
|
6
11.3%
|
2
4%
|
| 24 mo; HCV RNA > 2.4*10^6 U/mL (n=4,3,4,8,4) |
2
4%
|
1
2.1%
|
1
2%
|
6
11.3%
|
1
2%
|
| 24 mo; HCV RNA > 4.7*10^6 U/mL (n=4,3,4,8,4) |
2
4%
|
0
0%
|
0
0%
|
5
9.4%
|
1
2%
|
| 30 mo; HCV RNA > 2.4*10^6 U/mL (n=1,1,1,2,2) |
1
2%
|
0
0%
|
0
0%
|
1
1.9%
|
1
2%
|
| 30 mo; HCV RNA > 4.7*10^6 U/mL (n=1,1,1,2,2) |
1
2%
|
0
0%
|
0
0%
|
1
1.9%
|
1
2%
|
| Title | Percentage of Participants Who Develop Dyslipidemia, Hypertriglyceridemia and Hypercholesterolemia After Randomization and Transplantation: 12-month Treatment Phase |
|---|---|
| Description | Percentage of participants who develop dyslipidemia, defined as hypertriglyceridemia (triglycerides [TGs] ≥ 500 mg/dL [5.65 mmol/L]), hypercholesterolemia (Low density lipoprotein [LDL] ≥ 100 mg/dL [2.59 mmol/L]), or elevated non-high density lipoprotein (non- high density lipoprotein [HDL] ≥ 130 mg/dL [3.36 mmol/L]) in the presence of high TGs (TGs ≥ 200 mg/dL [2.26 mmol/L]). |
| Time Frame | 6 and 12 months posttransplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population, all randomized and transplanted participants who did not have dyslipidemia at baseline |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept Less Intensive (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab ; Intravenous (IV), 20 mg, Day 1 and Day 5 Belatacept More Intensive (MI) ; Intravenous (IV), 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF), Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (Short term [ST]), ≤ 1 g/day, 4 years (Long-term extension [LTE]) | Belatacept More Intensive (MI): IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF , Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Drug: Belatacept Less Intensive (LI), IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (Short Term [ST]), in accordance with local practice and the package insert, 4 years (LTE) + MMF, IV/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE) |
| Measure Participants | 42 | 35 | 46 | 42 | 37 |
| By 6 month: Dyslipidemia |
50.0
100%
|
54.3
113.1%
|
45.7
93.3%
|
33.3
62.8%
|
59.5
119%
|
| By 6 month: Hypertriglyceridemia |
2.4
4.8%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| By 6 month: Hypercholesterolemia |
42.9
85.8%
|
48.6
101.3%
|
39.1
79.8%
|
28.6
54%
|
51.4
102.8%
|
| By 12 month: Dyslipidemia |
59.5
119%
|
57.1
119%
|
58.7
119.8%
|
50.0
94.3%
|
70.3
140.6%
|
| By 12 month: Hypertriglyceridemia |
4.8
9.6%
|
0
0%
|
2.2
4.5%
|
2.4
4.5%
|
0
0%
|
| By 12 month: Hypercholesterolemia |
54.8
109.6%
|
54.3
113.1%
|
52.2
106.5%
|
42.9
80.9%
|
62.2
124.4%
|
| Title | Percentage of Participants Meeting the Definition of Dyslipidemia, Hypertriglyceridemia or Hypercholesterolemia at Any Given Time: 12-month Treatment Phase |
|---|---|
| Description | Percentage of participants at any given time (at Month 6 and Month 12) who met the definition of dyslipidemia.Dyslipidemia is defined as hypertriglyceridemia (TGs ≥ 500 mg/dL [5.65 mmol/L]), hypercholesterolemia (LDL ≥ 100 mg/dL [2.59 mmol/L]), or elevated non-HDL (non-HDL ≥ 130 mg/dL [3.36 mmol/L]) in the presence of high TGs (TGs ≥ 200 mg/dL [2.26 mmol/L]). |
| Time Frame | 6 and 12 months posttransplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population, all randomized and transplanted participants. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept Less Intensive (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab ; Intravenous (IV), 20 mg, Day 1 and Day 5 Belatacept More Intensive (MI) ; Intravenous (IV), 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF), Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (Short term [ST]), ≤ 1 g/day, 4 years (Long-term extension [LTE]) | Belatacept More Intensive (MI): IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF , Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Drug: Belatacept Less Intensive (LI), IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (Short Term [ST]), in accordance with local practice and the package insert, 4 years (LTE) + MMF, IV/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE) |
| Measure Participants | 50 | 48 | 49 | 53 | 50 |
| 6 months: Dyslipidemia |
36.0
72%
|
31.3
65.2%
|
30.6
62.4%
|
32.1
60.6%
|
26.0
52%
|
| 6 months: Hypertriglyceridemia |
6.0
12%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| 6 months: Hypercholesterolemia |
30.0
60%
|
29.2
60.8%
|
24.5
50%
|
30.2
57%
|
22.0
44%
|
| 12 months: Dyslipidemia |
40.0
80%
|
33.3
69.4%
|
44.9
91.6%
|
34.0
64.2%
|
42.0
84%
|
| 12 months: Hypertriglyceridemia |
4.0
8%
|
0
0%
|
2.0
4.1%
|
1.9
3.6%
|
2.0
4%
|
| 12 months: Hypercholesterolemia |
30.0
60%
|
29.2
60.8%
|
40.8
83.3%
|
30.2
57%
|
36.0
72%
|
| Title | Summary Statistics for Lipid Parameters-Serum Total Non-High Density Lipoprotein (Non-HDL) Cholesterol: 12-month Treatment Phase |
|---|---|
| Description | |
| Time Frame | Baseline (pretransplant), 1, 6, 12 months posttransplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population, all randomized and transplanted participants. n = participants who had both baseline and postbaseline values. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept Less Intensive (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab ; Intravenous (IV), 20 mg, Day 1 and Day 5 Belatacept More Intensive (MI) ; Intravenous (IV), 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF), Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (Short term [ST]), ≤ 1 g/day, 4 years (Long-term extension [LTE]) | Belatacept More Intensive (MI): IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF , Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Drug: Belatacept Less Intensive (LI), IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (Short Term [ST]), in accordance with local practice and the package insert, 4 years (LTE) + MMF, IV/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE) |
| Measure Participants | 50 | 48 | 49 | 53 | 50 |
| BL (n=45, 42, 44, 49, 46) |
80.4
(37.1)
|
83.5
(44.2)
|
84.8
(60.76)
|
77.7
(44.30)
|
76.8
(46.85)
|
| 1 months (n=46, 47, 42, 49, 49) |
125.1
(42.91)
|
147.9
(82.96)
|
148.0
(71.11)
|
121.7
(40.25)
|
130.0
(50.75)
|
| Change from BL to 1 months (n=42, 41, 39, 45, 45) |
47.2
(50.14)
|
66.0
(102.0)
|
54.1
(86.63)
|
47.0
(61.36)
|
47.5
(50.32)
|
| 6 months (n=39, 34, 38, 48, 36) |
139.3
(48.93)
|
134.4
(45.16)
|
138.9
(43.39)
|
125.1
(44.02)
|
135.4
(58.49)
|
| Change from BL to 6 months (n=35, 30, 35, 44, 32) |
59.5
(48.06)
|
44.0
(54.37)
|
48.2
(75.74)
|
48.1
(51.09)
|
48.6
(76.78)
|
| 12 months (n=40, 33, 35, 45, 37) |
143.2
(84.77)
|
137.4
(38.49)
|
142.2
(62.41)
|
118.2
(43.00)
|
131.9
(39.71)
|
| Change from BL to 12 months (n=35, 29, 32, 42, 33) |
66.7
(80.64)
|
49.2
(63.87)
|
53.4
(97.28)
|
47.4
(54.80)
|
44.1
(72.35)
|
| Title | Summary Statistics for Lipid Parameters; Serum HDL Cholesterol: 12-month Treatment Phase |
|---|---|
| Description | |
| Time Frame | Baseline (pretransplant), 1, 6, 12 months posttransplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population, all randomized and transplanted participants. n = participants who had both baseline and postbaseline values. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept Less Intensive (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab ; Intravenous (IV), 20 mg, Day 1 and Day 5 Belatacept More Intensive (MI) ; Intravenous (IV), 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF), Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (Short term [ST]), ≤ 1 g/day, 4 years (Long-term extension [LTE]) | Belatacept More Intensive (MI): IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF , Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Drug: Belatacept Less Intensive (LI), IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (Short Term [ST]), in accordance with local practice and the package insert, 4 years (LTE) + MMF, IV/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE) |
| Measure Participants | 50 | 48 | 49 | 53 | 50 |
| BL (n=46, 42, 44, 49, 46) |
32.1
(17.38)
|
36.2
(17.49)
|
36.5
(19.66)
|
33.3
(21.97)
|
31.1
(15.50)
|
| 1 month (n=46, 47, 42, 49, 49) |
41.3
(15.37)
|
36.9
(17.80)
|
42.5
(19.60)
|
41.2
(11.32)
|
34.1
(14.11)
|
| Change from BL to 1month (n=43, 41, 39, 45, 45) |
9.9
(26.83)
|
1.7
(26.15)
|
7.2
(27.72)
|
7.1
(22.65)
|
3.4
(21.37)
|
| 6 months (n=39, 34, 38, 48, 36) |
41.5
(14.29)
|
42.8
(14.17)
|
44.2
(14.56)
|
45.5
(15.80)
|
42.6
(17.92)
|
| Change from BL to 6 months (n=36, 30, 35, 44, 32) |
9.2
(21.56)
|
7.3
(20.40)
|
9.4
(22.06)
|
10.8
(28.26)
|
9.5
(24.32)
|
| 12 months (n=40, 33, 35, 45, 37) |
43.6
(14.40)
|
41.5
(15.19)
|
44.2
(14.37)
|
45.6
(15.35)
|
43.3
(15.58)
|
| Change from BL to12 months (n=36, 29, 32, 42, 33) |
12.7
(23.25)
|
8.3
(22.75)
|
7.3
(24.71)
|
10.9
(24.13)
|
10.0
(21.01)
|
| Title | Summary Statistics for Lipid Parameters- Serum Low Density Lipoprotein Cholesterol (LDL): 12-month Treatment Phase |
|---|---|
| Description | |
| Time Frame | Baseline (pretransplant), 1, 6, 12 months posttransplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population, all randomized and transplanted participants. n = participants who had both baseline and postbaseline values. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept Less Intensive (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab ; Intravenous (IV), 20 mg, Day 1 and Day 5 Belatacept More Intensive (MI) ; Intravenous (IV), 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF), Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (Short term [ST]), ≤ 1 g/day, 4 years (Long-term extension [LTE]) | Belatacept More Intensive (MI): IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF , Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Drug: Belatacept Less Intensive (LI), IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (Short Term [ST]), in accordance with local practice and the package insert, 4 years (LTE) + MMF, IV/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE) |
| Measure Participants | 50 | 48 | 49 | 53 | 50 |
| BL (n=29, 30, 25, 34, 32) |
52.3
(25.26)
|
58.6
(34.97)
|
58.9
(34.08)
|
63.6
(45.02)
|
59.9
(42.60)
|
| 1 month (n=30, 34, 29, 41, 42) |
95.2
(33.82)
|
93.2
(33.73)
|
115.7
(58.88)
|
89.8
(37.31)
|
98.4
(47.68)
|
| Change from BL to 1 month (n=17, 21, 17, 27, 30) |
42.7
(47.94)
|
34.3
(48.98)
|
57.1
(30.19)
|
26.1
(48.40)
|
41.5
(43.68)
|
| 6 months (n=27, 29, 27, 41, 30) |
99.2
(36.93)
|
107.5
(36.93)
|
98.2
(42.85)
|
96.7
(42.22)
|
92.8
(29.03)
|
| Change from BL to 6 months (n=16, 19, 18, 28, 22) |
41.2
(33.82)
|
45.9
(42.13)
|
48.7
(41.66)
|
28.9
(49.29)
|
26.1
(54.04)
|
| 12 months (n=38, 29, 32, 42, 35) |
93.0
(30.72)
|
107.2
(32.75)
|
103.2
(36.41)
|
89.0
(37.15)
|
93.8
(27.45)
|
| Change from BL to 12 months (n=22, 19, 20, 25, 22) |
37.8
(33.09)
|
45.4
(51.75)
|
37.2
(47.81)
|
23.7
(46.80)
|
13.7
(50.98)
|
| Title | Summary Statistics for Lipid Parameters- Serum Cholesterol: 12-month Treatment Phase |
|---|---|
| Description | |
| Time Frame | Baseline (pretransplant), 1, 6, 12 months posttransplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population, all randomized and transplanted participants. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept Less Intensive (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab ; Intravenous (IV), 20 mg, Day 1 and Day 5 Belatacept More Intensive (MI) ; Intravenous (IV), 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF), Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (Short term [ST]), ≤ 1 g/day, 4 years (Long-term extension [LTE]) | Belatacept More Intensive (MI): IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF , Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Drug: Belatacept Less Intensive (LI), IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (Short Term [ST]), in accordance with local practice and the package insert, 4 years (LTE) + MMF, IV/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE) |
| Measure Participants | 50 | 48 | 49 | 53 | 50 |
| BL (n=45, 42, 44, 49, 47) |
112.9
(49.76)
|
119.7
(51.81)
|
121.3
(63.05)
|
111.0
(54.91)
|
106.4
(51.82)
|
| 1 month (n=46, 47, 42, 49, 49) |
166.3
(45.92)
|
184.9
(77.16)
|
190.6
(69.54)
|
162.9
(43.72)
|
164.1
(52.95)
|
| Change from BL to 1 month (n=42, 41, 39, 45, 46) |
57.0
(63.06)
|
67.7
(102.3)
|
61.3
(84.20)
|
54.0
(70.01)
|
53.4
(57.19)
|
| 6 months (n=39, 34, 38, 48, 36) |
180.8
(52.76)
|
177.3
(49.56)
|
182.2
(45.58)
|
170.6
(49.30)
|
177.9
(57.92)
|
| Change from BL to 6 months (n=35, 30, 35, 44, 33) |
68.6
(60.07)
|
51.3
(63.22)
|
56.6
(72.89)
|
58.9
(66.3)
|
60.8
(71.33)
|
| 12 months (n=40, 33, 35, 45, 37) |
186.8
(87.16)
|
178.9
(42.13)
|
186.4
(59.11)
|
163.8
(46.41)
|
175.2
(38.37)
|
| Change from BL to 12 months (n=35, 29,32, 42, 34) |
79.4
(86.88)
|
57.5
(73.67)
|
60.7
(92.87)
|
58.2
(64.05)
|
57.3
(72.22)
|
| Title | Summary Statistics for Lipid Parameters - Serum Triglyceride: 12-month Treatment Phase |
|---|---|
| Description | |
| Time Frame | Baseline (pretransplant), 1, 6, 12 months posttransplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population, all randomized and transplanted participants. n = participants who had both baseline and postbaseline values. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept Less Intensive (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab ; Intravenous (IV), 20 mg, Day 1 and Day 5 Belatacept More Intensive (MI) ; Intravenous (IV), 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF), Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (Short term [ST]), ≤ 1 g/day, 4 years (Long-term extension [LTE]) | Belatacept More Intensive (MI): IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF , Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Drug: Belatacept Less Intensive (LI), IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (Short Term [ST]), in accordance with local practice and the package insert, 4 years (LTE) + MMF, IV/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE) |
| Measure Participants | 50 | 48 | 49 | 53 | 50 |
| BL (n=29, 30, 25, 34, 32) |
94.4
(60.42)
|
110.1
(135.1)
|
80.2
(46.29)
|
84.4
(34.22)
|
89.2
(73.45)
|
| 1 month (n=29, 33, 29, 41, 43) |
153.9
(65.83)
|
162.9
(108.1)
|
149.0
(72.84)
|
149.1
(61.27)
|
163.5
(73.80)
|
| Change from BL to 1 month (n=16, 20, 17, 27, 30) |
71.2
(84.87)
|
45.7
(223.0)
|
85.8
(93.63)
|
68.2
(75.45)
|
71.8
(58.66)
|
| 6 months (n=26, 29, 25, 41, 30) |
234.3
(316.6)
|
157.1
(82.23)
|
162.7
(109.2)
|
148.1
(67.50)
|
167.2
(100.8)
|
| Change from BL to 6 months (n=15, 19, 18, 28, 22) |
199.9
(329.1)
|
18.3
(140.8)
|
88.7
(113.1)
|
60.8
(63.06)
|
84.3
(105.2)
|
| 12 months (n=38, 29, 32, 42, 34) |
255.1
(582.7)
|
159.0
(70.77)
|
158.2
(99.93)
|
156.4
(105.7)
|
190.5
(125.7)
|
| Change from BL to 12 months (n=22, 19, 20, 25, 21) |
237.2
(703.9)
|
20.3
(180.9)
|
91.6
(118.0)
|
72.3
(60.61)
|
92.6
(116.4)
|
| Title | Summary Statistics for Systolic Blood Pressure: 12-month Treatment Phase |
|---|---|
| Description | |
| Time Frame | Baseline (pretransplant), 1, 3, 6, 9, 12 months posttransplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population, all randomized and transplanted participants. n = participants who had both baseline and postbaseline values. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept Less Intensive (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab ; Intravenous (IV), 20 mg, Day 1 and Day 5 Belatacept More Intensive (MI) ; Intravenous (IV), 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF), Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (Short term [ST]), ≤ 1 g/day, 4 years (Long-term extension [LTE]) | Belatacept More Intensive (MI): IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF , Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Drug: Belatacept Less Intensive (LI), IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (Short Term [ST]), in accordance with local practice and the package insert, 4 years (LTE) + MMF, IV/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE) |
| Measure Participants | 50 | 48 | 49 | 53 | 50 |
| BL (n=50, 48, 49, 53, 49) |
115.3
(18.41)
|
115.4
(22.35)
|
111.4
(15.80)
|
121.2
(17.31)
|
125.3
(21.87)
|
| 1 month (n=50, 48, 49, 52, 48) |
123.3
(16.87)
|
126.3
(15.44)
|
120.9
(16.96)
|
129.2
(13.79)
|
124.6
(16.41)
|
| Change from BL to 1 month (n=50, 48, 49, 52, 47) |
8.0
(19.95)
|
10.9
(27.03)
|
9.4
(21.65)
|
8.5
(18.43)
|
0.6
(24.26)
|
| 3 months (n=44, 46, 41, 48, 42) |
127.0
(15.04)
|
126.9
(15.03)
|
124.4
(17.65)
|
136.9
(18.61)
|
133.0
(16.18)
|
| Change from BL to 3 months (n=44, 46, 41, 48, 41) |
10.9
(23.10)
|
11.7
(23.85)
|
12.7
(21.30)
|
16.3
(24.64)
|
9.1
(24.99)
|
| 6 months (n=43, 40, 36, 47, 37) |
124.0
(16.09)
|
126.5
(15.87)
|
124.6
(14.75)
|
130.6
(23.29)
|
132.0
(22.11)
|
| Change from BL to 6 months (n=43, 40, 36, 47, 36) |
8.4
(23.18)
|
9.3
(24.44)
|
12.8
(19.77)
|
10.0
(26.62)
|
8.3
(27.45)
|
| 9 months (n=34, 30, 29, 41, 31) |
125.5
(16.24)
|
125.8
(13.16)
|
123.9
(12.22)
|
135.6
(20.81)
|
133.9
(15.58)
|
| Change from BL to 9 months (n=34, 30, 29, 41, 31) |
10.4
(21.36)
|
8.8
(29.71)
|
13.3
(21.94)
|
14.4
(26.73)
|
11.6
(20.39)
|
| 12 months (n=42, 37, 36, 46, 38) |
125.8
(12.79)
|
127.0
(17.02)
|
121.2
(13.06)
|
137.0
(18.09)
|
138.0
(18.67)
|
| Change from BL to 12 months (n=42, 37, 36, 46, 37) |
9.2
(22.96)
|
10.2
(27.33)
|
10.6
(17.46)
|
15.9
(25.60)
|
14.6
(25.88)
|
| Title | Summary Statistics for Diastolic Blood Pressure: 12-month Treatment Phase |
|---|---|
| Description | Participants were considered to have hypertension if they had Diastolic Blood Pressure (SBP) ≥ 80 mmHg. |
| Time Frame | BL (pretransplant), 1, 3, 6, 9, 12 months posttransplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population, all randomized and transplanted participants. n = participants who had both baseline and postbaseline values. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept Less Intensive (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab ; Intravenous (IV), 20 mg, Day 1 and Day 5 Belatacept More Intensive (MI) ; Intravenous (IV), 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF), Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (Short term [ST]), ≤ 1 g/day, 4 years (Long-term extension [LTE]) | Belatacept More Intensive (MI): IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF , Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Drug: Belatacept Less Intensive (LI), IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (Short Term [ST]), in accordance with local practice and the package insert, 4 years (LTE) + MMF, IV/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE) |
| Measure Participants | 50 | 48 | 49 | 53 | 50 |
| BL (n=50, 48, 49, 53, 49) |
64.5
(12.86)
|
63.1
(11.50)
|
62.9
(10.54)
|
67.5
(12.55)
|
68.6
(12.07)
|
| 1 month (n=50, 48, 49, 52, 48) |
74.4
(10.34)
|
74.7
(9.51)
|
72.6
(13.84)
|
77.8
(10.26)
|
74.6
(10.76)
|
| Change from BL to 1 month (n=50, 48, 49, 52, 47) |
10.0
(14.53)
|
11.7
(12.48)
|
9.7
(16.27)
|
10.7
(13.80)
|
5.8
(14.05)
|
| 3 months (n=44, 46, 41, 48, 42) |
77.4
(9.57)
|
78.3
(10.85)
|
76.1
(10.81)
|
81.7
(10.94)
|
78.2
(9.86)
|
| Change from BL to 3 months (n=44, 46, 41, 48, 41) |
11.5
(14.32)
|
15.2
(11.90)
|
12.0
(15.70)
|
14.4
(15.27)
|
9.9
(15.35)
|
| 6 months (n=43, 40, 36, 47, 37) |
74.4
(10.63)
|
79.4
(10.17)
|
76.3
(9.69)
|
77.8
(12.68)
|
76.6
(9.11)
|
| Change from BL to 6 months (n=43, 40, 36, 47, 36) |
8.8
(15.49)
|
17.0
(12.86)
|
12.5
(14.93)
|
10.7
(14.44)
|
8.6
(14.58)
|
| 9 months (n=34, 30, 29, 41, 31) |
75.4
(9.96)
|
78.5
(11.45)
|
77.6
(9.10)
|
79.5
(10.74)
|
79.5
(10.15)
|
| Change from BL to 9 months (n=34, 30, 29, 41, 31) |
10.0
(14.41)
|
15.2
(16.91)
|
13.2
(14.54)
|
11.2
(15.37)
|
11.2
(13.25)
|
| 12 months (n=42, 37, 36, 46, 38) |
76.5
(9.38)
|
78.5
(11.43)
|
74.5
(8.54)
|
80.3
(10.21)
|
79.5
(11.24)
|
| Change from BL to 12 months (n=42, 37, 36, 46, 37) |
10.26
(15.71)
|
16.3
(15.28)
|
10.6
(14.35)
|
10.21
(13.6)
|
10.8
(13.20)
|
| Title | Summary Statistics for Mean Arterial Pressure: 12-month Treatment Phase |
|---|---|
| Description | |
| Time Frame | BL (pretransplant), 1, 3, 6, 9, 12 months posttransplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population, all randomized and transplanted participants. n = participants who had both baseline and postbaseline values. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept Less Intensive (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab ; Intravenous (IV), 20 mg, Day 1 and Day 5 Belatacept More Intensive (MI) ; Intravenous (IV), 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF), Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (Short term [ST]), ≤ 1 g/day, 4 years (Long-term extension [LTE]) | Belatacept More Intensive (MI): IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF , Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Drug: Belatacept Less Intensive (LI), IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (Short Term [ST]), in accordance with local practice and the package insert, 4 years (LTE) + MMF, IV/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE) |
| Measure Participants | 50 | 48 | 49 | 53 | 50 |
| BL (n=50, 48, 49, 53, 49) |
81.4
(12.98)
|
80.5
(13.58)
|
79.1
(10.32)
|
85.4
(12.97)
|
87.5
(13.42)
|
| 1 month (n=50, 48, 49, 52, 48) |
90.7
(10.97)
|
91.9
(10.44)
|
88.7
(14.09)
|
95.0
(9.89)
|
91.3
(11.61)
|
| Change from BL to 1 month (n=50, 48, 49, 52, 47) |
9.3
(14.58)
|
11.4
(14.96)
|
9.6
(16.75)
|
10.0
(13.86)
|
4.1
(15.76)
|
| 3 months (n=44, 46, 41, 48, 41) |
93.9
(9.78)
|
94.5
(11.14)
|
92.2
(12.18)
|
100.1
(12.29)
|
96.5
(9.01)
|
| Change from BL to 3 months (n=44, 46, 41, 48, 41) |
11.3
(15.40)
|
14.0
(14.21)
|
12.2
(15.95)
|
15.1
(17.11)
|
9.6
(15.59)
|
| 6 months (n=43, 40, 36, 47, 37) |
91.0
(10.70)
|
95.1
(10.92)
|
92.4
(9.94)
|
95.4
(15.04)
|
95.0
(11.70)
|
| Change from BL to 6 months (n=43, 40, 36, 47, 36) |
8.7
(15.71)
|
14.4
(15.63)
|
12.6
(14.35)
|
10.5
(17.18)
|
8.5
(16.74)
|
| 9 months (n=34, 30, 29, 41, 31) |
92.1
(10.41)
|
94.3
(10.22)
|
93.0
(8.68)
|
98.2
(12.46)
|
97.7
(10.34)
|
| Change from BL to 9 months (n=34, 30, 29, 41, 31) |
10.1
(15.06)
|
13.1
(19.90)
|
13.2
(13.82)
|
12.3
(17.71)
|
11.3
(13.25)
|
| 12 months (n=42, 37, 36, 46, 38) |
93.0
(8.61)
|
94.6
(11.90)
|
90.1
(8.89)
|
99.2
(11.56)
|
99.0
(12.13)
|
| Change from BL to 12 months (n=42, 37, 36, 46, 37) |
10.1
(15.41)
|
14.3
(18.11)
|
10.6
(13.06)
|
14.3
(17.12)
|
12.1
(15.76)
|
| Title | Percentage of Participants Who Developed Hypertension in 12-month Treatment Phase |
|---|---|
| Description | Percentage of participants who develop hypertension after randomization and transplantation. Transient post-operative increases in BP were not to be counted as new onset hypertension. Hypertension was to be assessed only at or after the Week 4 visit. Participants were considered to have hypertension when either of the following criteria were met: (1) SBP ≥ 130 mm Hg or DBP ≥ 80 mm Hg or (2) participant received an antihypertensive medication(s) for the indication of hypertension or due to medical history of hypertension. |
| Time Frame | 6 and 12 months posttransplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population, all randomized and transplanted participants. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept Less Intensive (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab ; Intravenous (IV), 20 mg, Day 1 and Day 5 Belatacept More Intensive (MI) ; Intravenous (IV), 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF), Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (Short term [ST]), ≤ 1 g/day, 4 years (Long-term extension [LTE]) | Belatacept More Intensive (MI): IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF , Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Drug: Belatacept Less Intensive (LI), IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (Short Term [ST]), in accordance with local practice and the package insert, 4 years (LTE) + MMF, IV/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE) |
| Measure Participants | 17 | 15 | 16 | 16 | 12 |
| By 6 months |
94.1
188.2%
|
93.3
194.4%
|
93.8
191.4%
|
100.0
188.7%
|
100
200%
|
| By 12 months |
100
200%
|
93.3
194.4%
|
93.8
191.4%
|
100.0
188.7%
|
100.0
200%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 6 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -5.9 | |
| Confidence Interval |
(2-Sided) 95% -21.2 to 6.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 6 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -6.7 | |
| Confidence Interval |
(2-Sided) 95% -18.2 to 5.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 6 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -6.3 | |
| Confidence Interval |
(2-Sided) 95% -14.9 to 4.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 6 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -5.9 | |
| Confidence Interval |
(2-Sided) 95% -25.1 to 7.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 6 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -6.7 | |
| Confidence Interval |
(2-Sided) 95% -15.6 to 4.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 6 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -6.3 | |
| Confidence Interval |
(2-Sided) 95% -12.7 to 3.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -6.7 | |
| Confidence Interval |
(2-Sided) 95% -18.2 to 5.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -6.3 | |
| Confidence Interval |
(2-Sided) 95% -14.9 to 4.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -6.7 | |
| Confidence Interval |
(2-Sided) 95% -15.6 to 4.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -6.3 | |
| Confidence Interval |
(2-Sided) 95% -12.7 to 3.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
| Title | Percentage of Participants Who Have Hypertension at Any Given Time During the 12-month Treatment Phase |
|---|---|
| Description | Percentage of participants at any given time who meet the definition of hypertension. Participants were considered to have hypertension when either of the following criteria were met: (1) SBP ≥ 130 mm Hg or DBP ≥ 80 mm Hg or (2) participant received an antihypertensive medication(s) for the indication of hypertension or due to medical history of hypertension. |
| Time Frame | 6 and 12 months posttransplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population, all randomized and transplanted participants. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept Less Intensive (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab ; Intravenous (IV), 20 mg, Day 1 and Day 5 Belatacept More Intensive (MI) ; Intravenous (IV), 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF), Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (Short term [ST]), ≤ 1 g/day, 4 years (Long-term extension [LTE]) | Belatacept More Intensive (MI): IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF , Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Drug: Belatacept Less Intensive (LI), IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (Short Term [ST]), in accordance with local practice and the package insert, 4 years (LTE) + MMF, IV/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE) |
| Measure Participants | 50 | 48 | 49 | 53 | 50 |
| By 6 months |
64.0
128%
|
77.1
160.6%
|
69.4
141.6%
|
71.7
135.3%
|
70.0
140%
|
| By 12 months |
72.0
144%
|
68.8
143.3%
|
59.2
120.8%
|
79.2
149.4%
|
70.0
140%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 6 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -7.7 | |
| Confidence Interval |
(2-Sided) 95% -25.6 to 10.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 6 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 5.4 | |
| Confidence Interval |
(2-Sided) 95% -11.7 to 22.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 6 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -2.3 | |
| Confidence Interval |
(2-Sided) 95% -20.1 to 15.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -6.0 | |
| Confidence Interval |
(2-Sided) 95% -24.0 to 12.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 6 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 7.1 | |
| Confidence Interval |
(2-Sided) 95% -10.5 to 24.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 6 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.6 | |
| Confidence Interval |
(2-Sided) 95% -18.5 to 17.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -7.2 | |
| Confidence Interval |
(2-Sided) 95% -23.3 to 9.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -10.5 | |
| Confidence Interval |
(2-Sided) 95% -27.4 to 6.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -20.1 | |
| Confidence Interval |
(2-Sided) 95% -37.5 to -2.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 2.0 | |
| Confidence Interval |
(2-Sided) 95% -15.5 to 19.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.3 | |
| Confidence Interval |
(2-Sided) 95% -19.4 to 16.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -10.8 | |
| Confidence Interval |
(2-Sided) 95% -29.3 to 7.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
| Title | Number of Participants Who Had Adverse Events (AEs), Death, Serious AEs (SAEs) or Were Discontinued Due to AEs (Includes Long Term Extension [LTE] Data) |
|---|---|
| Description | AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. |
| Time Frame | Day 1 (randomization) to Week 104 + within 56 Days after the last infusion/dose, Deaths were monitored up to database lock (20-June-2011) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT-LTE population, (all randomized and transplanted participants who entered long term extension). Participants were grouped according to the treatment to which they were randomized initially. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 30 | 27 | 24 | 38 | 26 |
| SAEs |
18
36%
|
22
45.8%
|
17
34.7%
|
29
54.7%
|
21
42%
|
| Related SAEs |
5
10%
|
9
18.8%
|
9
18.4%
|
12
22.6%
|
9
18%
|
| Discontinued due to SAEs |
2
4%
|
4
8.3%
|
1
2%
|
1
1.9%
|
0
0%
|
| AEs |
30
60%
|
27
56.3%
|
23
46.9%
|
38
71.7%
|
26
52%
|
| Related AEs |
27
54%
|
21
43.8%
|
20
40.8%
|
33
62.3%
|
23
46%
|
| Discontinued due to AEs |
2
4%
|
5
10.4%
|
1
2%
|
1
1.9%
|
0
0%
|
| Deaths (due to AE) |
2
4%
|
3
6.3%
|
1
2%
|
3
5.7%
|
0
0%
|
| Deaths (not due to AE) |
0
0%
|
1
2.1%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants Who Had AEs of Special Interest During the LTE |
|---|---|
| Description | AE of special interest included malignancies (including skin carcinomas), infections (viral, cytomegalovirus, herpes, fungal, and bacterial). |
| Time Frame | Day 1 (randomization) through database lock (20-June-2011) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT-LTE population, all randomized and transplanted participants who entered long term extension |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 30 | 27 | 24 | 38 | 26 |
| Malignancies |
1
2%
|
4
8.3%
|
3
6.1%
|
8
15.1%
|
3
6%
|
| Infections and Infestations |
8
16%
|
6
12.5%
|
9
18.4%
|
11
20.8%
|
8
16%
|
| Title | Number of Participants With Marked Hematology Abnormalities During the LTE |
|---|---|
| Description | Low platelet count: <50*10^9 c/µl; Low leukocytes: <2.0*10^3 c/µl; Low lymphocytes (absolute): <0.5*10^3 c/µl; Low neutrophils (absolute): <1.0*10^3 c/µl. |
| Time Frame | Every 4 weeks from Week 53 to Week 104. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT-LTE population: All randomized and transplanted participants who entered long-term extension. n= participants who had a laboratory test reading after transplant for the specific analyte. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 30 | 27 | 24 | 38 | 26 |
| Low Platelets: (n=29, 26, 22, 37, 25) |
1
2%
|
2
4.2%
|
0
0%
|
2
3.8%
|
0
0%
|
| Low Leukocytes : (n=29, 27, 22, 37, 25) |
1
2%
|
2
4.2%
|
0
0%
|
3
5.7%
|
0
0%
|
| Low Absolute Lymphocyte: (n=29, 27, 22, 36, 25) |
8
16%
|
3
6.3%
|
3
6.1%
|
5
9.4%
|
3
6%
|
| Low Absolute Neutrophils: (n=29, 27, 22, 36, 25) |
0
0%
|
2
4.2%
|
1
2%
|
2
3.8%
|
0
0%
|
| Title | Number of Participants With Marked Liver and Kidney Function Abnormalities During the LTE |
|---|---|
| Description | ULN= upper limit of normal; Normal ranges are provided by the Central Laboratory and may vary according to sex and age. High alanine aminotransferase (ALT): >5.0*ULN U/L; High aspartate aminotransferase (AST): >5.0*ULN U/L; High direct bilirubin: >3.0*ULN mg/dL; High g-glutamyl transferase (GGT): >5.0*ULN U/L; High total bilirubin: >3.0*ULN mg/dL; High creatinine: > 3.0*ULN mg/dL |
| Time Frame | Every 4 weeks from Week 53 to Week 104. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT-LTE population: All randomized and transplanted participants who entered long-term extension. n= participants who had a laboratory test reading after transplant for the specific analyte. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 29 | 27 | 22 | 37 | 25 |
| High ALT |
0
0%
|
2
4.2%
|
1
2%
|
4
7.5%
|
3
6%
|
| High AST |
0
0%
|
3
6.3%
|
2
4.1%
|
4
7.5%
|
3
6%
|
| High Direct Bilirubin |
1
2%
|
4
8.3%
|
1
2%
|
3
5.7%
|
2
4%
|
| High GGT |
2
4%
|
6
12.5%
|
6
12.2%
|
13
24.5%
|
8
16%
|
| High Total Bilirubin |
1
2%
|
3
6.3%
|
1
2%
|
2
3.8%
|
0
0%
|
| High Creatinine |
0
0%
|
0
0%
|
0
0%
|
1
1.9%
|
0
0%
|
| Title | Number of Participants With Marked Electrolytes, Protein and Metabolic Test Abnormalities During the LTE |
|---|---|
| Description | Low Serum Potassium: <3.0 meq/L; High serum potassium:>6.0 mEq/L; Low serum magnesium:<0.8 mEq/L; Low serum sodium: <130 mEq/L; High serum sodium: >155 mEq/L; Low inorganic phosphorus: <2.0 mg/dL; High uric acid: >10 mg/dL |
| Time Frame | Every 4 weeks from Week 53 to Week 104. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT-LTE population: All randomized and transplanted participants who entered long-term extension. n= participants who had a laboratory test reading after transplant for the specific analyte. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 29 | 27 | 22 | 37 | 25 |
| Low Serum Potassium |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| High Serum Potassium |
1
2%
|
1
2.1%
|
0
0%
|
0
0%
|
0
0%
|
| Low Serum Sodium |
1
2%
|
2
4.2%
|
1
2%
|
1
1.9%
|
0
0%
|
| High Serum Sodium |
0
0%
|
0
0%
|
1
2%
|
0
0%
|
0
0%
|
| Low Inorganic Phosphorus |
1
2%
|
0
0%
|
1
2%
|
1
1.9%
|
0
0%
|
| High Uric Acid |
0
0%
|
1
2.1%
|
0
0%
|
6
11.3%
|
6
12%
|
| Title | Number of Participants Who Received Anti-hypertensive Therapy at Month 12 |
|---|---|
| Description | |
| Time Frame | 12 months posttransplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population, all randomized and transplanted participants. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept Less Intensive (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab ; Intravenous (IV), 20 mg, Day 1 and Day 5 Belatacept More Intensive (MI) ; Intravenous (IV), 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF), Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (Short term [ST]), ≤ 1 g/day, 4 years (Long-term extension [LTE]) | Belatacept More Intensive (MI): IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF , Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Drug: Belatacept Less Intensive (LI), IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (Short Term [ST]), in accordance with local practice and the package insert, 4 years (LTE) + MMF, IV/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE) |
| Measure Participants | 41 | 39 | 36 | 48 | 42 |
| Received at least 1 medication |
20
40%
|
19
39.6%
|
14
28.6%
|
26
49.1%
|
21
42%
|
| Received 1 medication |
13
26%
|
16
33.3%
|
8
16.3%
|
17
32.1%
|
12
24%
|
| Received 2 medications |
6
12%
|
2
4.2%
|
2
4.1%
|
5
9.4%
|
5
10%
|
| Received 3 medications |
1
2%
|
1
2.1%
|
4
8.2%
|
3
5.7%
|
3
6%
|
| Received 4 medications |
1
2%
|
0
0%
|
0
0%
|
1
1.9%
|
1
2%
|
| Title | Percentage of Participants With New Onset Diabetes Mellitus (NODM): 12-month Treatment Phase |
|---|---|
| Description | A participant who did not have diabetes prior to randomization was determined to have NODM if(i) the participant received an antidiabetic medication for a duration of at least 30 days or(ii) at least two fasting plasma glucose (FPG) tests indicate that FPG is>=126 mg/dL (7.0 mmol/L). For 95% CI within each group, normal approximation is used if N>=5. For 95% CI of difference, adjustment is made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. |
| Time Frame | 6 and 12 months posttransplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population, all randomized participants without Diabetes Mellitus (pre-transplantation). |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 31 | 32 | 36 | 38 | 37 |
| 6 months |
35.5
71%
|
15.6
32.5%
|
13.9
28.4%
|
21.1
39.8%
|
35.1
70.2%
|
| 12 months |
35.5
71%
|
15.6
32.5%
|
13.9
28.4%
|
23.7
44.7%
|
37.8
75.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 6 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 14.4 | |
| Confidence Interval |
(2-Sided) 95% -6.3 to 36.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 6 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -5.4 | |
| Confidence Interval |
(2-Sided) 95% -23.4 to 10.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 6 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -7.2 | |
| Confidence Interval |
(2-Sided) 95% -23.4 to 10.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 6 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.3 | |
| Confidence Interval |
(2-Sided) 95% -22.0 to 23.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 6 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -19.5 | |
| Confidence Interval |
(2-Sided) 95% -38.6 to -0.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 6 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -21.2 | |
| Confidence Interval |
(2-Sided) 95% -39.1 to -1.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 11.8 | |
| Confidence Interval |
(2-Sided) 95% -8.7 to 34.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -8.1 | |
| Confidence Interval |
(2-Sided) 95% -25.2 to 8.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 4: Tacrolimus + MMF |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -9.8 | |
| Confidence Interval |
(2-Sided) 95% -26.3 to 7.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Basiliximab+Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 12. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -2.4 | |
| Confidence Interval |
(2-Sided) 95% -24.5 to 21.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Belatacept (MI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -22.2 | |
| Confidence Interval |
(2-Sided) 95% -40.5 to -1.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Belatacept (LI) + MMF, Group 5: Tacrolimus |
|---|---|---|
| Comments | Analysis at Month 12 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -23.9 | |
| Confidence Interval |
(2-Sided) 95% -41.8 to -4.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | For 95% CI of difference, adjustment was made for randomization strata (HCV-Infection status at baseline) if N >= 5 in each treatment arm. Otherwise exact method ignoring stratification was used. | |
| Title | Glycosylated Hemoglobin (HbA1C) Values: 12-month Treatment Phase |
|---|---|
| Description | The HbA1c test is important in diabetes as a long-term measure of control over blood glucose, where the glucose bound to hemoglobin during the past 3-4 months is measured. A baseline diabetes participant was one who had a medical history of diabetes or being under anti-diabetic medication at the time of the transplantation. BL = baseline, DM = Diabetes mellitus. |
| Time Frame | 6, 12 months (mth) posttransplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population, all randomized and transplanted participants. n = Participants with both baseline and postbaseline values. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept Less Intensive (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab ; Intravenous (IV), 20 mg, Day 1 and Day 5 Belatacept More Intensive (MI) ; Intravenous (IV), 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF), Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (Short term [ST]), ≤ 1 g/day, 4 years (Long-term extension [LTE]) | Belatacept More Intensive (MI): IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF , Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Drug: Belatacept Less Intensive (LI), IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (LTE) + MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (Short Term [ST]), in accordance with local practice and the package insert, 4 years (LTE) + MMF, IV/Capsules, IV/Oral, 1-2g/day, 52 weeks (ST), ≤ 1 g/day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE) |
| Measure Participants | 50 | 48 | 49 | 53 | 50 |
| 6 mo: All participants (n=39, 34, 38, 47, 35) |
5.8
(1.07)
|
5.8
(0.96)
|
5.6
(0.75)
|
5.4
(0.90)
|
5.4
(0.84)
|
| 6 mo: DM at BL (n=15, 12, 10, 12, 10) |
6.5
(1.19)
|
6.6
(1.02)
|
6.1
(0.76)
|
5.8
(1.19)
|
5.4
(0.59)
|
| 6 mo: DM at BL/DM at 6m (n=23, 14, 14, 19, 18) |
6.1
(1.17)
|
6.4
(1.02)
|
5.9
(0.90)
|
5.5
(1.04)
|
5.4
(0.62)
|
| 12 mo: All participants (n=40, 35, 35, 44, 37) |
6.0
(1.32)
|
5.8
(1.03)
|
5.7
(0.97)
|
5.5
(0.76)
|
5.8
(1.85)
|
| 12 mo: DM at BL (n=15, 11, 7, 11, 12) |
6.9
(1.60)
|
6.7
(1.40)
|
6.7
(1.49)
|
6.2
(0.96)
|
6.5
(3.05)
|
| 12 mo: DM at BL/DM at 12 mth (n=23,13 ,11,18,20) |
6.3
(1.58)
|
6.6
(1.29)
|
6.2
(1.40)
|
6.0
(0.84)
|
6.3
(2.39)
|
| Title | Number of Participants Who Had AEs, Death, SAEs or Were Discontinued Due to AEs: 12-month Treatment Phase |
|---|---|
| Description | AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant administered an investigational product and that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event |
| Time Frame | Day 1 (randomization) to 12 m + 8 week follow-up or ≤ 56 days after discontinuation of study medication |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population: all randomized and transplanted participants |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 50 | 48 | 49 | 53 | 50 |
| Death |
4
8%
|
4
8.3%
|
9
18.4%
|
1
1.9%
|
4
8%
|
| SAEs |
28
56%
|
29
60.4%
|
37
75.5%
|
40
75.5%
|
35
70%
|
| Related SAEs |
12
24%
|
11
22.9%
|
14
28.6%
|
16
30.2%
|
19
38%
|
| Discontinued due to SAEs |
7
14%
|
6
12.5%
|
11
22.4%
|
4
7.5%
|
13
26%
|
| AEs |
50
100%
|
48
100%
|
48
98%
|
53
100%
|
50
100%
|
| Related AEs |
45
90%
|
34
70.8%
|
33
67.3%
|
42
79.2%
|
42
84%
|
| Discontinued due to AEs |
7
14%
|
7
14.6%
|
12
24.5%
|
7
13.2%
|
18
36%
|
| Title | Number of Participants Who Had Adverse Events of Special Interest During 12-month Treatment Phase |
|---|---|
| Description | AE of of special interest included malignancies (including skin carcinomas), infections (viral, cytomegalovirus, herpes, fungal, and bacterial), serious infections |
| Time Frame | Day 1 (randomization) to 12 months or ≤ 56 days after discontinuation of study medication |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population, all randomized and transplanted participants. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 50 | 48 | 49 | 53 | 50 |
| Malignancies |
1
2%
|
0
0%
|
2
4.1%
|
2
3.8%
|
2
4%
|
| Post-transplant lymphoproliferative disorder |
0
0%
|
0
0%
|
1
2%
|
0
0%
|
0
0%
|
| All Infections |
32
64%
|
39
81.3%
|
30
61.2%
|
31
58.5%
|
29
58%
|
| Bacterial infections |
5
10%
|
11
22.9%
|
11
22.4%
|
6
11.3%
|
13
26%
|
| Fungal infections |
6
12%
|
9
18.8%
|
14
28.6%
|
6
11.3%
|
5
10%
|
| Viral infections |
10
20%
|
11
22.9%
|
14
28.6%
|
9
17%
|
7
14%
|
| Cytomegalovirus infections |
5
10%
|
4
8.3%
|
10
20.4%
|
4
7.5%
|
1
2%
|
| Polyoma virus infections |
0
0%
|
1
2.1%
|
0
0%
|
0
0%
|
0
0%
|
| Herpes infections |
3
6%
|
3
6.3%
|
4
8.2%
|
3
5.7%
|
2
4%
|
| Hepatitis C virus recurrence |
14
28%
|
7
14.6%
|
6
12.2%
|
13
24.5%
|
9
18%
|
| Serious infections |
11
22%
|
12
25%
|
13
26.5%
|
12
22.6%
|
12
24%
|
| Autoimmune events |
0
0%
|
0
0%
|
1
2%
|
0
0%
|
2
4%
|
| Acute peri-infusional events |
5
10%
|
1
2.1%
|
0
0%
|
NA
NaN
|
NA
NaN
|
| Thrombotic and embolic events |
3
6%
|
3
6.3%
|
7
14.3%
|
10
18.9%
|
5
10%
|
| Title | Number of Participants With Marked Hematology Abnormalities: 12-month Treatment Phase |
|---|---|
| Description | Low hemoglobin: <8 g/dL; Low platelet count: <50*10^9 C/L; Low leukocytes: <2.0 *10^3 c/µL; Low lymphocytes (absolute): <0.5*10^3 c/µL; Low neutrophils (absolute): <1.0*10^3 Cc/µL. |
| Time Frame | Baseline (pretransplant), 2, 4, 8, 12 weeks, and every 4 weeks for week 16 to 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population, all randomized and transplanted participants. n= participants with all observations. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 50 | 48 | 49 | 53 | 50 |
| Low Hemoglobin: (n=48, 46, 44, 52, 50) |
2
4%
|
6
12.5%
|
2
4.1%
|
0
0%
|
6
12%
|
| Low Platelets: (n=48, 46, 43, 52, 50) |
0
0%
|
1
2.1%
|
4
8.2%
|
2
3.8%
|
2
4%
|
| Low Leukocytes : (n=48, 46, 44, 52, 50) |
6
12%
|
6
12.5%
|
5
10.2%
|
4
7.5%
|
3
6%
|
| Low Absolute Lymphocyte: (n=48, 46, 44, 52, 50) |
29
58%
|
18
37.5%
|
26
53.1%
|
17
32.1%
|
16
32%
|
| Low Absolute Neutrophils : (n=48, 46, 44, 52, 50) |
6
12%
|
4
8.3%
|
4
8.2%
|
8
15.1%
|
1
2%
|
| Title | Number of Participants With Marked Liver and Kidney Function Abnormalities: 12-month Treatment Phase |
|---|---|
| Description | ULN= upper limit of normal; Normal ranges are provided by the central laboratory and may vary according to sex and age. High alkaline phosphatase (ALP): >5.0*ULN U/L; High alanine aminotransferase (ALT): >5.0*ULN U/L; High aspartate aminotransferase (AST): >5.0*ULN U/L; High direct bilirubin: >3.0 * ULN mg/dL; High g-glutamyl transferase (GGT): >5.0*ULN U/L; High total bilirubin: >3.0*ULN mg/dL; High creatinine: > 3.0*ULN mg/dL |
| Time Frame | Baseline (pretransplant), 4, 12, 24, 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population, all randomized and transplanted participants. n= participants with all observations. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 50 | 48 | 49 | 53 | 50 |
| High ALP: (n=48, 47, 44, 53, 50) |
5
10%
|
6
12.5%
|
6
12.2%
|
4
7.5%
|
6
12%
|
| High ALT: (n=48, 47, 44, 53, 50) |
16
32%
|
18
37.5%
|
19
38.8%
|
16
30.2%
|
9
18%
|
| High AST: (n=48, 47, 44, 53, 50) |
9
18%
|
14
29.2%
|
16
32.7%
|
8
15.1%
|
2
4%
|
| High Direct Bilirubin: (n=48, 47, 44, 53, 50) |
15
30%
|
18
37.5%
|
19
38.8%
|
20
37.7%
|
16
32%
|
| High GGT: (n=48, 47, 44, 53, 50) |
25
50%
|
24
50%
|
24
49%
|
27
50.9%
|
22
44%
|
| High Total Bilirubin: (n=48, 47, 44, 53, 50) |
9
18%
|
13
27.1%
|
16
32.7%
|
12
22.6%
|
10
20%
|
| High Creatinine: (n=47, 44, 44, 53, 50) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Marked Electrolytes, Protein and Metabolic Test Abnormalities: 12-month Treatment Phase |
|---|---|
| Description | Low total calcium: <7 mg/dL; High total calcium: >12.5 mg/dL ; Low bicarbonate: <11 mEq/L; Low serum potassium: <3.0 mEq/L; High serum potassium:>6.0 mEq/L; High serum magnesium: >2.46 mEq/L; Low serum magnesium:<0.8 mEq/L; Low serum sodium: <130 mEq/L; High serum sodium: >155 mEq/L; Low inorganic phosphorus: <2.0 mg/dL; Low albumin: <2 g/dL; High uric acid: >10 mg/dL |
| Time Frame | Baseline (pretransplant), Weeks 4, 12, 24, and 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population, all randomized and transplanted participants. n= participants with all observations. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 50 | 48 | 49 | 53 | 50 |
| Low Total Calcium (n=48, 47, 44, 53, 50) |
0
0%
|
1
2.1%
|
1
2%
|
1
1.9%
|
0
0%
|
| High Total Calcium (n=48, 47, 44, 53, 50) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Low Bicarbonate (n=47, 47, 44, 53, 50) |
0
0%
|
0
0%
|
0
0%
|
1
1.9%
|
0
0%
|
| Low Serum Potassium (n=48, 47, 44, 53, 50) |
0
0%
|
2
4.2%
|
1
2%
|
1
1.9%
|
0
0%
|
| High Serum Potassium (n=48, 47, 44, 53, 50) |
1
2%
|
0
0%
|
1
2%
|
2
3.8%
|
1
2%
|
| High Serum Magnesium (n=48, 47, 44, 53, 50) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Low Serum Magnesium (n=48, 47, 44, 53, 50) |
2
4%
|
0
0%
|
2
4.1%
|
0
0%
|
1
2%
|
| Low Serum Sodium (n=48, 47, 44, 53, 50) |
3
6%
|
2
4.2%
|
2
4.1%
|
2
3.8%
|
2
4%
|
| High Serum Sodium (n=48, 47, 44, 53, 50) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Low Inorganic Phosphorus (n=48, 47, 44, 53, 50) |
0
0%
|
2
4.2%
|
1
2%
|
2
3.8%
|
0
0%
|
| Low Albumin (n=47, 47, 45, 53, 50) |
2
4%
|
1
2.1%
|
0
0%
|
0
0%
|
0
0%
|
| High Uric Acid (n=48, 47, 44, 53, 50) |
2
4%
|
1
2.1%
|
2
4.1%
|
5
9.4%
|
5
10%
|
| Title | Number of Participants Who Had Abnormalities in Electrocardiograms: 12-month Treatment Phase |
|---|---|
| Description | |
| Time Frame | Baseline (pretransplant), Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ECG data was not analyzed. |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 0 | 0 | 0 | 0 | 0 |
| Title | Change in Protein to Creatinine Ratio From Month 3 to Month 12. |
|---|---|
| Description | |
| Time Frame | Month 3 and 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Protein creatinine ratio change was not analyzed |
| Arm/Group Title | Group 1: Basiliximab+Belatacept (MI) + MMF | Group 2: Belatacept (MI) + MMF | Group 3: Belatacept (LI) + MMF | Group 4: Tacrolimus + MMF | Group 5: Tacrolimus |
|---|---|---|---|---|---|
| Arm/Group Description | Basiliximab- Intravenous (IV), 20 mg, on Day 1 and Day 5; Belatacept More Intensive (MI)-IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20 and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), and 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Mycophenolate Mofetil (MMF)-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept MI- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST), and 5 mg/kg, every 4 weeks, 4 years (LTE); MMF-IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Belatacept Less Intensive (LI)- IV, 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (ST]), 5 mg/kg, every 4 weeks, 4 years (LTE); MMF, Intravenous (IV)/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, 4 years (LTE); MMF, IV/Capsules, IV/Oral, 1-2g/Day, 52 weeks (ST), and ≤ 1 g/Day, 4 years (LTE) | Tacrolimus, Capsules, Oral, 6-12 ng/mL trough level, twice daily, 52 weeks (ST), in accordance with local practice and the package insert, and 4 years (LTE) |
| Measure Participants | 0 | 0 | 0 | 0 | 0 |
Adverse Events
| Time Frame | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||
| Arm/Group Title | Basiliximab+Belatacept (MI)+Mycophenolate Mofetil (MMF) | MI+MMF | Belaticept (LI) + MMF | Tacrolimus | Tacrolimus + MMF | |||||
| Arm/Group Description | ||||||||||
All Cause Mortality |
||||||||||
| Basiliximab+Belatacept (MI)+Mycophenolate Mofetil (MMF) | MI+MMF | Belaticept (LI) + MMF | Tacrolimus | Tacrolimus + MMF | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | |||||
Serious Adverse Events |
||||||||||
| Basiliximab+Belatacept (MI)+Mycophenolate Mofetil (MMF) | MI+MMF | Belaticept (LI) + MMF | Tacrolimus | Tacrolimus + MMF | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 18/30 (60%) | 17/24 (70.8%) | 22/27 (81.5%) | 21/26 (80.8%) | 29/38 (76.3%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 0/30 (0%) | 1/24 (4.2%) | 2/27 (7.4%) | 2/26 (7.7%) | 2/38 (5.3%) | |||||
| Normochromic normocytic anaemia | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Pancytopenia | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Leukopenia | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Lymphopenia | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Coagulopathy | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Febrile neutropenia | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Cardiac disorders | ||||||||||
| Atrial fibrillation | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Pericardial effusion | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Pericarditis | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Angina pectoris | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Coronary artery occlusion | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Cardiac arrest | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Coronary artery disease | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Tachycardia | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Eye disorders | ||||||||||
| Retinal vein occlusion | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Visual impairment | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Retinal detachment | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Ascites | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 2/26 (7.7%) | 0/38 (0%) | |||||
| Coeliac artery stenosis | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Gastric haemorrhage | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Nausea | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Rectal haemorrhage | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Abdominal hernia | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Localised intraabdominal fluid collection | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Volvulus | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Abdominal pain | 1/30 (3.3%) | 1/24 (4.2%) | 1/27 (3.7%) | 3/26 (11.5%) | 0/38 (0%) | |||||
| Oesophagitis | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Abdominal discomfort | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Diarrhoea | 0/30 (0%) | 0/24 (0%) | 2/27 (7.4%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Intestinal obstruction | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Gastritis | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Gastritis erosive | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Gastrointestinal haemorrhage | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 1/38 (2.6%) | |||||
| Pancreatitis | 3/30 (10%) | 2/24 (8.3%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Peritoneal haemorrhage | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Ileus | 1/30 (3.3%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Inguinal hernia | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Salivary gland fistula | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Stomatitis | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Vomiting | 1/30 (3.3%) | 1/24 (4.2%) | 1/27 (3.7%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| General disorders | ||||||||||
| General physical health deterioration | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Device leakage | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Medical device complication | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Hernia | 1/30 (3.3%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Chest pain | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 1/38 (2.6%) | |||||
| Influenza like illness | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Oedema peripheral | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Multi-organ failure | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Pyrexia | 2/30 (6.7%) | 2/24 (8.3%) | 1/27 (3.7%) | 1/26 (3.8%) | 1/38 (2.6%) | |||||
| Hepatobiliary disorders | ||||||||||
| Hepatic cirrhosis | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Biliary ischaemia | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Biloma | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Bile duct obstruction | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Hepatic artery thrombosis | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Bile duct stenosis | 3/30 (10%) | 3/24 (12.5%) | 0/27 (0%) | 2/26 (7.7%) | 2/38 (5.3%) | |||||
| Cholangitis | 2/30 (6.7%) | 2/24 (8.3%) | 1/27 (3.7%) | 2/26 (7.7%) | 5/38 (13.2%) | |||||
| Haemobilia | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Hepatic function abnormal | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Cholestasis | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Hepatic artery stenosis | 1/30 (3.3%) | 0/24 (0%) | 1/27 (3.7%) | 2/26 (7.7%) | 1/38 (2.6%) | |||||
| Hepatic failure | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Hepatic haemorrhage | 0/30 (0%) | 2/24 (8.3%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Acute hepatic failure | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Biliary tract disorder | 1/30 (3.3%) | 0/24 (0%) | 1/27 (3.7%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Portal vein stenosis | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Immune system disorders | ||||||||||
| Transplant rejection | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Infections and infestations | ||||||||||
| Liver abscess | 1/30 (3.3%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Oesophageal candidiasis | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Pneumonia | 1/30 (3.3%) | 1/24 (4.2%) | 0/27 (0%) | 5/26 (19.2%) | 0/38 (0%) | |||||
| Bronchitis | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Epstein-Barr virus infection | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Parvovirus infection | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Pyelonephritis | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 1/38 (2.6%) | |||||
| Sepsis | 1/30 (3.3%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Tracheobronchitis | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Abdominal abscess | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Bacteraemia | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Biliary abscess | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Abscess limb | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Cytomegalovirus infection | 1/30 (3.3%) | 1/24 (4.2%) | 2/27 (7.4%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Herpes zoster | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Influenza | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Hepatitis B | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Hepatitis C | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Bacterial infection | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Cellulitis | 0/30 (0%) | 0/24 (0%) | 2/27 (7.4%) | 1/26 (3.8%) | 1/38 (2.6%) | |||||
| Cytomegalovirus viraemia | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Incision site cellulitis | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Meningitis aseptic | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Upper respiratory tract infection | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Urinary tract infection | 1/30 (3.3%) | 2/24 (8.3%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Varicella | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Device related infection | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Groin abscess | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Pulmonary sepsis | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Wound infection | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 1/38 (2.6%) | |||||
| Cystitis | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Escherichia sepsis | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Gastrointestinal infection | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Hepatitis E | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Urosepsis | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Acetabulum fracture | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Femur fracture | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 2/38 (5.3%) | |||||
| Overdose | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Post-traumatic pain | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Incisional hernia | 2/30 (6.7%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 3/38 (7.9%) | |||||
| Fractured sacrum | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Spinal compression fracture | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Wound dehiscence | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 2/26 (7.7%) | 1/38 (2.6%) | |||||
| Ankle fracture | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Post procedural haemorrhage | 1/30 (3.3%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Fall | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Post procedural complication | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Biliary anastomosis complication | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Hepatic haematoma | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Vascular pseudoaneurysm | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Drug dispensing error | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Pelvic fracture | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Spinal fracture | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Upper limb fracture | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Investigations | ||||||||||
| Blood glucose increased | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Haematocrit decreased | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Liver function test abnormal | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 2/26 (7.7%) | 4/38 (10.5%) | |||||
| Blood bilirubin increased | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 1/26 (3.8%) | 1/38 (2.6%) | |||||
| Transaminases increased | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Body temperature increased | 1/30 (3.3%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Hepatic enzyme increased | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Obesity | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Hyponatraemia | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Hyperkalaemia | 2/30 (6.7%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Hypovolaemia | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Diabetes mellitus | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Dehydration | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Hyperglycaemia | 1/30 (3.3%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Hypoglycaemia | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Hypokalaemia | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Chondrocalcinosis pyrophosphate | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Intervertebral disc protrusion | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Back pain | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Flank pain | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Osteoarthritis | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Basal cell carcinoma | 0/30 (0%) | 0/24 (0%) | 2/27 (7.4%) | 1/26 (3.8%) | 1/38 (2.6%) | |||||
| Oesophageal cancer metastatic | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Endometrial cancer | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Transitional cell carcinoma | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Hepatic neoplasm malignant | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Squamous cell carcinoma of skin | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Hepatic neoplasm malignant recurrent | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Pleura carcinoma | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Bowen's disease | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Hepatic cancer metastatic | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Epstein-Barr virus associated lymphoproliferative disorder | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Lung neoplasm | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Tonsil cancer | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Nervous system disorders | ||||||||||
| Status epilepticus | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Tremor | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Encephalomalacia | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Encephalopathy | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Headache | 1/30 (3.3%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Grand mal convulsion | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Transient ischaemic attack | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Convulsion | 1/30 (3.3%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Hepatic encephalopathy | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Psychiatric disorders | ||||||||||
| Mental status changes | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 1/26 (3.8%) | 2/38 (5.3%) | |||||
| Alcoholism | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Suicidal ideation | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Agitation | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Mental disorder | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Suicide attempt | 0/30 (0%) | 1/24 (4.2%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Confusional state | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Transient psychosis | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Depression | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Renal and urinary disorders | ||||||||||
| Dysuria | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Renal failure acute | 1/30 (3.3%) | 1/24 (4.2%) | 2/27 (7.4%) | 4/26 (15.4%) | 3/38 (7.9%) | |||||
| Nephropathy toxic | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Renal failure | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Reproductive system and breast disorders | ||||||||||
| Epididymitis | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Gynaecomastia | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Acute respiratory distress syndrome | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Pulmonary hypertension | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Pulmonary embolism | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 2/38 (5.3%) | |||||
| Dyspnoea | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 1/26 (3.8%) | 1/38 (2.6%) | |||||
| Pulmonary oedema | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Acute respiratory failure | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Hepatopulmonary syndrome | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Pleural effusion | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 1/26 (3.8%) | 1/38 (2.6%) | |||||
| Lung disorder | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Skin ulcer | 1/30 (3.3%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Vascular disorders | ||||||||||
| Intra-abdominal haemorrhage | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Arterial thrombosis | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Artery dissection | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Arterial insufficiency | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Haemorrhage | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Hypotension | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Shock haemorrhagic | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Deep vein thrombosis | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 2/38 (5.3%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| Basiliximab+Belatacept (MI)+Mycophenolate Mofetil (MMF) | MI+MMF | Belaticept (LI) + MMF | Tacrolimus | Tacrolimus + MMF | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 29/30 (96.7%) | 23/24 (95.8%) | 27/27 (100%) | 25/26 (96.2%) | 38/38 (100%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 13/30 (43.3%) | 5/24 (20.8%) | 11/27 (40.7%) | 11/26 (42.3%) | 14/38 (36.8%) | |||||
| Iron deficiency anaemia | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Leukocytosis | 1/30 (3.3%) | 0/24 (0%) | 2/27 (7.4%) | 3/26 (11.5%) | 2/38 (5.3%) | |||||
| Leukopenia | 8/30 (26.7%) | 9/24 (37.5%) | 5/27 (18.5%) | 3/26 (11.5%) | 13/38 (34.2%) | |||||
| Coagulopathy | 1/30 (3.3%) | 1/24 (4.2%) | 2/27 (7.4%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Neutropenia | 3/30 (10%) | 4/24 (16.7%) | 3/27 (11.1%) | 1/26 (3.8%) | 3/38 (7.9%) | |||||
| Thrombocytopenia | 7/30 (23.3%) | 6/24 (25%) | 3/27 (11.1%) | 1/26 (3.8%) | 6/38 (15.8%) | |||||
| Cardiac disorders | ||||||||||
| Atrial fibrillation | 2/30 (6.7%) | 1/24 (4.2%) | 2/27 (7.4%) | 0/26 (0%) | 0/38 (0%) | |||||
| Bradycardia | 0/30 (0%) | 1/24 (4.2%) | 2/27 (7.4%) | 5/26 (19.2%) | 2/38 (5.3%) | |||||
| Pericardial effusion | 0/30 (0%) | 1/24 (4.2%) | 1/27 (3.7%) | 2/26 (7.7%) | 0/38 (0%) | |||||
| Tachycardia | 4/30 (13.3%) | 0/24 (0%) | 4/27 (14.8%) | 2/26 (7.7%) | 6/38 (15.8%) | |||||
| Ear and labyrinth disorders | ||||||||||
| Tinnitus | 0/30 (0%) | 1/24 (4.2%) | 1/27 (3.7%) | 1/26 (3.8%) | 2/38 (5.3%) | |||||
| Vertigo | 2/30 (6.7%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 3/38 (7.9%) | |||||
| Ear pain | 0/30 (0%) | 0/24 (0%) | 2/27 (7.4%) | 0/26 (0%) | 0/38 (0%) | |||||
| Eye disorders | ||||||||||
| Conjunctivitis | 0/30 (0%) | 0/24 (0%) | 2/27 (7.4%) | 0/26 (0%) | 0/38 (0%) | |||||
| Visual acuity reduced | 3/30 (10%) | 1/24 (4.2%) | 1/27 (3.7%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Cataract | 2/30 (6.7%) | 1/24 (4.2%) | 0/27 (0%) | 1/26 (3.8%) | 2/38 (5.3%) | |||||
| Eye pruritus | 0/30 (0%) | 0/24 (0%) | 2/27 (7.4%) | 0/26 (0%) | 0/38 (0%) | |||||
| Vision blurred | 3/30 (10%) | 0/24 (0%) | 2/27 (7.4%) | 1/26 (3.8%) | 1/38 (2.6%) | |||||
| Visual impairment | 2/30 (6.7%) | 0/24 (0%) | 2/27 (7.4%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Ocular hyperaemia | 0/30 (0%) | 0/24 (0%) | 2/27 (7.4%) | 0/26 (0%) | 0/38 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Ascites | 9/30 (30%) | 4/24 (16.7%) | 6/27 (22.2%) | 5/26 (19.2%) | 9/38 (23.7%) | |||||
| Nausea | 8/30 (26.7%) | 7/24 (29.2%) | 8/27 (29.6%) | 9/26 (34.6%) | 13/38 (34.2%) | |||||
| Proctalgia | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Rectal haemorrhage | 1/30 (3.3%) | 1/24 (4.2%) | 1/27 (3.7%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Abdominal pain lower | 0/30 (0%) | 0/24 (0%) | 2/27 (7.4%) | 2/26 (7.7%) | 1/38 (2.6%) | |||||
| Constipation | 12/30 (40%) | 7/24 (29.2%) | 10/27 (37%) | 10/26 (38.5%) | 14/38 (36.8%) | |||||
| Haemorrhoids | 1/30 (3.3%) | 0/24 (0%) | 2/27 (7.4%) | 1/26 (3.8%) | 3/38 (7.9%) | |||||
| Abdominal hernia | 2/30 (6.7%) | 0/24 (0%) | 2/27 (7.4%) | 0/26 (0%) | 3/38 (7.9%) | |||||
| Dyspepsia | 2/30 (6.7%) | 1/24 (4.2%) | 3/27 (11.1%) | 3/26 (11.5%) | 3/38 (7.9%) | |||||
| Localised intraabdominal fluid collection | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Mouth ulceration | 0/30 (0%) | 0/24 (0%) | 3/27 (11.1%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Abdominal pain | 10/30 (33.3%) | 3/24 (12.5%) | 8/27 (29.6%) | 9/26 (34.6%) | 13/38 (34.2%) | |||||
| Gastrooesophageal reflux disease | 2/30 (6.7%) | 0/24 (0%) | 1/27 (3.7%) | 1/26 (3.8%) | 2/38 (5.3%) | |||||
| Toothache | 2/30 (6.7%) | 1/24 (4.2%) | 1/27 (3.7%) | 2/26 (7.7%) | 1/38 (2.6%) | |||||
| Abdominal discomfort | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 3/26 (11.5%) | 1/38 (2.6%) | |||||
| Abdominal tenderness | 1/30 (3.3%) | 0/24 (0%) | 1/27 (3.7%) | 1/26 (3.8%) | 3/38 (7.9%) | |||||
| Diarrhoea | 12/30 (40%) | 10/24 (41.7%) | 10/27 (37%) | 11/26 (42.3%) | 23/38 (60.5%) | |||||
| Flatulence | 4/30 (13.3%) | 2/24 (8.3%) | 1/27 (3.7%) | 2/26 (7.7%) | 2/38 (5.3%) | |||||
| Varices oesophageal | 0/30 (0%) | 2/24 (8.3%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Abdominal pain upper | 3/30 (10%) | 3/24 (12.5%) | 3/27 (11.1%) | 4/26 (15.4%) | 4/38 (10.5%) | |||||
| Gastritis | 2/30 (6.7%) | 1/24 (4.2%) | 0/27 (0%) | 1/26 (3.8%) | 2/38 (5.3%) | |||||
| Periodontitis | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Abdominal distension | 7/30 (23.3%) | 3/24 (12.5%) | 3/27 (11.1%) | 2/26 (7.7%) | 5/38 (13.2%) | |||||
| Small intestinal obstruction | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 2/26 (7.7%) | 0/38 (0%) | |||||
| Ileus | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 2/38 (5.3%) | |||||
| Vomiting | 6/30 (20%) | 4/24 (16.7%) | 4/27 (14.8%) | 8/26 (30.8%) | 10/38 (26.3%) | |||||
| General disorders | ||||||||||
| Bloody discharge | 2/30 (6.7%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Fatigue | 11/30 (36.7%) | 2/24 (8.3%) | 4/27 (14.8%) | 12/26 (46.2%) | 12/38 (31.6%) | |||||
| Gait disturbance | 1/30 (3.3%) | 2/24 (8.3%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Oedema | 2/30 (6.7%) | 5/24 (20.8%) | 3/27 (11.1%) | 0/26 (0%) | 3/38 (7.9%) | |||||
| Irritability | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 3/26 (11.5%) | 2/38 (5.3%) | |||||
| Catheter site pain | 0/30 (0%) | 1/24 (4.2%) | 2/27 (7.4%) | 0/26 (0%) | 0/38 (0%) | |||||
| Chest pain | 2/30 (6.7%) | 4/24 (16.7%) | 4/27 (14.8%) | 2/26 (7.7%) | 1/38 (2.6%) | |||||
| Chills | 3/30 (10%) | 0/24 (0%) | 3/27 (11.1%) | 1/26 (3.8%) | 3/38 (7.9%) | |||||
| Generalised oedema | 1/30 (3.3%) | 1/24 (4.2%) | 3/27 (11.1%) | 3/26 (11.5%) | 2/38 (5.3%) | |||||
| Impaired healing | 1/30 (3.3%) | 1/24 (4.2%) | 2/27 (7.4%) | 2/26 (7.7%) | 0/38 (0%) | |||||
| Asthenia | 4/30 (13.3%) | 3/24 (12.5%) | 4/27 (14.8%) | 3/26 (11.5%) | 2/38 (5.3%) | |||||
| Influenza like illness | 1/30 (3.3%) | 1/24 (4.2%) | 1/27 (3.7%) | 3/26 (11.5%) | 2/38 (5.3%) | |||||
| Oedema peripheral | 11/30 (36.7%) | 7/24 (29.2%) | 10/27 (37%) | 10/26 (38.5%) | 19/38 (50%) | |||||
| Pain | 4/30 (13.3%) | 2/24 (8.3%) | 1/27 (3.7%) | 1/26 (3.8%) | 4/38 (10.5%) | |||||
| Malaise | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 2/26 (7.7%) | 4/38 (10.5%) | |||||
| Pyrexia | 11/30 (36.7%) | 8/24 (33.3%) | 10/27 (37%) | 8/26 (30.8%) | 9/38 (23.7%) | |||||
| Hepatobiliary disorders | ||||||||||
| Hyperbilirubinaemia | 1/30 (3.3%) | 2/24 (8.3%) | 1/27 (3.7%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Bile duct stenosis | 3/30 (10%) | 0/24 (0%) | 2/27 (7.4%) | 4/26 (15.4%) | 1/38 (2.6%) | |||||
| Cholangitis | 1/30 (3.3%) | 1/24 (4.2%) | 1/27 (3.7%) | 0/26 (0%) | 4/38 (10.5%) | |||||
| Cholestasis | 2/30 (6.7%) | 0/24 (0%) | 2/27 (7.4%) | 3/26 (11.5%) | 6/38 (15.8%) | |||||
| Hepatic artery stenosis | 1/30 (3.3%) | 1/24 (4.2%) | 2/27 (7.4%) | 1/26 (3.8%) | 1/38 (2.6%) | |||||
| Hepatic steatosis | 0/30 (0%) | 1/24 (4.2%) | 1/27 (3.7%) | 1/26 (3.8%) | 2/38 (5.3%) | |||||
| Jaundice | 0/30 (0%) | 2/24 (8.3%) | 1/27 (3.7%) | 2/26 (7.7%) | 2/38 (5.3%) | |||||
| Portal vein thrombosis | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 2/26 (7.7%) | 0/38 (0%) | |||||
| Immune system disorders | ||||||||||
| Seasonal allergy | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 2/26 (7.7%) | 0/38 (0%) | |||||
| Infections and infestations | ||||||||||
| Fungal skin infection | 2/30 (6.7%) | 1/24 (4.2%) | 3/27 (11.1%) | 0/26 (0%) | 0/38 (0%) | |||||
| Gastroenteritis | 0/30 (0%) | 2/24 (8.3%) | 2/27 (7.4%) | 0/26 (0%) | 0/38 (0%) | |||||
| Nasopharyngitis | 6/30 (20%) | 3/24 (12.5%) | 9/27 (33.3%) | 2/26 (7.7%) | 10/38 (26.3%) | |||||
| Pneumonia | 2/30 (6.7%) | 0/24 (0%) | 1/27 (3.7%) | 3/26 (11.5%) | 1/38 (2.6%) | |||||
| Bronchitis | 0/30 (0%) | 2/24 (8.3%) | 1/27 (3.7%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Oral herpes | 2/30 (6.7%) | 1/24 (4.2%) | 2/27 (7.4%) | 0/26 (0%) | 3/38 (7.9%) | |||||
| Bacteraemia | 2/30 (6.7%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 2/38 (5.3%) | |||||
| Clostridial infection | 0/30 (0%) | 0/24 (0%) | 2/27 (7.4%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Enterococcal infection | 0/30 (0%) | 0/24 (0%) | 3/27 (11.1%) | 0/26 (0%) | 3/38 (7.9%) | |||||
| Candidiasis | 0/30 (0%) | 0/24 (0%) | 2/27 (7.4%) | 0/26 (0%) | 0/38 (0%) | |||||
| Cytomegalovirus infection | 2/30 (6.7%) | 3/24 (12.5%) | 2/27 (7.4%) | 0/26 (0%) | 3/38 (7.9%) | |||||
| Herpes zoster | 0/30 (0%) | 3/24 (12.5%) | 2/27 (7.4%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Influenza | 1/30 (3.3%) | 0/24 (0%) | 2/27 (7.4%) | 1/26 (3.8%) | 1/38 (2.6%) | |||||
| Hepatitis C | 2/30 (6.7%) | 2/24 (8.3%) | 0/27 (0%) | 1/26 (3.8%) | 2/38 (5.3%) | |||||
| Laryngitis | 2/30 (6.7%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Respiratory tract infection | 2/30 (6.7%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Sinusitis | 1/30 (3.3%) | 1/24 (4.2%) | 2/27 (7.4%) | 1/26 (3.8%) | 3/38 (7.9%) | |||||
| Cellulitis | 1/30 (3.3%) | 1/24 (4.2%) | 2/27 (7.4%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Ear infection | 0/30 (0%) | 2/24 (8.3%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Staphylococcal infection | 0/30 (0%) | 0/24 (0%) | 3/27 (11.1%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Upper respiratory tract infection | 5/30 (16.7%) | 2/24 (8.3%) | 4/27 (14.8%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Urinary tract infection | 7/30 (23.3%) | 4/24 (16.7%) | 8/27 (29.6%) | 2/26 (7.7%) | 5/38 (13.2%) | |||||
| Device related infection | 1/30 (3.3%) | 0/24 (0%) | 1/27 (3.7%) | 3/26 (11.5%) | 0/38 (0%) | |||||
| Oral candidiasis | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 2/26 (7.7%) | 2/38 (5.3%) | |||||
| Pharyngitis | 0/30 (0%) | 2/24 (8.3%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Wound infection | 4/30 (13.3%) | 1/24 (4.2%) | 3/27 (11.1%) | 2/26 (7.7%) | 0/38 (0%) | |||||
| Cystitis | 0/30 (0%) | 2/24 (8.3%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Peritonitis bacterial | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 2/38 (5.3%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Incision site erythema | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Incisional hernia | 4/30 (13.3%) | 2/24 (8.3%) | 2/27 (7.4%) | 1/26 (3.8%) | 4/38 (10.5%) | |||||
| Procedural pain | 10/30 (33.3%) | 5/24 (20.8%) | 9/27 (33.3%) | 9/26 (34.6%) | 12/38 (31.6%) | |||||
| Rib fracture | 0/30 (0%) | 2/24 (8.3%) | 0/27 (0%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Spinal compression fracture | 0/30 (0%) | 0/24 (0%) | 2/27 (7.4%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Contusion | 0/30 (0%) | 3/24 (12.5%) | 2/27 (7.4%) | 0/26 (0%) | 5/38 (13.2%) | |||||
| Incision site complication | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Wound dehiscence | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 4/38 (10.5%) | |||||
| Excoriation | 1/30 (3.3%) | 1/24 (4.2%) | 3/27 (11.1%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Post procedural haemorrhage | 0/30 (0%) | 2/24 (8.3%) | 2/27 (7.4%) | 0/26 (0%) | 0/38 (0%) | |||||
| Fall | 1/30 (3.3%) | 2/24 (8.3%) | 1/27 (3.7%) | 3/26 (11.5%) | 2/38 (5.3%) | |||||
| Muscle strain | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 2/26 (7.7%) | 1/38 (2.6%) | |||||
| Anastomotic stenosis | 2/30 (6.7%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Arthropod bite | 0/30 (0%) | 0/24 (0%) | 2/27 (7.4%) | 0/26 (0%) | 0/38 (0%) | |||||
| Biliary anastomosis complication | 0/30 (0%) | 0/24 (0%) | 3/27 (11.1%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Hepatic haematoma | 0/30 (0%) | 2/24 (8.3%) | 0/27 (0%) | 1/26 (3.8%) | 2/38 (5.3%) | |||||
| Incision site pain | 5/30 (16.7%) | 2/24 (8.3%) | 2/27 (7.4%) | 4/26 (15.4%) | 6/38 (15.8%) | |||||
| Wound complication | 3/30 (10%) | 0/24 (0%) | 1/27 (3.7%) | 1/26 (3.8%) | 3/38 (7.9%) | |||||
| Wound secretion | 0/30 (0%) | 0/24 (0%) | 2/27 (7.4%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Incision site haemorrhage | 2/30 (6.7%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 1/38 (2.6%) | |||||
| Post procedural discharge | 2/30 (6.7%) | 0/24 (0%) | 3/27 (11.1%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Spinal fracture | 0/30 (0%) | 2/24 (8.3%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Tooth fracture | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 2/26 (7.7%) | 0/38 (0%) | |||||
| Investigations | ||||||||||
| Platelet count decreased | 2/30 (6.7%) | 1/24 (4.2%) | 0/27 (0%) | 1/26 (3.8%) | 1/38 (2.6%) | |||||
| Blood glucose increased | 2/30 (6.7%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 5/38 (13.2%) | |||||
| Blood pressure increased | 2/30 (6.7%) | 1/24 (4.2%) | 0/27 (0%) | 1/26 (3.8%) | 1/38 (2.6%) | |||||
| Gamma-glutamyltransferase increased | 1/30 (3.3%) | 2/24 (8.3%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Urine output decreased | 2/30 (6.7%) | 0/24 (0%) | 1/27 (3.7%) | 4/26 (15.4%) | 2/38 (5.3%) | |||||
| White blood cell count increased | 0/30 (0%) | 0/24 (0%) | 3/27 (11.1%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Bacterial test positive | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 3/38 (7.9%) | |||||
| Blood potassium increased | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 3/26 (11.5%) | 1/38 (2.6%) | |||||
| Liver function test abnormal | 6/30 (20%) | 1/24 (4.2%) | 3/27 (11.1%) | 9/26 (34.6%) | 7/38 (18.4%) | |||||
| Staphylococcus test positive | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 2/26 (7.7%) | 1/38 (2.6%) | |||||
| Breath sounds abnormal | 3/30 (10%) | 2/24 (8.3%) | 3/27 (11.1%) | 3/26 (11.5%) | 3/38 (7.9%) | |||||
| C-reactive protein increased | 0/30 (0%) | 1/24 (4.2%) | 2/27 (7.4%) | 1/26 (3.8%) | 1/38 (2.6%) | |||||
| Weight increased | 5/30 (16.7%) | 6/24 (25%) | 2/27 (7.4%) | 6/26 (23.1%) | 3/38 (7.9%) | |||||
| White blood cell count decreased | 3/30 (10%) | 1/24 (4.2%) | 1/27 (3.7%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Aspartate aminotransferase increased | 1/30 (3.3%) | 2/24 (8.3%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Blood bilirubin increased | 4/30 (13.3%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Enterococcus test positive | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 2/26 (7.7%) | 1/38 (2.6%) | |||||
| Transaminases increased | 3/30 (10%) | 1/24 (4.2%) | 3/27 (11.1%) | 0/26 (0%) | 0/38 (0%) | |||||
| Alanine aminotransferase increased | 0/30 (0%) | 2/24 (8.3%) | 1/27 (3.7%) | 1/26 (3.8%) | 1/38 (2.6%) | |||||
| Blood alkaline phosphatase increased | 3/30 (10%) | 1/24 (4.2%) | 2/27 (7.4%) | 0/26 (0%) | 0/38 (0%) | |||||
| Blood triglycerides increased | 2/30 (6.7%) | 2/24 (8.3%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Blood creatinine increased | 5/30 (16.7%) | 1/24 (4.2%) | 2/27 (7.4%) | 6/26 (23.1%) | 8/38 (21.1%) | |||||
| Blood magnesium decreased | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Body temperature increased | 2/30 (6.7%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Clostridium test positive | 0/30 (0%) | 0/24 (0%) | 2/27 (7.4%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Hepatic enzyme increased | 5/30 (16.7%) | 4/24 (16.7%) | 4/27 (14.8%) | 1/26 (3.8%) | 4/38 (10.5%) | |||||
| Weight decreased | 3/30 (10%) | 3/24 (12.5%) | 1/27 (3.7%) | 3/26 (11.5%) | 4/38 (10.5%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Hypermagnesaemia | 3/30 (10%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Decreased appetite | 4/30 (13.3%) | 4/24 (16.7%) | 3/27 (11.1%) | 6/26 (23.1%) | 6/38 (15.8%) | |||||
| Dyslipidaemia | 0/30 (0%) | 3/24 (12.5%) | 2/27 (7.4%) | 2/26 (7.7%) | 2/38 (5.3%) | |||||
| Hyperlipidaemia | 1/30 (3.3%) | 0/24 (0%) | 3/27 (11.1%) | 3/26 (11.5%) | 1/38 (2.6%) | |||||
| Hyperphosphataemia | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 2/26 (7.7%) | 0/38 (0%) | |||||
| Hypocalcaemia | 2/30 (6.7%) | 0/24 (0%) | 1/27 (3.7%) | 1/26 (3.8%) | 1/38 (2.6%) | |||||
| Hyponatraemia | 2/30 (6.7%) | 1/24 (4.2%) | 4/27 (14.8%) | 1/26 (3.8%) | 1/38 (2.6%) | |||||
| Gout | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 3/26 (11.5%) | 0/38 (0%) | |||||
| Hyperkalaemia | 5/30 (16.7%) | 2/24 (8.3%) | 3/27 (11.1%) | 8/26 (30.8%) | 8/38 (21.1%) | |||||
| Hypoalbuminaemia | 2/30 (6.7%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Hypophosphataemia | 3/30 (10%) | 1/24 (4.2%) | 2/27 (7.4%) | 0/26 (0%) | 0/38 (0%) | |||||
| Hypovolaemia | 1/30 (3.3%) | 0/24 (0%) | 2/27 (7.4%) | 1/26 (3.8%) | 1/38 (2.6%) | |||||
| Metabolic acidosis | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 2/38 (5.3%) | |||||
| Vitamin D deficiency | 2/30 (6.7%) | 1/24 (4.2%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Diabetes mellitus | 2/30 (6.7%) | 4/24 (16.7%) | 2/27 (7.4%) | 3/26 (11.5%) | 9/38 (23.7%) | |||||
| Hyperuricaemia | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 3/38 (7.9%) | |||||
| Hypomagnesaemia | 4/30 (13.3%) | 1/24 (4.2%) | 4/27 (14.8%) | 6/26 (23.1%) | 8/38 (21.1%) | |||||
| Dehydration | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 1/26 (3.8%) | 3/38 (7.9%) | |||||
| Fluid overload | 1/30 (3.3%) | 1/24 (4.2%) | 2/27 (7.4%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Hyperglycaemia | 11/30 (36.7%) | 5/24 (20.8%) | 9/27 (33.3%) | 5/26 (19.2%) | 9/38 (23.7%) | |||||
| Hypercholesterolaemia | 2/30 (6.7%) | 2/24 (8.3%) | 1/27 (3.7%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Hypertriglyceridaemia | 1/30 (3.3%) | 0/24 (0%) | 1/27 (3.7%) | 2/26 (7.7%) | 1/38 (2.6%) | |||||
| Hypoglycaemia | 4/30 (13.3%) | 0/24 (0%) | 4/27 (14.8%) | 1/26 (3.8%) | 2/38 (5.3%) | |||||
| Hypokalaemia | 6/30 (20%) | 9/24 (37.5%) | 8/27 (29.6%) | 3/26 (11.5%) | 8/38 (21.1%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Intervertebral disc protrusion | 1/30 (3.3%) | 0/24 (0%) | 2/27 (7.4%) | 0/26 (0%) | 0/38 (0%) | |||||
| Osteopenia | 2/30 (6.7%) | 1/24 (4.2%) | 2/27 (7.4%) | 1/26 (3.8%) | 3/38 (7.9%) | |||||
| Arthralgia | 6/30 (20%) | 5/24 (20.8%) | 4/27 (14.8%) | 8/26 (30.8%) | 6/38 (15.8%) | |||||
| Pain in extremity | 5/30 (16.7%) | 5/24 (20.8%) | 5/27 (18.5%) | 7/26 (26.9%) | 6/38 (15.8%) | |||||
| Back pain | 10/30 (33.3%) | 7/24 (29.2%) | 9/27 (33.3%) | 6/26 (23.1%) | 11/38 (28.9%) | |||||
| Muscle spasms | 5/30 (16.7%) | 3/24 (12.5%) | 3/27 (11.1%) | 2/26 (7.7%) | 7/38 (18.4%) | |||||
| Muscular weakness | 1/30 (3.3%) | 1/24 (4.2%) | 1/27 (3.7%) | 4/26 (15.4%) | 3/38 (7.9%) | |||||
| Pain in jaw | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 2/26 (7.7%) | 0/38 (0%) | |||||
| Flank pain | 1/30 (3.3%) | 0/24 (0%) | 2/27 (7.4%) | 3/26 (11.5%) | 0/38 (0%) | |||||
| Musculoskeletal chest pain | 1/30 (3.3%) | 2/24 (8.3%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Neck pain | 1/30 (3.3%) | 2/24 (8.3%) | 4/27 (14.8%) | 0/26 (0%) | 3/38 (7.9%) | |||||
| Osteoporosis | 0/30 (0%) | 2/24 (8.3%) | 0/27 (0%) | 1/26 (3.8%) | 3/38 (7.9%) | |||||
| Arthritis | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 2/26 (7.7%) | 2/38 (5.3%) | |||||
| Joint swelling | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 2/26 (7.7%) | 1/38 (2.6%) | |||||
| Musculoskeletal stiffness | 0/30 (0%) | 0/24 (0%) | 2/27 (7.4%) | 0/26 (0%) | 0/38 (0%) | |||||
| Myalgia | 3/30 (10%) | 0/24 (0%) | 2/27 (7.4%) | 2/26 (7.7%) | 2/38 (5.3%) | |||||
| Osteoarthritis | 1/30 (3.3%) | 2/24 (8.3%) | 1/27 (3.7%) | 1/26 (3.8%) | 1/38 (2.6%) | |||||
| Musculoskeletal pain | 2/30 (6.7%) | 3/24 (12.5%) | 1/27 (3.7%) | 3/26 (11.5%) | 3/38 (7.9%) | |||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Haemangioma of liver | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Seborrhoeic keratosis | 2/30 (6.7%) | 0/24 (0%) | 2/27 (7.4%) | 0/26 (0%) | 0/38 (0%) | |||||
| Melanocytic naevus | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Nervous system disorders | ||||||||||
| Hypoaesthesia | 3/30 (10%) | 2/24 (8.3%) | 3/27 (11.1%) | 4/26 (15.4%) | 2/38 (5.3%) | |||||
| Facial paresis | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Neuropathy peripheral | 1/30 (3.3%) | 1/24 (4.2%) | 1/27 (3.7%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Tremor | 1/30 (3.3%) | 3/24 (12.5%) | 2/27 (7.4%) | 10/26 (38.5%) | 14/38 (36.8%) | |||||
| Hyporeflexia | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 2/38 (5.3%) | |||||
| Lethargy | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 3/38 (7.9%) | |||||
| Neuralgia | 0/30 (0%) | 1/24 (4.2%) | 0/27 (0%) | 0/26 (0%) | 3/38 (7.9%) | |||||
| Dizziness | 6/30 (20%) | 1/24 (4.2%) | 4/27 (14.8%) | 3/26 (11.5%) | 4/38 (10.5%) | |||||
| Headache | 12/30 (40%) | 4/24 (16.7%) | 9/27 (33.3%) | 14/26 (53.8%) | 10/38 (26.3%) | |||||
| Migraine | 0/30 (0%) | 1/24 (4.2%) | 1/27 (3.7%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Carpal tunnel syndrome | 0/30 (0%) | 0/24 (0%) | 2/27 (7.4%) | 0/26 (0%) | 0/38 (0%) | |||||
| Paraesthesia | 3/30 (10%) | 0/24 (0%) | 1/27 (3.7%) | 2/26 (7.7%) | 3/38 (7.9%) | |||||
| Amnesia | 2/30 (6.7%) | 0/24 (0%) | 0/27 (0%) | 2/26 (7.7%) | 2/38 (5.3%) | |||||
| Convulsion | 0/30 (0%) | 1/24 (4.2%) | 1/27 (3.7%) | 1/26 (3.8%) | 2/38 (5.3%) | |||||
| Memory impairment | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 3/38 (7.9%) | |||||
| Psychiatric disorders | ||||||||||
| Insomnia | 7/30 (23.3%) | 5/24 (20.8%) | 8/27 (29.6%) | 9/26 (34.6%) | 8/38 (21.1%) | |||||
| Mental status changes | 1/30 (3.3%) | 0/24 (0%) | 2/27 (7.4%) | 2/26 (7.7%) | 0/38 (0%) | |||||
| Mood swings | 1/30 (3.3%) | 1/24 (4.2%) | 0/27 (0%) | 2/26 (7.7%) | 1/38 (2.6%) | |||||
| Agitation | 2/30 (6.7%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Hallucination | 2/30 (6.7%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Confusional state | 3/30 (10%) | 0/24 (0%) | 1/27 (3.7%) | 2/26 (7.7%) | 0/38 (0%) | |||||
| Transient psychosis | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 2/38 (5.3%) | |||||
| Anxiety | 7/30 (23.3%) | 1/24 (4.2%) | 3/27 (11.1%) | 6/26 (23.1%) | 7/38 (18.4%) | |||||
| Depression | 10/30 (33.3%) | 4/24 (16.7%) | 2/27 (7.4%) | 6/26 (23.1%) | 5/38 (13.2%) | |||||
| Sleep disorder | 0/30 (0%) | 1/24 (4.2%) | 2/27 (7.4%) | 3/26 (11.5%) | 2/38 (5.3%) | |||||
| Renal and urinary disorders | ||||||||||
| Dysuria | 0/30 (0%) | 2/24 (8.3%) | 4/27 (14.8%) | 1/26 (3.8%) | 2/38 (5.3%) | |||||
| Nocturia | 1/30 (3.3%) | 1/24 (4.2%) | 2/27 (7.4%) | 2/26 (7.7%) | 1/38 (2.6%) | |||||
| Urinary retention | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 3/38 (7.9%) | |||||
| Proteinuria | 4/30 (13.3%) | 1/24 (4.2%) | 1/27 (3.7%) | 4/26 (15.4%) | 0/38 (0%) | |||||
| Renal failure acute | 2/30 (6.7%) | 0/24 (0%) | 2/27 (7.4%) | 2/26 (7.7%) | 8/38 (21.1%) | |||||
| Renal tubular necrosis | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 2/38 (5.3%) | |||||
| Haematuria | 2/30 (6.7%) | 1/24 (4.2%) | 1/27 (3.7%) | 1/26 (3.8%) | 1/38 (2.6%) | |||||
| Pollakiuria | 0/30 (0%) | 1/24 (4.2%) | 2/27 (7.4%) | 0/26 (0%) | 0/38 (0%) | |||||
| Renal impairment | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 5/26 (19.2%) | 2/38 (5.3%) | |||||
| Nephrolithiasis | 2/30 (6.7%) | 0/24 (0%) | 0/27 (0%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Renal failure | 0/30 (0%) | 1/24 (4.2%) | 2/27 (7.4%) | 5/26 (19.2%) | 5/38 (13.2%) | |||||
| Urinary incontinence | 1/30 (3.3%) | 1/24 (4.2%) | 0/27 (0%) | 2/26 (7.7%) | 1/38 (2.6%) | |||||
| Oliguria | 2/30 (6.7%) | 1/24 (4.2%) | 1/27 (3.7%) | 4/26 (15.4%) | 1/38 (2.6%) | |||||
| Reproductive system and breast disorders | ||||||||||
| Erectile dysfunction | 0/30 (0%) | 0/24 (0%) | 2/27 (7.4%) | 2/26 (7.7%) | 1/38 (2.6%) | |||||
| Scrotal oedema | 2/30 (6.7%) | 2/24 (8.3%) | 0/27 (0%) | 1/26 (3.8%) | 2/38 (5.3%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Atelectasis | 5/30 (16.7%) | 1/24 (4.2%) | 3/27 (11.1%) | 2/26 (7.7%) | 1/38 (2.6%) | |||||
| Pulmonary hypertension | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 2/26 (7.7%) | 0/38 (0%) | |||||
| Rhonchi | 0/30 (0%) | 2/24 (8.3%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Oropharyngeal pain | 0/30 (0%) | 2/24 (8.3%) | 5/27 (18.5%) | 2/26 (7.7%) | 7/38 (18.4%) | |||||
| Rhinitis allergic | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Stridor | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Cough | 12/30 (40%) | 2/24 (8.3%) | 8/27 (29.6%) | 3/26 (11.5%) | 6/38 (15.8%) | |||||
| Dyspnoea | 5/30 (16.7%) | 5/24 (20.8%) | 6/27 (22.2%) | 7/26 (26.9%) | 5/38 (13.2%) | |||||
| Pulmonary oedema | 1/30 (3.3%) | 1/24 (4.2%) | 3/27 (11.1%) | 3/26 (11.5%) | 2/38 (5.3%) | |||||
| Sinus congestion | 2/30 (6.7%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
| Wheezing | 2/30 (6.7%) | 1/24 (4.2%) | 2/27 (7.4%) | 3/26 (11.5%) | 0/38 (0%) | |||||
| Paranasal sinus hypersecretion | 0/30 (0%) | 1/24 (4.2%) | 2/27 (7.4%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Hypoxia | 1/30 (3.3%) | 0/24 (0%) | 0/27 (0%) | 2/26 (7.7%) | 0/38 (0%) | |||||
| Pleural effusion | 7/30 (23.3%) | 5/24 (20.8%) | 6/27 (22.2%) | 8/26 (30.8%) | 10/38 (26.3%) | |||||
| Productive cough | 4/30 (13.3%) | 2/24 (8.3%) | 1/27 (3.7%) | 2/26 (7.7%) | 1/38 (2.6%) | |||||
| Respiratory failure | 1/30 (3.3%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Rhinorrhoea | 4/30 (13.3%) | 1/24 (4.2%) | 3/27 (11.1%) | 2/26 (7.7%) | 1/38 (2.6%) | |||||
| Dyspnoea exertional | 2/30 (6.7%) | 0/24 (0%) | 1/27 (3.7%) | 4/26 (15.4%) | 3/38 (7.9%) | |||||
| Nasal congestion | 1/30 (3.3%) | 1/24 (4.2%) | 2/27 (7.4%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Rales | 1/30 (3.3%) | 1/24 (4.2%) | 0/27 (0%) | 2/26 (7.7%) | 1/38 (2.6%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Actinic keratosis | 2/30 (6.7%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Hyperhidrosis | 2/30 (6.7%) | 0/24 (0%) | 2/27 (7.4%) | 1/26 (3.8%) | 1/38 (2.6%) | |||||
| Alopecia | 4/30 (13.3%) | 1/24 (4.2%) | 2/27 (7.4%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Ecchymosis | 2/30 (6.7%) | 0/24 (0%) | 1/27 (3.7%) | 1/26 (3.8%) | 3/38 (7.9%) | |||||
| Pruritus | 5/30 (16.7%) | 1/24 (4.2%) | 3/27 (11.1%) | 8/26 (30.8%) | 10/38 (26.3%) | |||||
| Skin exfoliation | 2/30 (6.7%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Rash | 5/30 (16.7%) | 2/24 (8.3%) | 4/27 (14.8%) | 5/26 (19.2%) | 5/38 (13.2%) | |||||
| Eczema | 0/30 (0%) | 3/24 (12.5%) | 3/27 (11.1%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Increased tendency to bruise | 0/30 (0%) | 0/24 (0%) | 2/27 (7.4%) | 1/26 (3.8%) | 0/38 (0%) | |||||
| Night sweats | 3/30 (10%) | 1/24 (4.2%) | 3/27 (11.1%) | 2/26 (7.7%) | 1/38 (2.6%) | |||||
| Rash erythematous | 0/30 (0%) | 0/24 (0%) | 2/27 (7.4%) | 0/26 (0%) | 0/38 (0%) | |||||
| Pigmentation disorder | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Skin discolouration | 2/30 (6.7%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 0/38 (0%) | |||||
| Dermatitis | 1/30 (3.3%) | 2/24 (8.3%) | 2/27 (7.4%) | 0/26 (0%) | 0/38 (0%) | |||||
| Vascular disorders | ||||||||||
| Intra-abdominal haemorrhage | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 2/26 (7.7%) | 0/38 (0%) | |||||
| Venous thrombosis limb | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Haematoma | 1/30 (3.3%) | 1/24 (4.2%) | 2/27 (7.4%) | 1/26 (3.8%) | 3/38 (7.9%) | |||||
| Lymphocele | 2/30 (6.7%) | 0/24 (0%) | 0/27 (0%) | 0/26 (0%) | 1/38 (2.6%) | |||||
| Haemorrhage | 0/30 (0%) | 0/24 (0%) | 0/27 (0%) | 2/26 (7.7%) | 0/38 (0%) | |||||
| Hypotension | 5/30 (16.7%) | 1/24 (4.2%) | 7/27 (25.9%) | 6/26 (23.1%) | 7/38 (18.4%) | |||||
| Flushing | 0/30 (0%) | 0/24 (0%) | 1/27 (3.7%) | 0/26 (0%) | 2/38 (5.3%) | |||||
| Hypertension | 5/30 (16.7%) | 6/24 (25%) | 6/27 (22.2%) | 11/26 (42.3%) | 16/38 (42.1%) | |||||
| Hot flush | 4/30 (13.3%) | 1/24 (4.2%) | 1/27 (3.7%) | 0/26 (0%) | 0/38 (0%) | |||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Results Point of Contact
| Name/Title | BMS Study Director |
|---|---|
| Organization | Bristol-Myers Squibb |
| Phone | |
| Clinical.Trials@bms.com |
Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00555321
Other Study ID Numbers:
- IM103-045
First Posted:
Nov 8, 2007
Last Update Posted:
Oct 18, 2012
Last Verified:
Sep 1, 2012