Study to Assess Steady-State Trough Concentrations, Safety, and Immunogenicity of Abatacept After Subcutaneous (SC) Administration to Subjects With Rheumatoid Arthritis (RA)
Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT00254293
Collaborator
(none)
87
5
6
78
17.4
0.2
Study Details
Study Description
Brief Summary
The purpose of this study is to study serum levels of Abatacept after subcutaneous dosing in subjects with RA.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
87 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Study to Assess the Steady-State Trough Serum Concentration, Safety, and Immunogenicity of Abatacept (BMS-188667) Administered Subcutaneously in Subjects With Active Rheumatoid Arthritis Who Are Receiving Disease Modifying Ant-Rheumatic Drugs (DMARDs)
Study Start Date
:
Jan 1, 2006
Actual Primary Completion Date
:
May 1, 2007
Actual Study Completion Date
:
Jul 1, 2012
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Group 1 (weight < 60 kg)
|
Drug: Abatacept or Placebo (both as IV & SC Solution)
Abatacept & Placebo as IV & SC solution, IV/SC, Abatacept 500 mg IV (Day 1)/Abatacept 75 mg SC (once weekly for 12 weeks) or Placebo IV(Day 1)/Placebo SC (once weekly for 12 weeks), 12 weeks then long term extension (LTE).
Other Names:
|
| Placebo Comparator: Group 2 (weight < 60 kg)
|
Drug: Abatacept or Placebo (both as IV & SC Solution)
Abatacept & Placebo as IV & SC solution, IV/SC, Abatacept 500 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks) or Placebo IV(Day 1)/Placebo SC (once weekly for 12 weeks), 12 weeks then long term extension (LTE).
Other Names:
|
| Placebo Comparator: Group 3 (weight 60-100 kg)
|
Drug: Abatacept or Placebo (both as IV & SC solution)
Abatacept & Placebo as IV & SC solution, IV/SC, Abatacept 750 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks) or Placebo IV(Day 1)/Placebo SC (once weekly for 12 weeks), 12 weeks then long term extension (LTE).
Other Names:
|
| Placebo Comparator: Group 4 (weight > 100 kg)
|
Drug: Abatacept or Placebo (both as IV & SC solution)
Abatacept & Placebo as IV & SC solution, IV/SC, Abatacept 1000 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks) or Placebo IV(Day 1)/Placebo SC (once weekly for 12 weeks), 12 weeks then long term extension (LTE).
Other Names:
|
| Placebo Comparator: Group 5 (weight > 100 kg)
|
Drug: Abatacept or Placebo (both as IV & SC solution)
Abatacept & Placebo as IV & SC solution, IV/SC, Abatacept 1000 mg IV (Day 1)/Abatacept 200 mg SC (once weekly for 12 weeks) or Placebo IV(Day 1)/Placebo SC (once weekly for 12 weeks), 12 weeks then long term extension (LTE).
Other Names:
|
| Experimental: Abatacept Long Term |
Drug: Abatacept
Solution in pre-filled syringes, Subcutaneously, 125 mg, Weekly
|
Outcome Measures
Primary Outcome Measures
- Short Term Period: Steady-state Trough Serum Concentration (Cmin) of Abatacept Following Weekly Subcutaneous Dosing in Participants With Active Rheumatoid Arthritis Receiving Disease Modifying Anti-rheumatic Drugs (DMARDS) [Days 71 to 85]
Participants received abatacept while also receiving DMARDS over a short term (ST) 12 Week period. To eliminate contribution from the IV loading dose of abatacept during the short term study period, Cmin values were selected from Days 71 to 85, when contribution from IV was negligible. Minimum trough serum concentration of abatacept (Cmin) was measured in micrograms/milliliter (µg/mL). Data are presented by treatment the participant actually received, not by what they were randomized to receive.
- Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Discontinuations Due to Adverse Events Reported During the Variable Dosing Phase of the Long Term Period (LTE) [Day 85 to 56 days post last dose]
AEs during variable dose phase of LTE + 56 days post last dose in the variable dose phase or start of the fixed dose phase, which ever came first; includes deaths reported during the variable dose phase including those that occurred greater than 56 days after last dose. Medical Dictionary for Regulatory Activities (MedDRA) version: 15.1. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization (included hospitalizations for elective surgical procedures). Treatment-related=having certain, probable, possible, or missing relationship to study drug. Data presented by treatment the participant was randomized to and not what they actually received.
- Number of Participants With Pre-specified AEs of Special Interest in the Variable Dosing Phase of Long Term Extension (LTE) [Day 85 to Day 533]
LTE period with variable abatacept dosing starting on Day 85 and continuing until Day 533 when LTE fixed dosing started. AEs of special interest: infection and/or infestation; neoplasms (malignant); pre-specified autoimmune disorder; infusional AEs (peri-infusional: pre-specified AEs occurring during first 24 hours (hrs) after start of the IV loading dose; acute infusional: pre-specified AEs occurring during the first hour after the start of the IV loading dose; systemic injection site reactions (SIR): pre-specified AEs for SIR; local injection site reaction: pre-specified AEs for local site reaction. Data are presented by treatment the participant was randomized to and not what they actually received.
- Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Discontinuations Due to Adverse Events Summarized Over the Entire Long Term Extension (LTE) Period (Both Variable and Fixed Dosing) [Day 533 to 56 Days Post last dose]
On Day 85 participants rolled over into the LTE with variable dose phase first and at Day 533, a fixed dose phase of 125 mg abatacept SC weekly, irrespective of body weight. This summary includes AEs reported during entire LTE treatment plus 56 days post last dose; includes all deaths reported during the LTE including those that occurred greater than 56 days after last dose. MedDRA version: 15.1. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization (also included hospitalizations for elective surgical procedures). Treatment-related=having certain, probable, possible, or missing relationship to study drug.
Secondary Outcome Measures
- Short Term Period: Peak Serum Concentration (Cmax) of Abatacept at Steady State in Participants With Rheumatoid Arthritis Receiving DMARDS [Day 71 to Day 78]
Peak serum concentration (Cmax) of abatacept after weekly SC administration was determined between the SC dosing interval from Day 71 to 78. Abatacept in human serum was measured by enzyme-linked immunosorbent assay (ELISA). Lower limit of quantification (LLOQ) was 0.001, Upper limit of quantification (ULOQ) was 0.030. Cmax measured in micrograms per milliliter(µg/mL). Data are presented by treatment the participant actually received, not by what they were randomized to receive.
- Short Term Period: Area Under the Curve (AUC) in Time Interval of 7 Days [AUC(TAU)] of Abatacept in Participants With Rheumatoid Arthritis Receiving DMARDS [Day 71 to Day 78]
The steady-state pharmacokinetic parameter AUC(TAU) of abatacept after weekly SC administration was determined between the SC dosing interval from Day 71 to 78 (TAU=7 days). Abatacept in human serum was measured by enzyme-linked immunosorbent assay (ELISA). Lower limit of quantification (LLOQ) was 0.001; Upper limit of quantification (ULOQ) was 0.030. AUC(TAU) measured in in micrograms*hours per milliliter (µg*h/mL). Data are presented by treatment the participant actually received, not by what they were randomized to receive.
- Short Term Period: Summary of Adverse Events (AEs), Serious AEs, Deaths, and Discontinuations Due to AEs During 12 Weeks of Treatment With Either Abatacept or Placebo [Day 1 to Day 85 (or early termination)]
Number of Participants with Adverse events (AEs), Serious AEs, discontinuations due to AEs, or Deaths occurring while participant was on treatment from Day 1 (treatment) to Day 85 or early termination from the study. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization (also included hospitalizations for elective surgical procedures). Data are presented by treatment the participant actually received, not by what they were randomized to receive.
- Short Term Period: Number of Participants With Pre-specified Adverse Events (AEs) of Special Interest After Administration of Abatacept or Placebo Over 12 Weeks [Day 1 to Day 85 (or early termination)]
AEs of special interest: infection and/or infestation; neoplasms (benign, malignant, unspecified; autoimmune disorder; infusional AEs (peri-infusional: AEs occurring during first 24 hours (hrs) after start of the IV loading dose; acute infusional: AEs occurring during the first hour after the start of the IV loading dose; injection site AEs: AEs occurring at the site of the SC injection. Data are presented by treatment the participant actually received, not by what they were randomized to receive.
- Short Term Period: Mean Percent Change From Baseline on Day 85 in Participants Positive for Serum Rheumatoid Factor During Abatacept or Placebo Administration [Day 1 to Day 85 (or early termination)]
Serum samples were obtained on Days 1, 8, 15, 29, 57 and day of discharge (Day 85 or earlier) for determination of presence of rheumatoid factor (RF). Baseline was defined as Day 1 to calculate percent change. Lower limit of quantitation (LLQ) was 5 Units/milliliter (U/mL). Values below LLQ were set to 2.5 U/mL. Data are presented by treatment the participant actually received, not by what they were randomized to receive.
- Short Term Period: Number of Participants With Laboratory Abnormalities in Hematology at Baseline (Day 1) to End of Period (Day 85) [Day 1 to Day 85 (or early termination)]
Blood samples were obtained: At screening, within 24 hours prior to study drug administration on Day 1, on Days 15, 29, 57 and at study discharge. Baseline (BL) defined as Day 1 prior to treatment. Common toxicity criteria (CTC), Version 3 used to assess parameters. lower limit of normal (LLN). ANC=absolute neutrophil count. White blood cells Grade (Gr) 1:<LLN to 3.0*10^9/L, Gr 2:<3.0 to 2.0*10^9/L, Gr 3:<2.0 to 1.0*10^9/L, Gr 4:<1.0*10^9/L. ANC Gr 1:<LLN to 1.5*10^9/L, Gr 2:<1.5 to 1.0*10^9/L, Gr 3:<1.0 to 0.5*10^9/L, Gr 4:<0.5*10^9/L. Lymphocytes Gr 1: <LLN to 3.0, Gr 2: 2.0 < 3.0, Gr 3: 1.0 to < 2.0, Gr 4; < 1.0. Platelet count Gr 1:LLN to 75.0*10^9/L, Gr 2:<75.0 to 50.0*10^9/L, Gr 3:<50.0 to 25.0*10^9/L, Gr 4:<25.0 to 10^9/L. Hemoglobin Gr 1:<LLN to 10.0 g/dL, Gr 2:<10.0 to 8.0 g/dL, Gr 3:<8.0 to 6.5 g/dL, Gr 4:<6.5 g/dL. Hematocrit (%): <0.75*pre-treatment. Data are presented by treatment the participant actually received, not by what they were randomized to receive.
- Short Term Period: Number of Participants With Laboratory Abnormalities in Serum Chemistry at Baseline and on Treatment up to Day 85 [Day 1 to Day 85 (or early termination)]
Screening, BL, Days 15, 29, 57, 85 or discharge. Upper limit of normal (ULN). CTC grade (Gr): Alanine transaminase Gr 1:>ULN to 2.5*ULN; Gr 2: >2.5 to 5.0*ULN; Gr 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. Aspartate aminotransferase Gr 1: >ULN to 2.5*ULN; Gr 2:>2.5 to 5.0*ULN; Gr 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. G-Glutamyl Transferase (U/L) Gr 1:>ULN to 2.5*ULN; Gr 2: >2.5 to 5.0*ULN; Gr 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. Alkaline phosphatase (U/L) Gr 1:>ULN to 2.5*ULN, Gr2:>2.5 to 5.0*ULN, Gr3:>5.0 to 20.0*ULN, Gr4: >20.0*ULN; creatinine (mg/dL) Gr 1: >ULN to 1.5*ULN; Gr 2: >1.5 to 3.0*ULN; Gr 3: >3.0 to 6.0*ULN; Gr 4: >10.0*ULN. Albumin (g/dL) Gr 1:<LLN to 3.0; Gr 2:<3.0 to 2.0; Gr 3: <2.0. Uric Acid (mg/dL)Gr 1: >1.0 x ULN to 10.0; Gr 4: >10.0. Sodium (mEq/L) Gr 1: >ULN to 150; Gr 2: >150 to 155; Gr 3: >155 to 160; Gr 4: > 160. Potassium (mEq/L) Gr 1: >ULN to 5.5; Gr 2: >5.5 to 6.0; Gr 3: >6.0 to 7.0; Gr 4: >7.0. Data presented by treatment participant actually received.
- Short Term Period: Mean Change From Baseline at Day 85 in Blood Pressure After SC Administration of Abatacept or Placebo in Participants With Rheumatoid Arthritis Receiving DMARDS [Day 1 to Day 85 (or early termination)]
Blood pressure (systolic and diastolic) was recorded while the participant was seated during the screening visit, at baseline on Day 1 (prior to administration of IV infusion), prior to administration of all SC injections, and at study discharge (Day 85 or 7 days after the last dose for subjects who terminated early). In addition, blood pressure was recorded at 30 and 60 minutes after the start of the IV infusion on Day 1, and 30 and 60 minutes after all SC injections. Blood pressure was measured in millimeters of mercury (mm Hg). Data are presented by treatment the participant actually received, not by what they were randomized to receive.
- Short Term Period: Mean Change From Baseline at Day 85 in Pulse Rate After SC Administration of Abatacept or Placebo in Participants With Rheumatoid Arthritis Receiving DMARDS [Day 1 to Day 85 (or early termination)]
Pulse rate was taken while participant was seated. Pulse rate was recorded during the screening visit, at baseline on Day 1 (prior to administration of IV infusion), prior to administration of all SC injections, and at study discharge (Day 85 or 7 days after the last dose for subjects who terminated early). In addition, vital signs were recorded at 30 and 60 minutes after the start of the IV infusion on Day 1, and 30 and 60 minutes after all SC injections. Pulse rate measured in beats/min (bpm). Data are presented by treatment the participant actually received, not by what they were randomized to receive.
- Short Term Period: Mean Change From Screening to Day 85 in Electrocardiogram (QT, PR Intervals, QRS Width) After SC Administration of Abatacept or Placebo in Participants With Rheumatoid Arthritis Receiving DMARDS [Screening to Day 85 (or early termination)]
A 12-lead electrocardiogram (ECG) was recorded at screening and at discharge from the study (Day 85 or 7 days after the last dose of study drug for those subjects who terminated early). If there was no history of known cardiac events, an ECG was performed within 6 months of study entry, and documentation was on file, then the screening ECG was not repeated at screening. QT interval, PR interval and QRW Width were reported in milliseconds (msec). If no ECG issues were found in the 12 weeks of the Short Term Period, ECG was not repeated during LTE. Data are presented by treatment the participant actually received, not by what they were randomized to receive.
- Short Term Period: Mean Change From Screening at Day 85 in ECG (Heart Rate) After SC Administration of Abatacept or Placebo in Participants With Rheumatoid Arthritis Receiving DMARDS [Screening to Day 85 (or early termination)]
A 12-lead electrocardiogram (ECG) was recorded at screening and at discharge from the study (Day 85 or 7 days after the last dose of study drug for those subjects who terminated early). If there was no history of known cardiac events, an ECG was performed within 6 months of study entry, and documentation was on file, then the screening ECG was not repeated at screening. Heart Rate was reported in beats per minute (bpm). In no ECG issues were found in the 12 weeks of the Short Term Period, ECG was not repeated during LTE. Data are presented by treatment the participant actually received, not by what they were randomized to receive.
- Overall Study ST and LTE Periods: Number of Participants With Anti-abatacept Antibodies and/or Anti-cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Antibodies [ST: Day 1 to Day 85; LTE: Day 85 to 168 days post last dose]
Assessment of positive antibody response based upon analysis using a validated enzyme-linked immunosorbent assay (ELISA) with a cut-off value. CTLA4 is a protein receptor that downregulates the immune system. Short Term (ST) period was initial 12 Weeks of the study. Overall LTE includes both the variable and fixed abatacept dosing periods and was from the end of the ST period (Day 85) up to 168 days post last dose (treatment in LTE ranged from 4.4 to 74.2 months. Data in the ST period are summarized by the treatment the participants actually received, while the LT period data are summarized by treatment the participant was randomized to receive.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Meet ARA criteria for diagnosis of RA with active disease.
-
RA diagnosis for at least 1 year.
-
= 6 swollen joints.
-
= 8 tender joints.
-
Taking methotrexate (MTX) or MTX plus not more than 1 added oral DMARD for > = 3 months and stable for 28 days prior to dosing.
Exclusion Criteria:
-
Serious acute or bacterial infection in last 3 months.
-
Chronic or recurrent bacterial infections.
-
History of TB within previous 3 years or old TB not adequately treated.
-
Specific lab test abnormalities
-
History of cancer within 5 years.
-
Exposure to CTLA4Ig (Cytotoxic T-lymphocyte (T-cell)-associated antigen 4Ig), belatacept, rituximab, efalizumab, alefacept, or other investigational drug or biologic.
-
Treatment with hydroxychloroquine, azathioprine, leflunomide, immunoadsorption columns, mycophenolate mofetil, cyclosporine, D-Penicillamine or calcineurin inhibitors.
-
Exposure to live vaccines.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Orlando Clinical Research Center | Orlando | Florida | United States | 32806 |
| 2 | Winship Cancer Institute, Emory University | Atlanta | Georgia | United States | 30322 |
| 3 | New Orleans Center For Clinical Research | New Orleans | Louisiana | United States | 70119 |
| 4 | Davita Clinical Research | Minneapolis | Minnesota | United States | 55404 |
| 5 | The Arthritis Clinic & Carolina Bone & Joint | Charlotte | North Carolina | United States | 28210 |
Sponsors and Collaborators
- Bristol-Myers Squibb
Investigators
- Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00254293
Other Study ID Numbers:
- IM101-063
First Posted:
Nov 16, 2005
Last Update Posted:
Apr 8, 2014
Last Verified:
Mar 1, 2014
Study Results
Participant Flow
| Recruitment Details | Short term (12 week) randomized Period: started January 2006/completed May 2007. Long term extension (LTE): started April 2006/completed July 2012. During LTE: variable dose period and fixed dose period. Patients with active Rheumatoid Arthritis (RA) and receiving disease modifying anti-rheumatic drugs (DMARDS) were eligible to participate. |
|---|---|
| Pre-assignment Detail | Enrolled/not treated (19): prior treatment not washed out; no longer met study criteria; withdrew consent before treatment. To enter LTE, participant completed the short term period, and was assigned to a variable SC dose group (75, 125, 200 mg SC abatacept) based on body weight; completers of variable dose LTE rolled over into fixed dose LTE. |
| Arm/Group Title | Group 1: 500 mg IV/75 mg SC | Group 2: 500 mg IV/125 mg SC | Group 3 : 750 mg IV/125 mg SC | Group 4: 1000mg IV/125 mg SC | Group 5: 1000 mg IV/200 mg SC | Placebo | Fixed Dose 125 mg Abatacept |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Short term (ST) randomized 12 week period: Abatacept or Placebo as intravenous (IV) and subcutaneous (SC) administration: Abatacept 500 mg IV (Day 1)/Abatacept 75 mg SC (once weekly for 12 weeks); body weight < 60 kg. Long term extension (LTE) variable dosing period: 75 mg abatacept SC administered weekly following an IV loading dose (IV abatacept for participants randomized to placebo in ST period, loading dose as described in group 1 description, or IV placebo for participants randomized to abatacept in ST period) on Day 85 (IV abatacept based on their weight at screening; < 60 kg received 500 mg abatacept IV, 60 - 100 kg received 750 mg abatacept IV, > 100 kg received 1000 mg abatacept IV for participants randomized to placebo in ST period)or, IV placebo for participants randomized to abatacept in ST period). At Day 365(1-year anniversary visit), subjects were reweighed for subsequent dosing to verify correct dosing in the variable-dose phase of the LTE period | Short term (ST) randomized 12 week period: Abatacept 500 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks) or Placebo;body weight < 60 kg. Long term extension (LTE) variable dosing period: 125 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period; loading dose described in Group 1 description, or IV placebo for participants randomized to abatacept in ST period). Variable Long term for 125 mg SC: body weight <60 to >100 kg. Participants reweighed at 1 year anniversary for subsequent dosing to verify correct dosing in the variable-dose phase of the LTE period | Short term (ST) randomized 12 week period: Abatacept 750 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks) or Placebo (body weight 60-100 kg). Long term extension (LTE) variable dosing period: 125 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period, loading dose described in Group 1 description, or IV placebo for participants randomized to abatacept in ST period). Variable Long term for 125 mg SC: body weight <60 to >100 kg). Participants reweighed at 1 year anniversary for subsequent dosing to verify correct dosing in the variable-dose phase of the LTE period. | Short term (ST) randomized 12 week period: Abatacept 1000 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks) or Placebo; Body weight > 100 kg. Long term extension (LTE) variable dosing period: 125 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period, loading dose as described in group 1 description, or IV placebo for participants randomized to abatacept in ST period); variable long term for 125 mg SC: body weight <60 to >100 kg) . Participants reweighed at 1 year anniversary for subsequent dosing to verify correct dosing in the variable-dose phase of the LTE period. | Short term (ST) randomized 12 week period: Abatacept 1000 mg IV (Day 1)/Abatacept 200 mg SC (once weekly for 12 weeks) or Placebo; body weight > 100 kg. Long term extension (LTE) variable dosing period: 200 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period, loading dose based on weight as described in Group 1 description, or IV placebo for participants randomized to abatacept in ST period). Participants reweighed at 1 year anniversary for subsequent dosing to verify correct dosing in the variable-dose phase of the LTE period | Short term (ST) randomized 12 week period: Placebo IV(Day 1)/Placebo SC (once weekly for 12 weeks), by body weight. Long term extension (LTE) variable dosing period: all placebo participants rolled over to a variable dose of abatacept SC (75, 125, 200 mg) administered weekly following an IV loading dose of abatacept on Day 85. Participants reweighed at 1 year anniversary for subsequent dosing to verify correct dosing in the variable-dose phase of the LTE period | Participants who completed the variable dose long term extension (LTE)period and received variable doses of subcutaneous (SC) abatacept (75, 125, 200 mg SC) were rolled over into the LTE with fixed dose, irrespective of body weight: SC abatacept 125 milligram (mg) in pre-filled syringes, administered Weekly. |
| Period Title: Short Term (12 Week) Randomized Dosing | |||||||
| STARTED | 7 | 4 | 29 | 6 | 5 | 17 | 0 |
| COMPLETED | 7 | 3 | 26 | 5 | 5 | 17 | 0 |
| NOT COMPLETED | 0 | 1 | 3 | 1 | 0 | 0 | 0 |
| Period Title: Short Term (12 Week) Randomized Dosing | |||||||
| STARTED | 11 | 0 | 42 | 0 | 10 | 0 | 0 |
| COMPLETED | 8 | 0 | 32 | 0 | 8 | 0 | 0 |
| NOT COMPLETED | 3 | 0 | 10 | 0 | 2 | 0 | 0 |
| Period Title: Short Term (12 Week) Randomized Dosing | |||||||
| STARTED | 0 | 0 | 0 | 0 | 0 | 0 | 48 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 35 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 13 |
Baseline Characteristics
| Arm/Group Title | Group 1: 500 mg IV/75 mg SC (Body Weight < 60 kg) | Group 2: 500 mg IV/125 mg SC (Body Weight < 60 kg) | Group 3 : 750 mg IV/125 mg SC (Body Weight 60-100 kg) | Group 4: 1000mg IV/125 mg SC (Body Weight > 100 kg) | Group 5: 1000 mg IV/200 mg SC (Body Weight > 100 kg) | Placebo | Total |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Short term (ST) randomized 12 week period: Abatacept or Placebo as intravenous (IV) and subcutaneous (SC) administration: Abatacept 500 mg IV (Day 1)/Abatacept 75 mg SC (once weekly for 12 weeks); Long term extension (LTE) variable dosing period: 75 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period, IV placebo for participants randomized to abatacept in ST period). | Short term (ST) randomized 12 week period: Abatacept 500 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks) or Placebo. Long term extension (LTE) variable dosing period: 125 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period, IV placebo for participants randomized to abatacept in ST period). | Short term (ST) randomized 12 week period: Abatacept 750 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks) or Placebo. Long term extension (LTE) variable dosing period: 125 mg abatacept SC administered weekly following an IV loading dose on Day 85 ((IV abatacept for participants randomized to placebo in ST period, IV placebo for participants randomized to abatacept in ST period). Participants from Group 3 in ST period were rolled into Group 2 for LTE variable dosing period (125 mg SC abatacept). | Short term (ST) randomized 12 week period: Abatacept 1000 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks) or Placebo. Long term extension (LTE) variable dosing period: 125 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period, IV placebo for participants randomized to abatacept in ST period). Participants from Group 4 in ST period were rolled into Group 2 for LTE variable dosing period (125 mg SC abatacept). | Short term (ST) randomized 12 week period: Abatacept 1000 mg IV (Day 1)/Abatacept 200 mg SC (once weekly for 12 weeks) or Placebo. Long term extension (LTE) variable dosing period: 200 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period, IV placebo for participants randomized to abatacept in ST period). | Short term (ST) randomized 12 week period: Placebo IV(Day 1)/Placebo SC (once weekly for 12 weeks). Long term extension (LTE) variable dosing period: all placebo participants were rolled over to a variable dose of abatacept SC administered weekly following an IV loading dose of abatacept on Day 85. | Total of all reporting groups |
| Overall Participants | 7 | 4 | 29 | 6 | 5 | 17 | 68 |
| Age (years) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [years] |
72
(5)
|
64
(10)
|
59
(12)
|
51
(9)
|
55
(9)
|
59
(11)
|
60
(11)
|
| Sex: Female, Male (Count of Participants) | |||||||
| Female |
7
100%
|
3
75%
|
26
89.7%
|
5
83.3%
|
4
80%
|
12
70.6%
|
57
83.8%
|
| Male |
0
0%
|
1
25%
|
3
10.3%
|
1
16.7%
|
1
20%
|
5
29.4%
|
11
16.2%
|
| Region of Enrollment (participants) [Number] | |||||||
| United States |
7
100%
|
4
100%
|
29
100%
|
6
100%
|
5
100%
|
17
100%
|
68
100%
|
Outcome Measures
| Title | Short Term Period: Steady-state Trough Serum Concentration (Cmin) of Abatacept Following Weekly Subcutaneous Dosing in Participants With Active Rheumatoid Arthritis Receiving Disease Modifying Anti-rheumatic Drugs (DMARDS) |
|---|---|
| Description | Participants received abatacept while also receiving DMARDS over a short term (ST) 12 Week period. To eliminate contribution from the IV loading dose of abatacept during the short term study period, Cmin values were selected from Days 71 to 85, when contribution from IV was negligible. Minimum trough serum concentration of abatacept (Cmin) was measured in micrograms/milliliter (µg/mL). Data are presented by treatment the participant actually received, not by what they were randomized to receive. |
| Time Frame | Days 71 to 85 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 50 of the 51 abatacept-treated subjects were included. One subject who discontinued after receiving only Day 1 dosing was not included in this analysis. |
| Arm/Group Title | Group 1: 500 mg IV/75 mg SC (Body Weight < 60 kg) | Group 2: 500 mg IV/125 mg SC (Body Weight < 60 kg) | Group 3 : 750 mg IV/125 mg SC (Body Weight 60-100 kg) | Group 4: 1000mg IV/125 mg SC (Body Weight > 100 kg) | Group 5: 1000 mg IV/200 mg SC (Body Weight > 100 kg) |
|---|---|---|---|---|---|
| Arm/Group Description | Subjects randomized to abatacept in group 1 received an intravenous (IV) loading dose of abatacept on Day 1 of 500 mg followed by 75 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). | Subjects randomized to abatacept in group 2 received an intravenous (IV) loading dose of abatacept on Day 1 of 500 mg followed by 125 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). | Subjects randomized to abatacept in group 3 received an intravenous (IV) loading dose of abatacept on Day 1 of 750 mg followed by 125 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). | Subjects randomized to abatacept in group 4 received an intravenous (IV) loading dose of abatacept on Day 1 of 1000 mg followed by 125 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). | Subjects randomized to abatacept in group 5 received an intravenous (IV) loading dose of abatacept on Day 1 of 1000 mg followed by 200 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). |
| Measure Participants | 7 | 4 | 29 | 5 | 5 |
| Day 71 |
22.64
(20.13)
|
28.03
(42.13)
|
24.05
(40.65)
|
16.22
(24.39)
|
26.52
(56.53)
|
| Day 78 |
21.66
(19.99)
|
34.17
(29.49)
|
24.41
(52.35)
|
11.57
(32.25)
|
29.21
(52.96)
|
| Day 85 |
23.62
(31.63)
|
36.73
(31.64)
|
24.93
(38.42)
|
13.01
(41.35)
|
27.53
(58.87)
|
| Title | Short Term Period: Peak Serum Concentration (Cmax) of Abatacept at Steady State in Participants With Rheumatoid Arthritis Receiving DMARDS |
|---|---|
| Description | Peak serum concentration (Cmax) of abatacept after weekly SC administration was determined between the SC dosing interval from Day 71 to 78. Abatacept in human serum was measured by enzyme-linked immunosorbent assay (ELISA). Lower limit of quantification (LLOQ) was 0.001, Upper limit of quantification (ULOQ) was 0.030. Cmax measured in micrograms per milliliter(µg/mL). Data are presented by treatment the participant actually received, not by what they were randomized to receive. |
| Time Frame | Day 71 to Day 78 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic (PK) analysis set included those participants treated with abatacept and having PK data available |
| Arm/Group Title | Group 1: 500 mg IV/75 mg SC (Body Weight < 60 kg) | Group 2: 500 mg IV/125 mg SC (Body Weight < 60 kg) | Group 3 : 750 mg IV/125 mg SC (Body Weight 60-100 kg) | Group 4: 1000mg IV/125 mg SC (Body Weight > 100 kg) | Group 5: 1000 mg IV/200 mg SC (Body Weight > 100 kg) |
|---|---|---|---|---|---|
| Arm/Group Description | Short term (ST) randomized 12 week period: Abatacept or Placebo as intravenous (IV) and subcutaneous (SC) administration: Abatacept 500 mg IV (Day 1)/Abatacept 75 mg SC (once weekly for 12 weeks); Long term extension (LTE) variable dosing period: 75 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period, IV placebo for participants randomized to abatacept in ST period). | Short term (ST) randomized 12 week period: Abatacept 500 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks) or Placebo. Long term extension (LTE) variable dosing period: 125 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period, IV placebo for participants randomized to abatacept in ST period). | Short term (ST) randomized 12 week period: Abatacept 750 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks) or Placebo. Long term extension (LTE) variable dosing period: 125 mg abatacept SC administered weekly following an IV loading dose on Day 85 ((IV abatacept for participants randomized to placebo in ST period, IV placebo for participants randomized to abatacept in ST period). Participants from Group 3 in ST period were rolled into Group 2 for LTE variable dosing period (125 mg SC abatacept). | Short term (ST) randomized 12 week period: Abatacept 1000 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks) or Placebo. Long term extension (LTE) variable dosing period: 125 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period, IV placebo for participants randomized to abatacept in ST period). Participants from Group 4 in ST period were rolled into Group 2 for LTE variable dosing period (125 mg SC abatacept). | Short term (ST) randomized 12 week period: Abatacept 1000 mg IV (Day 1)/Abatacept 200 mg SC (once weekly for 12 weeks) or Placebo. Long term extension (LTE) variable dosing period: 200 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period, IV placebo for participants randomized to abatacept in ST period). |
| Measure Participants | 7 | 4 | 26 | 5 | 5 |
| Geometric Mean (Geometric Coefficient of Variation) [µg/mL] |
26.3
(29.5)
|
34.9
(46.6)
|
31.9
(42.8)
|
14.7
(44.3)
|
41.7
(41.2)
|
| Title | Short Term Period: Area Under the Curve (AUC) in Time Interval of 7 Days [AUC(TAU)] of Abatacept in Participants With Rheumatoid Arthritis Receiving DMARDS |
|---|---|
| Description | The steady-state pharmacokinetic parameter AUC(TAU) of abatacept after weekly SC administration was determined between the SC dosing interval from Day 71 to 78 (TAU=7 days). Abatacept in human serum was measured by enzyme-linked immunosorbent assay (ELISA). Lower limit of quantification (LLOQ) was 0.001; Upper limit of quantification (ULOQ) was 0.030. AUC(TAU) measured in in micrograms*hours per milliliter (µg*h/mL). Data are presented by treatment the participant actually received, not by what they were randomized to receive. |
| Time Frame | Day 71 to Day 78 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic (PK) analysis set included those participants treated with abatacept and having PK data available. |
| Arm/Group Title | Group 1: 500 mg IV/75 mg SC (Body Weight < 60 kg) | Group 2: 500 mg IV/125 mg SC (Body Weight < 60 kg) | Group 3 : 750 mg IV/125 mg SC (Body Weight 60-100 kg) | Group 4: 1000mg IV/125 mg SC (Body Weight > 100 kg) | Group 5: 1000 mg IV/200 mg SC (Body Weight > 100 kg) |
|---|---|---|---|---|---|
| Arm/Group Description | Short term (ST) randomized 12 week period: Abatacept or Placebo as intravenous (IV) and subcutaneous (SC) administration: Abatacept 500 mg IV (Day 1)/Abatacept 75 mg SC (once weekly for 12 weeks); Long term extension (LTE) variable dosing period: 75 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period, IV placebo for participants randomized to abatacept in ST period). | Short term (ST) randomized 12 week period: Abatacept 500 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks) or Placebo. Long term extension (LTE) variable dosing period: 125 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period, IV placebo for participants randomized to abatacept in ST period). | Short term (ST) randomized 12 week period: Abatacept 750 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks) or Placebo. Long term extension (LTE) variable dosing period: 125 mg abatacept SC administered weekly following an IV loading dose on Day 85 ((IV abatacept for participants randomized to placebo in ST period, IV placebo for participants randomized to abatacept in ST period). Participants from Group 3 in ST period were rolled into Group 2 for LTE variable dosing period (125 mg SC abatacept). | Short term (ST) randomized 12 week period: Abatacept 1000 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks) or Placebo. Long term extension (LTE) variable dosing period: 125 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period, IV placebo for participants randomized to abatacept in ST period). Participants from Group 4 in ST period were rolled into Group 2 for LTE variable dosing period (125 mg SC abatacept). | Short term (ST) randomized 12 week period: Abatacept 1000 mg IV (Day 1)/Abatacept 200 mg SC (once weekly for 12 weeks) or Placebo. Long term extension (LTE) variable dosing period: 200 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period, IV placebo for participants randomized to abatacept in ST period). |
| Measure Participants | 7 | 3 | 24 | 4 | 5 |
| Geometric Mean (Geometric Coefficient of Variation) [µg*h/mL] |
4066
(22.2)
|
6699
(20.7)
|
4607
(38.6)
|
2555
(30.1)
|
5849
(40.5)
|
| Title | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Discontinuations Due to Adverse Events Reported During the Variable Dosing Phase of the Long Term Period (LTE) |
|---|---|
| Description | AEs during variable dose phase of LTE + 56 days post last dose in the variable dose phase or start of the fixed dose phase, which ever came first; includes deaths reported during the variable dose phase including those that occurred greater than 56 days after last dose. Medical Dictionary for Regulatory Activities (MedDRA) version: 15.1. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization (included hospitalizations for elective surgical procedures). Treatment-related=having certain, probable, possible, or missing relationship to study drug. Data presented by treatment the participant was randomized to and not what they actually received. |
| Time Frame | Day 85 to 56 days post last dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants included those that rolled over into the LTE, receiving variable SC dosing of abatacept in the Variable Dose Period. |
| Arm/Group Title | 75 mg SC Abatacept (Body Weight < 60 kg) | 125 mg SC Abatacept (Body Weight <60 to >100 kg) | 200 mg SC Abatacept (Body Weight > 100 kg) |
|---|---|---|---|
| Arm/Group Description | Long term extension (LTE) variable dosing period: 75 mg abatacept SC administered weekly following an IV loading dose (IV abatacept for participants randomized to placebo in ST period, loading dose 500 mg IV (Day 1)/Abatacept 75 mg SC (once weekly), or IV placebo for participants randomized to abatacept in ST period) on Day 85 (IV abatacept based on their weight at screening; < 60 kg received 500 mg abatacept IV, 60 - 100 kg received 750 mg abatacept IV, > 100 kg received 1000 mg abatacept IV for participants randomized to placebo in ST period)or, IV placebo for participants randomized to abatacept in ST period). At Day 365(1-year anniversary visit), subjects were reweighed for subsequent dosing to verify correct dosing in the variable-dose phase of the LTE period | Long term extension (LTE) variable dosing period: 125 mg abatacept SC administered weekly following an IV loading dose (IV abatacept for participants randomized to placebo in ST period, or IV placebo for participants randomized to abatacept in ST period) on Day 85 (IV abatacept based on their weight at screening; < 60 kg received 500 mg abatacept IV, 60 - 100 kg received 750 mg abatacept IV, > 100 kg received 1000 mg abatacept IV for participants randomized to placebo in ST period)or, IV placebo for participants randomized to abatacept in ST period). At Day 365(1-year anniversary visit), subjects were reweighed for subsequent dosing to verify correct dosing in the variable-dose phase of the LTE period. | 200 mg abatacept SC administered weekly following an IV loading dose on Day 85 (1000 mg IV abatacept for participants randomized to placebo in ST period, or IV placebo for participants randomized to abatacept in ST period). Participants reweighed at 1 year anniversary for subsequent dosing to verify correct dosing in the variable-dose phase of the LTE period |
| Measure Participants | 11 | 42 | 10 |
| Deaths |
0
0%
|
1
25%
|
0
0%
|
| Participants with SAEs |
2
28.6%
|
13
325%
|
4
13.8%
|
| Participants with drug related SAEs |
1
14.3%
|
2
50%
|
1
3.4%
|
| Participants discontinued due to SAEs |
0
0%
|
1
25%
|
1
3.4%
|
| Participants with AEs |
9
128.6%
|
38
950%
|
9
31%
|
| Participants with drug related AEs |
2
28.6%
|
20
500%
|
3
10.3%
|
| Participants discontinued due to AEs |
1
14.3%
|
2
50%
|
1
3.4%
|
| Title | Short Term Period: Summary of Adverse Events (AEs), Serious AEs, Deaths, and Discontinuations Due to AEs During 12 Weeks of Treatment With Either Abatacept or Placebo |
|---|---|
| Description | Number of Participants with Adverse events (AEs), Serious AEs, discontinuations due to AEs, or Deaths occurring while participant was on treatment from Day 1 (treatment) to Day 85 or early termination from the study. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization (also included hospitalizations for elective surgical procedures). Data are presented by treatment the participant actually received, not by what they were randomized to receive. |
| Time Frame | Day 1 to Day 85 (or early termination) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Group 1: 500 mg IV/75 mg SC (Body Weight < 60 kg) | Group 2: 500 mg IV/125 mg SC (Body Weight < 60 kg) | Group 3 : 750 mg IV/125 mg SC (Body Weight 60-100 kg) | Group 4: 1000mg IV/125 mg SC (Body Weight > 100 kg) | Group 5: 1000 mg IV/200 mg SC (Body Weight > 100 kg) | Placebo (by Body Weight Category) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects randomized to abatacept in group 1 received an intravenous (IV) loading dose of abatacept on Day 1 of 500 mg followed by 75 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). | Subjects randomized to abatacept in group 2 received an intravenous (IV) loading dose of abatacept on Day 1 of 500 mg followed by 125 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). | Subjects randomized to abatacept in group 3 received an intravenous (IV) loading dose of abatacept on Day 1 of 750 mg followed by 125 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). | Subjects randomized to abatacept in group 4 received an intravenous (IV) loading dose of abatacept on Day 1 of 1000 mg followed by 125 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). | Subjects randomized to abatacept in group 5 received an intravenous (IV) loading dose of abatacept on Day 1 of 1000 mg followed by 200 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). | Subjects randomized to placebo in the ST period received IV placebo followed by SC placebo (once weekly for 12 weeks). |
| Measure Participants | 7 | 4 | 29 | 6 | 5 | 17 |
| Deaths |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Participants with SAEs |
0
0%
|
1
25%
|
1
3.4%
|
0
0%
|
1
20%
|
0
0%
|
| Participants with AEs |
5
71.4%
|
3
75%
|
21
72.4%
|
6
100%
|
5
100%
|
11
64.7%
|
| Discontinued due to AEs |
0
0%
|
1
25%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
| Title | Short Term Period: Number of Participants With Pre-specified Adverse Events (AEs) of Special Interest After Administration of Abatacept or Placebo Over 12 Weeks |
|---|---|
| Description | AEs of special interest: infection and/or infestation; neoplasms (benign, malignant, unspecified; autoimmune disorder; infusional AEs (peri-infusional: AEs occurring during first 24 hours (hrs) after start of the IV loading dose; acute infusional: AEs occurring during the first hour after the start of the IV loading dose; injection site AEs: AEs occurring at the site of the SC injection. Data are presented by treatment the participant actually received, not by what they were randomized to receive. |
| Time Frame | Day 1 to Day 85 (or early termination) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All subjects treated were analyzed for safety. |
| Arm/Group Title | Group 1: 500 mg IV/75 mg SC (Body Weight < 60 kg) | Group 2: 500 mg IV/125 mg SC (Body Weight < 60 kg) | Group 3 : 750 mg IV/125 mg SC (Body Weight 60-100 kg) | Group 4: 1000mg IV/125 mg SC (Body Weight > 100 kg) | Group 5: 1000 mg IV/200 mg SC (Body Weight > 100 kg) | Placebo (by Body Weight Category) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects randomized to abatacept in group 1 received an IV loading dose of abatacept on Day 1 of 500 mg followed by abatacept 75 mg SC (once weekly for 12 weeks). | Subjects randomized to abatacept in group 2 received an IV loading dose of abatacept on Day 1 of 500 mg followed by abatacept 125 mg SC (once weekly for 12 weeks). | Subjects randomized to abatacept in group 3 received an IV loading dose of abatacept on Day 1 of 750 mg followed by abatacept 125 mg SC (once weekly for 12 weeks). | Subjects randomized to abatacept in group 4 received an IV loading dose of abatacept on Day 1 of 1000 mg followed by abatacept 125 mg SC (once weekly for 12 weeks). | Subjects randomized to abatacept in group 5 received an IV loading dose of abatacept on Day 1 of 1000 mg followed by abatacept 200 mg SC (once weekly for 12 weeks). | Subjects randomized to placebo in the ST period received IV placebo followed by SC placebo (once weekly for 12 weeks). |
| Measure Participants | 7 | 4 | 29 | 6 | 5 | 17 |
| Number with Infection/Infestation events |
3
42.9%
|
1
25%
|
9
31%
|
3
50%
|
1
20%
|
4
23.5%
|
| Number with malignant neoplasm events |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Number with autoimmune disorder events |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Number with acute infusional events |
0
0%
|
0
0%
|
2
6.9%
|
1
16.7%
|
0
0%
|
0
0%
|
| Number with peri-infusional events |
0
0%
|
0
0%
|
4
13.8%
|
3
50%
|
0
0%
|
0
0%
|
| General disorders and injection site events |
0
0%
|
1
25%
|
11
37.9%
|
3
50%
|
2
40%
|
1
5.9%
|
| Title | Short Term Period: Mean Percent Change From Baseline on Day 85 in Participants Positive for Serum Rheumatoid Factor During Abatacept or Placebo Administration |
|---|---|
| Description | Serum samples were obtained on Days 1, 8, 15, 29, 57 and day of discharge (Day 85 or earlier) for determination of presence of rheumatoid factor (RF). Baseline was defined as Day 1 to calculate percent change. Lower limit of quantitation (LLQ) was 5 Units/milliliter (U/mL). Values below LLQ were set to 2.5 U/mL. Data are presented by treatment the participant actually received, not by what they were randomized to receive. |
| Time Frame | Day 1 to Day 85 (or early termination) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis set included all available data from participants who received abatacept or placebo. For RF analysis in Group 1 Day 1/Day 85 number of participants = 7/7; Group 2 = 3/3; Group 3 = 29/29; Group 4 = 6/6; Group 5 = 5/5; Placebo = 17/15 participants. |
| Arm/Group Title | Group 1: 500 mg IV/75 mg SC (Body Weight < 60 kg) | Group 2: 500 mg IV/125 mg SC (Body Weight < 60 kg) | Group 3 : 750 mg IV/125 mg SC (Body Weight 60-100 kg) | Group 4: 1000mg IV/125 mg SC (Body Weight > 100 kg) | Group 5: 1000 mg IV/200 mg SC (Body Weight > 100 kg) | Placebo (by Body Weight Category) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Short term (ST) 12 week period: Abatacept as intravenous (IV) and subcutaneous (SC) administration: Abatacept 500 mg IV (Day 1)/Abatacept 75 mg SC (once weekly for 12 weeks). | Short term (ST) 12 week period: Abatacept 500 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks). | Short term (ST) randomized 12 week period: Abatacept 750 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks). | Short term (ST) 12 week period: Abatacept 1000 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks). | Short term (ST) 12 week period: Abatacept 1000 mg IV (Day 1)/Abatacept 200 mg SC (once weekly for 12 weeks). | Subjects randomized to placebo in the ST period received IV placebo followed by SC placebo (once weekly for 12 weeks). |
| Measure Participants | 7 | 3 | 29 | 6 | 5 | 15 |
| Mean (Standard Deviation) [percentage of change from baseline] |
-1.50
(43.50)
|
-8.89
(3.14)
|
-17.69
(26.61)
|
-16.29
(16.24)
|
-19.32
(15.21)
|
43.72
(154.47)
|
| Title | Short Term Period: Number of Participants With Laboratory Abnormalities in Hematology at Baseline (Day 1) to End of Period (Day 85) |
|---|---|
| Description | Blood samples were obtained: At screening, within 24 hours prior to study drug administration on Day 1, on Days 15, 29, 57 and at study discharge. Baseline (BL) defined as Day 1 prior to treatment. Common toxicity criteria (CTC), Version 3 used to assess parameters. lower limit of normal (LLN). ANC=absolute neutrophil count. White blood cells Grade (Gr) 1:<LLN to 3.0*10^9/L, Gr 2:<3.0 to 2.0*10^9/L, Gr 3:<2.0 to 1.0*10^9/L, Gr 4:<1.0*10^9/L. ANC Gr 1:<LLN to 1.5*10^9/L, Gr 2:<1.5 to 1.0*10^9/L, Gr 3:<1.0 to 0.5*10^9/L, Gr 4:<0.5*10^9/L. Lymphocytes Gr 1: <LLN to 3.0, Gr 2: 2.0 < 3.0, Gr 3: 1.0 to < 2.0, Gr 4; < 1.0. Platelet count Gr 1:LLN to 75.0*10^9/L, Gr 2:<75.0 to 50.0*10^9/L, Gr 3:<50.0 to 25.0*10^9/L, Gr 4:<25.0 to 10^9/L. Hemoglobin Gr 1:<LLN to 10.0 g/dL, Gr 2:<10.0 to 8.0 g/dL, Gr 3:<8.0 to 6.5 g/dL, Gr 4:<6.5 g/dL. Hematocrit (%): <0.75*pre-treatment. Data are presented by treatment the participant actually received, not by what they were randomized to receive. |
| Time Frame | Day 1 to Day 85 (or early termination) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants treated with either abatacept or placebo. Participant counted once in total for each arm but participant could have multiple AEs of different grade. Grade category is number of participants with that Grade of AE (Grades 1, 2, 3, 4) |
| Arm/Group Title | Group 1: 500 mg IV/75 mg SC (Body Weight < 60 kg) | Group 2: 500 mg IV/125 mg SC (Body Weight < 60 kg) | Group 3 : 750 mg IV/125 mg SC (Body Weight 60-100 kg) | Group 4: 1000mg IV/125 mg SC (Body Weight > 100 kg) | Group 5: 1000 mg IV/200 mg SC (Body Weight > 100 kg) | Placebo (by Body Weight Category) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects randomized to abatacept in group 1 received an intravenous (IV) loading dose of abatacept on Day 1 of 500 mg followed by 75 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). | Subjects randomized to abatacept in group 2 received an intravenous (IV) loading dose of abatacept on Day 1 of 500 mg followed by 125 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). | Subjects randomized to abatacept in group 3 received an intravenous (IV) loading dose of abatacept on Day 1 of 750 mg followed by 125 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). | Subjects randomized to abatacept in group 4 received an intravenous (IV) loading dose of abatacept on Day 1 of 1000 mg followed by 125 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). | Subjects randomized to abatacept in group 5 received an intravenous (IV) loading dose of abatacept on Day 1 of 1000 mg followed by 200 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). | Subjects randomized to placebo in the ST period received IV placebo followed by SC placebo (once weekly for 12 weeks). |
| Measure Participants | 7 | 4 | 29 | 6 | 5 | 17 |
| Baseline (Day 1 prior to treatment) Total |
4
57.1%
|
3
75%
|
15
51.7%
|
1
16.7%
|
2
40%
|
9
52.9%
|
| Grade 1 baseline |
4
57.1%
|
3
75%
|
13
44.8%
|
1
16.7%
|
2
40%
|
8
47.1%
|
| Grade 2 baseline |
0
0%
|
1
25%
|
2
6.9%
|
0
0%
|
0
0%
|
3
17.6%
|
| Grade 3 baseline |
0
0%
|
0
0%
|
1
3.4%
|
0
0%
|
0
0%
|
0
0%
|
| Grade 4 baseline |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Day 1 after treatment to Day 85 Total |
4
57.1%
|
4
100%
|
20
69%
|
1
16.7%
|
4
80%
|
13
76.5%
|
| Grade 1 on treatment |
4
57.1%
|
4
100%
|
17
58.6%
|
1
16.7%
|
3
60%
|
11
64.7%
|
| Grade 2 on treatment |
0
0%
|
1
25%
|
6
20.7%
|
0
0%
|
1
20%
|
3
17.6%
|
| Grade 3 on treatment |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
5.9%
|
| Grade 4 on treatment |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Short Term Period: Number of Participants With Laboratory Abnormalities in Serum Chemistry at Baseline and on Treatment up to Day 85 |
|---|---|
| Description | Screening, BL, Days 15, 29, 57, 85 or discharge. Upper limit of normal (ULN). CTC grade (Gr): Alanine transaminase Gr 1:>ULN to 2.5*ULN; Gr 2: >2.5 to 5.0*ULN; Gr 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. Aspartate aminotransferase Gr 1: >ULN to 2.5*ULN; Gr 2:>2.5 to 5.0*ULN; Gr 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. G-Glutamyl Transferase (U/L) Gr 1:>ULN to 2.5*ULN; Gr 2: >2.5 to 5.0*ULN; Gr 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. Alkaline phosphatase (U/L) Gr 1:>ULN to 2.5*ULN, Gr2:>2.5 to 5.0*ULN, Gr3:>5.0 to 20.0*ULN, Gr4: >20.0*ULN; creatinine (mg/dL) Gr 1: >ULN to 1.5*ULN; Gr 2: >1.5 to 3.0*ULN; Gr 3: >3.0 to 6.0*ULN; Gr 4: >10.0*ULN. Albumin (g/dL) Gr 1:<LLN to 3.0; Gr 2:<3.0 to 2.0; Gr 3: <2.0. Uric Acid (mg/dL)Gr 1: >1.0 x ULN to 10.0; Gr 4: >10.0. Sodium (mEq/L) Gr 1: >ULN to 150; Gr 2: >150 to 155; Gr 3: >155 to 160; Gr 4: > 160. Potassium (mEq/L) Gr 1: >ULN to 5.5; Gr 2: >5.5 to 6.0; Gr 3: >6.0 to 7.0; Gr 4: >7.0. Data presented by treatment participant actually received. |
| Time Frame | Day 1 to Day 85 (or early termination) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants treated with abatacept or placebo in the short term period. Participant is counted once in total but could have multiple AEs of different grade. Grade category is number of participants with that Grade of AE (Grades 1, 2, 3, 4) |
| Arm/Group Title | Group 1: 500 mg IV/75 mg SC (Body Weight < 60 kg) | Group 2: 500 mg IV/125 mg SC (Body Weight < 60 kg) | Group 3 : 750 mg IV/125 mg SC (Body Weight 60-100 kg) | Group 4: 1000mg IV/125 mg SC (Body Weight > 100 kg) | Group 5: 1000 mg IV/200 mg SC (Body Weight > 100 kg) | Placebo (by Body Weight Category) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects randomized to abatacept in group 1 received an intravenous (IV) loading dose of abatacept on Day 1 of 500 mg followed by 75 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). | Subjects randomized to abatacept in group 2 received an intravenous (IV) loading dose of abatacept on Day 1 of 500 mg followed by 125 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). | Subjects randomized to abatacept in group 3 received an intravenous (IV) loading dose of abatacept on Day 1 of 750 mg followed by 125 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). | Subjects randomized to abatacept in group 4 received an intravenous (IV) loading dose of abatacept on Day 1 of 1000 mg followed by 125 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). | Subjects randomized to abatacept in group 5 received an intravenous (IV) loading dose of abatacept on Day 1 of 1000 mg followed by 200 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). | Subjects randomized to placebo in the ST period received IV placebo followed by SC placebo (once weekly for 12 weeks). |
| Measure Participants | 7 | 4 | 29 | 6 | 5 | 17 |
| Baseline (Day 1 prior to treatment) Total |
2
28.6%
|
2
50%
|
6
20.7%
|
1
16.7%
|
4
80%
|
7
41.2%
|
| Grade 1 baseline |
2
28.6%
|
2
50%
|
5
17.2%
|
1
16.7%
|
4
80%
|
7
41.2%
|
| Grade 2 baseline |
0
0%
|
0
0%
|
1
3.4%
|
0
0%
|
0
0%
|
2
11.8%
|
| Grade 3 baseline |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Grade 4 baseline |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Day 1 (after treatment) to Day 85 Total |
5
71.4%
|
4
100%
|
18
62.1%
|
3
50%
|
4
80%
|
15
88.2%
|
| Grade 1 on treatment |
5
71.4%
|
0
0%
|
18
62.1%
|
3
50%
|
3
60%
|
15
88.2%
|
| Grade 2 on treatment |
1
14.3%
|
0
0%
|
4
13.8%
|
0
0%
|
0
0%
|
4
23.5%
|
| Grade 3 on treatment |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
20%
|
1
5.9%
|
| Grade 4 on treatment |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
20%
|
0
0%
|
| Title | Short Term Period: Mean Change From Baseline at Day 85 in Blood Pressure After SC Administration of Abatacept or Placebo in Participants With Rheumatoid Arthritis Receiving DMARDS |
|---|---|
| Description | Blood pressure (systolic and diastolic) was recorded while the participant was seated during the screening visit, at baseline on Day 1 (prior to administration of IV infusion), prior to administration of all SC injections, and at study discharge (Day 85 or 7 days after the last dose for subjects who terminated early). In addition, blood pressure was recorded at 30 and 60 minutes after the start of the IV infusion on Day 1, and 30 and 60 minutes after all SC injections. Blood pressure was measured in millimeters of mercury (mm Hg). Data are presented by treatment the participant actually received, not by what they were randomized to receive. |
| Time Frame | Day 1 to Day 85 (or early termination) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who were treated with abatacept or placebo and had vital signs taken were analyzed throughout the 12 weeks. At Day 85 N = 6, 3, 28,6, 5, 17 in groups 1, 2, 3, 4, 5, Placebo, respectively |
| Arm/Group Title | Group 1: 500 mg IV/75 mg SC (Body Weight < 60 kg) | Group 2: 500 mg IV/125 mg SC (Body Weight < 60 kg) | Group 3 : 750 mg IV/125 mg SC (Body Weight 60-100 kg) | Group 4: 1000mg IV/125 mg SC (Body Weight > 100 kg) | Group 5: 1000 mg IV/200 mg SC (Body Weight > 100 kg) | Placebo (by Body Weight Category) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects randomized to abatacept in group 1 received an intravenous (IV) loading dose of abatacept on Day 1 of 500 mg followed by 75 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). | Subjects randomized to abatacept in group 2 received an intravenous (IV) loading dose of abatacept on Day 1 of 500 mg followed by 125 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). | Subjects randomized to abatacept in group 3 received an intravenous (IV) loading dose of abatacept on Day 1 of 750 mg followed by 125 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). | Subjects randomized to abatacept in group 4 received an intravenous (IV) loading dose of abatacept on Day 1 of 1000 mg followed by 125 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). | Subjects randomized to abatacept in group 5 received an intravenous (IV) loading dose of abatacept on Day 1 of 1000 mg followed by 200 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). | Subjects randomized to placebo in the ST period received IV placebo followed by SC placebo (once weekly for 12 weeks). |
| Measure Participants | 7 | 4 | 29 | 6 | 5 | 17 |
| Change from baseline in Diastolic blood pressure |
-5.2
(10.0)
|
0.0
(13.1)
|
0.7
(7.5)
|
3.5
(11.2)
|
-5.4
(9.6)
|
1.8
(8.3)
|
| Change from baseline in Systolic blood pressure |
-4.0
(12.1)
|
-6.3
(6.8)
|
0.3
(17.8)
|
-0.8
(8.2)
|
-4.2
(10.5)
|
0.2
(12.1)
|
| Title | Short Term Period: Mean Change From Baseline at Day 85 in Pulse Rate After SC Administration of Abatacept or Placebo in Participants With Rheumatoid Arthritis Receiving DMARDS |
|---|---|
| Description | Pulse rate was taken while participant was seated. Pulse rate was recorded during the screening visit, at baseline on Day 1 (prior to administration of IV infusion), prior to administration of all SC injections, and at study discharge (Day 85 or 7 days after the last dose for subjects who terminated early). In addition, vital signs were recorded at 30 and 60 minutes after the start of the IV infusion on Day 1, and 30 and 60 minutes after all SC injections. Pulse rate measured in beats/min (bpm). Data are presented by treatment the participant actually received, not by what they were randomized to receive. |
| Time Frame | Day 1 to Day 85 (or early termination) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who were treated with abatacept or placebo and had vital signs taken were analyzed throughout the 12 weeks. At Day 85 N = 6, 3, 28, 6, 5, 17 in groups 1, 2, 3, 4, 5, Placebo, respectively |
| Arm/Group Title | Group 1: 500 mg IV/75 mg SC (Body Weight < 60 kg) | Group 2: 500 mg IV/125 mg SC (Body Weight < 60 kg) | Group 3 : 750 mg IV/125 mg SC (Body Weight 60-100 kg) | Group 4: 1000mg IV/125 mg SC (Body Weight > 100 kg) | Group 5: 1000 mg IV/200 mg SC (Body Weight > 100 kg) | Placebo (by Body Weight Category) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects randomized to abatacept in group 1 received an intravenous (IV) loading dose of abatacept on Day 1 of 500 mg followed by 75 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). | Subjects randomized to abatacept in group 2 received an intravenous (IV) loading dose of abatacept on Day 1 of 500 mg followed by 125 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). | Subjects randomized to abatacept in group 3 received an intravenous (IV) loading dose of abatacept on Day 1 of 750 mg followed by 125 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). | Subjects randomized to abatacept in group 4 received an intravenous (IV) loading dose of abatacept on Day 1 of 1000 mg followed by 125 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). | Subjects randomized to abatacept in group 5 received an intravenous (IV) loading dose of abatacept on Day 1 of 1000 mg followed by 200 mg subcutaneous (SC) abatacept (once weekly for 12 weeks). | Subjects randomized to placebo in the ST period received IV placebo followed by SC placebo (once weekly for 12 weeks). |
| Measure Participants | 7 | 4 | 29 | 6 | 5 | 17 |
| Mean (Standard Deviation) [bpm] |
-2.9
(10.0)
|
0.3
(11.1)
|
-0.6
(9.5)
|
3.5
(10.5)
|
-11.4
(9.0)
|
-1.0
(7.1)
|
| Title | Short Term Period: Mean Change From Screening to Day 85 in Electrocardiogram (QT, PR Intervals, QRS Width) After SC Administration of Abatacept or Placebo in Participants With Rheumatoid Arthritis Receiving DMARDS |
|---|---|
| Description | A 12-lead electrocardiogram (ECG) was recorded at screening and at discharge from the study (Day 85 or 7 days after the last dose of study drug for those subjects who terminated early). If there was no history of known cardiac events, an ECG was performed within 6 months of study entry, and documentation was on file, then the screening ECG was not repeated at screening. QT interval, PR interval and QRW Width were reported in milliseconds (msec). If no ECG issues were found in the 12 weeks of the Short Term Period, ECG was not repeated during LTE. Data are presented by treatment the participant actually received, not by what they were randomized to receive. |
| Time Frame | Screening to Day 85 (or early termination) |
Outcome Measure Data
| Analysis Population Description |
|---|
| A total of 68 participants were treated with abatacept or placebo: 66 had results at screening and 52 had results at Discharge (Day 85) for QT interval and QRS Width; 65 and 51 participants had PR interval results at Screening and Discharge (Day 85), respectively. |
| Arm/Group Title | All Treated Participants |
|---|---|
| Arm/Group Description | ECG change from screening after treatment were summarized for all participants treated with either abatacept or placebo in the Short Term Period. |
| Measure Participants | 66 |
| Change from Screening in QT interval (N=52) |
-1.47
(24.72)
|
| Change from Screening in PR interval (N=51) |
5.28
(21.10)
|
| Change from Screening in QRS Width (N=52) |
0.22
(11.03)
|
| Title | Number of Participants With Pre-specified AEs of Special Interest in the Variable Dosing Phase of Long Term Extension (LTE) |
|---|---|
| Description | LTE period with variable abatacept dosing starting on Day 85 and continuing until Day 533 when LTE fixed dosing started. AEs of special interest: infection and/or infestation; neoplasms (malignant); pre-specified autoimmune disorder; infusional AEs (peri-infusional: pre-specified AEs occurring during first 24 hours (hrs) after start of the IV loading dose; acute infusional: pre-specified AEs occurring during the first hour after the start of the IV loading dose; systemic injection site reactions (SIR): pre-specified AEs for SIR; local injection site reaction: pre-specified AEs for local site reaction. Data are presented by treatment the participant was randomized to and not what they actually received. |
| Time Frame | Day 85 to Day 533 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All 63 participants who completed the ST period enrolled into the LTE variable dosing period and were analyzed. |
| Arm/Group Title | 75 mg SC Abatacept | 125 mg SC Abatacept | 200 mg SC Abatacept |
|---|---|---|---|
| Arm/Group Description | variable dosing period: 75 mg abatacept SC administered weekly following an IV loading dose (IV abatacept for participants randomized to placebo in ST period, or IV placebo for participants randomized to abatacept in ST period); body weight <60kg. At Day 365(1-year anniversary visit), subjects were reweighed for subsequent dosing to verify correct dosing in the variable-dose phase of the LTE period | 125 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period, loading dose as described in group 1 description, or IV placebo for participants randomized to abatacept in ST period). Body weight <60 to >100 kg. Participants reweighed at 1 year anniversary for subsequent dosing to verify correct dosing in the variable-dose phase of the LTE period. | 200 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period, or IV placebo for participants randomized to abatacept in ST period); body weight >100kg. Participants reweighed at 1 year anniversary for subsequent dosing to verify correct dosing in the variable-dose phase of the LTE period |
| Measure Participants | 11 | 42 | 10 |
| Number with Serious Infection/Infestation |
1
14.3%
|
1
25%
|
2
6.9%
|
| Number with Malignant Neoplasms |
1
14.3%
|
5
125%
|
1
3.4%
|
| Number with Autoimmune Disorder |
0
0%
|
1
25%
|
0
0%
|
| Number with Acute Infusional Event |
0
0%
|
0
0%
|
0
0%
|
| Number with Serious Systemic injection Reaction |
0
0%
|
0
0%
|
0
0%
|
| Number with Local Injection Site Reaction |
0
0%
|
4
100%
|
0
0%
|
| Title | Short Term Period: Mean Change From Screening at Day 85 in ECG (Heart Rate) After SC Administration of Abatacept or Placebo in Participants With Rheumatoid Arthritis Receiving DMARDS |
|---|---|
| Description | A 12-lead electrocardiogram (ECG) was recorded at screening and at discharge from the study (Day 85 or 7 days after the last dose of study drug for those subjects who terminated early). If there was no history of known cardiac events, an ECG was performed within 6 months of study entry, and documentation was on file, then the screening ECG was not repeated at screening. Heart Rate was reported in beats per minute (bpm). In no ECG issues were found in the 12 weeks of the Short Term Period, ECG was not repeated during LTE. Data are presented by treatment the participant actually received, not by what they were randomized to receive. |
| Time Frame | Screening to Day 85 (or early termination) |
Outcome Measure Data
| Analysis Population Description |
|---|
| A total of 68 participants were treated with abatacept or placebo: 65 had results at screening and 53 had results at Discharge (Day 85) for Heart Rate. |
| Arm/Group Title | All Treated Participants |
|---|---|
| Arm/Group Description | ECG Heart Rate change from screening after treatment were summarized for all participants treated with either abatacept or placebo in the Short Term Period |
| Measure Participants | 53 |
| Mean (Standard Deviation) [bpm] |
0.51
(8.43)
|
| Title | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Discontinuations Due to Adverse Events Summarized Over the Entire Long Term Extension (LTE) Period (Both Variable and Fixed Dosing) |
|---|---|
| Description | On Day 85 participants rolled over into the LTE with variable dose phase first and at Day 533, a fixed dose phase of 125 mg abatacept SC weekly, irrespective of body weight. This summary includes AEs reported during entire LTE treatment plus 56 days post last dose; includes all deaths reported during the LTE including those that occurred greater than 56 days after last dose. MedDRA version: 15.1. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization (also included hospitalizations for elective surgical procedures). Treatment-related=having certain, probable, possible, or missing relationship to study drug. |
| Time Frame | Day 533 to 56 Days Post last dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| total number of participants in the Long Term Extension Period. |
| Arm/Group Title | SC Abatacept |
|---|---|
| Arm/Group Description | Overall summary of all participants in the LTE. LTE Period consisted of a variable dose (75 mg, 125 mg, 200 mg abatacept) phase first and at Day 533, a fixed dose phase of 125 mg abatacept SC weekly, irrespective of body weight. |
| Measure Participants | 63 |
| Deaths |
6
85.7%
|
| Participants with SAEs |
35
500%
|
| Participants with Drug Related SAEs |
7
100%
|
| Participants Discontinued due to SAEs |
3
42.9%
|
| Participants with AEs |
61
871.4%
|
| Participants with Drug Related AEs |
34
485.7%
|
| Participants Discontinued due to AEs |
5
71.4%
|
| Title | Overall Study ST and LTE Periods: Number of Participants With Anti-abatacept Antibodies and/or Anti-cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Antibodies |
|---|---|
| Description | Assessment of positive antibody response based upon analysis using a validated enzyme-linked immunosorbent assay (ELISA) with a cut-off value. CTLA4 is a protein receptor that downregulates the immune system. Short Term (ST) period was initial 12 Weeks of the study. Overall LTE includes both the variable and fixed abatacept dosing periods and was from the end of the ST period (Day 85) up to 168 days post last dose (treatment in LTE ranged from 4.4 to 74.2 months. Data in the ST period are summarized by the treatment the participants actually received, while the LT period data are summarized by treatment the participant was randomized to receive. |
| Time Frame | ST: Day 1 to Day 85; LTE: Day 85 to 168 days post last dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| In the ST period, only subjects treated with abatacept (51) were evaluated for antibodies. In LTE, 61 participants were analyzed for anti-abatacept antibodies, and 62 participants were analyzed for CTLA4-T antibodies. Participants were analyzed during treatment and post-treatment (28, 56, 85, and 168 days post-treatment). |
| Arm/Group Title | Group 1: 500 mg IV/75 mg SC (Body Weight < 60 kg) | Group 2: 500 mg IV/125 mg SC (Body Weight < 60 kg) | Group 3 : 750 mg IV/125 mg SC (Body Weight 60-100 kg) | Group 4: 1000mg IV/125 mg SC (Body Weight > 100 kg) | Group 5: 1000 mg IV/200 mg SC (Body Weight > 100 kg) | LTE (Variable and Fixed Dosing Abatacept) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Short term (ST) 12 week period: Abatacept as intravenous (IV) and subcutaneous (SC) administration: Abatacept 500 mg IV (Day 1)/Abatacept 75 mg SC (once weekly for 12 weeks) | Short term (ST) 12 week period: Abatacept 500 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks). | Short term (ST) 12 week period: Abatacept 750 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks). | Short term (ST) randomized 12 week period: Abatacept 1000 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks). | Short term (ST) 12 week period: Abatacept 1000 mg IV (Day 1)/Abatacept 200 mg SC (once weekly for 12 weeks). | Long term extension (LTE) consisted of 2 periods: variable dosing of abatacept combined with DMARDS and fixed dosing abatacept combined with DMARDS. Participants were weighed prior to starting LTE (variable dosing) and dosing was assigned per body weight category. Variable dosing period required an IV loading dose prior to starting SC dosing (if participant had been randomized to placebo in the short term period). Variable dosing: 500 mg IV/75 mg SC and 500 mg IV/125 mg SC in participants less than (<)60 kg body weight; 750 mg IV/125 mg SC in participants between 60 and 100 kg body weight; 1000 mg IV/125 mg SC and 1000 mg IV/200 mg SC in participants greater than (>) 100 kg body weight. Participants were rolled over into a fixed SC dose of 125 mg per week in the fixed dosing period prior to their Year 2 anniversary visit for the study (as early as Day 533). |
| Measure Participants | 7 | 4 | 29 | 6 | 5 | 62 |
| Number with anti-abatacept antibodies |
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
11
64.7%
|
| Number with anti-CTLA4 antibodies |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
5.9%
|
Adverse Events
| Time Frame | Day 1 of short term study up to 71 months in the long term study. | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | AEs and SAEs are summarized by the treatment arm to which the participants were randomized. | |||||||||||||
| Arm/Group Title | Abatacept 1000mg IV/125mg SC | Abatacept 1000mg IV/200mg SC | Abatacept 500mg IV/125mg SC | Abatacept 500mg IV/75mg SC | Abatacept 750mg IV/125mg SC | Abatacept (LT) 125 mg SC | Placebo (ST) | |||||||
| Arm/Group Description | Short term (ST) randomized 12 week period: Abatacept 1000 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks) or Placebo. Long term extension (LTE) variable dosing period: 125 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period, loading dose as described in group 1 description, or IV placebo for participants randomized to abatacept in ST period). Participants reweighed at 1 year anniversary for subsequent dosing to verify correct dosing in the variable-dose phase of the LTE period. | Short term (ST) randomized 12 week period: Abatacept 1000 mg IV (Day 1)/Abatacept 200 mg SC (once weekly for 12 weeks) or Placebo. Long term extension (LTE) variable dosing period: 200 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period, loading dose based on weight as described in Group 1 description, or IV placebo for participants randomized to abatacept in ST period). Participants reweighed at 1 year anniversary for subsequent dosing to verify correct dosing in the variable-dose phase of the LTE period. | Short term (ST) randomized 12 week period: Abatacept 500 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks) or Placebo. Long term extension (LTE) variable dosing period: 125 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period; loading dose described in Group 1 description, or IV placebo for participants randomized to abatacept in ST period). Participants reweighed at 1 year anniversary for subsequent dosing to verify correct dosing in the variable-dose phase of the LTE period. | Short term (ST) randomized 12 week period: Abatacept or Placebo as intravenous (IV) and subcutaneous (SC) administration: Abatacept 500 mg IV (Day 1)/Abatacept 75 mg SC (once weekly for 12 weeks); Long term extension (LTE) variable dosing period: 75 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept based on their weight at screening; < 60 kg received 500 mg abatacept IV, 60 - 100 kg received 750 mg abatacept IV, > 100 kg received 1000 mg abatacept IV for participants randomized to placebo in ST period)or, IV placebo for participants randomized to abatacept in ST period). At Day 365(1-year anniversary visit), subjects were reweighed for subsequent dosing to verify correct dosing in the variable-dose phase of the LTE period. | Short term (ST) randomized 12 week period: Abatacept 750 mg IV (Day 1)/Abatacept 125 mg SC (once weekly for 12 weeks) or Placebo. Long term extension (LTE) variable dosing period: 125 mg abatacept SC administered weekly following an IV loading dose on Day 85 (IV abatacept for participants randomized to placebo in ST period, loading dose described in Group 1 description, or IV placebo for participants randomized to abatacept in ST period). Participants reweighed at 1 year anniversary for subsequent dosing to verify correct dosing in the variable-dose phase of the LTE period. | Participants who completed the long term extension (LTE)period and received variable doses of subcutaneous (SC) abatacept (as described in Groups 1 - 5) were rolled over into the LTE with fixed dose: SC abatacept 125 milligram (mg) in pre-filled syringes, administered Weekly. | Short term (ST) randomized 12 week period: Placebo IV(Day 1)/Placebo SC (once weekly for 12 weeks). Long term extension (LTE) variable dosing period: all placebo participants rolled over to a variable dose of abatacept SC (75, 125, 200 mg) administered weekly following an IV loading dose of abatacept on Day 85. Participants reweighed at 1 year anniversary for subsequent dosing to verify correct dosing in the variable-dose phase of the LTE period. | |||||||
All Cause Mortality |
||||||||||||||
| Abatacept 1000mg IV/125mg SC | Abatacept 1000mg IV/200mg SC | Abatacept 500mg IV/125mg SC | Abatacept 500mg IV/75mg SC | Abatacept 750mg IV/125mg SC | Abatacept (LT) 125 mg SC | Placebo (ST) | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | 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) | / (NaN) | / (NaN) | |||||||
Serious Adverse Events |
||||||||||||||
| Abatacept 1000mg IV/125mg SC | Abatacept 1000mg IV/200mg SC | Abatacept 500mg IV/125mg SC | Abatacept 500mg IV/75mg SC | Abatacept 750mg IV/125mg SC | Abatacept (LT) 125 mg SC | Placebo (ST) | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/6 (16.7%) | 0/5 (0%) | 1/5 (20%) | 0/6 (0%) | 1/28 (3.6%) | 35/63 (55.6%) | 0/18 (0%) | |||||||
| Blood and lymphatic system disorders | ||||||||||||||
| Anaemia | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 2/63 (3.2%) | 0/18 (0%) | |||||||
| Cardiac disorders | ||||||||||||||
| Atrial flutter | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Cardiac failure congestive | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 2/63 (3.2%) | 0/18 (0%) | |||||||
| Atrial fibrillation | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 2/63 (3.2%) | 0/18 (0%) | |||||||
| Myocardial infarction | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 2/63 (3.2%) | 0/18 (0%) | |||||||
| Sick sinus syndrome | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Diastolic dysfunction | 1/6 (16.7%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 0/63 (0%) | 0/18 (0%) | |||||||
| Ear and labyrinth disorders | ||||||||||||||
| Vertigo | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Gastrointestinal disorders | ||||||||||||||
| Gastritis | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Abdominal pain | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Erosive oesophagitis | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Gastrointestinal haemorrhage | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Peptic ulcer haemorrhage | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| General disorders | ||||||||||||||
| Chest discomfort | 1/6 (16.7%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 0/63 (0%) | 0/18 (0%) | |||||||
| Adverse drug reaction | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Death | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Injection site reaction | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Impaired healing | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Chest pain | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Infections and infestations | ||||||||||||||
| Lobar pneumonia | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Pneumonia | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 4/63 (6.3%) | 0/18 (0%) | |||||||
| Wound infection | 0/6 (0%) | 0/5 (0%) | 1/5 (20%) | 0/6 (0%) | 0/28 (0%) | 0/63 (0%) | 0/18 (0%) | |||||||
| Meningitis | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| H1N1 influenza | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Staphylococcal infection | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Urinary tract infection | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 3/63 (4.8%) | 0/18 (0%) | |||||||
| Gastroenteritis | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Injury, poisoning and procedural complications | ||||||||||||||
| Overdose | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 1/28 (3.6%) | 0/63 (0%) | 0/18 (0%) | |||||||
| Hip fracture | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Spinal fracture | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Metabolism and nutrition disorders | ||||||||||||||
| Diabetes mellitus inadequate control | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||
| Arthralgia | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Rotator cuff syndrome | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Spinal disorder | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Lumbar spinal stenosis | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Joint contracture | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Rheumatoid arthritis | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 4/63 (6.3%) | 0/18 (0%) | |||||||
| Osteoarthritis | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 5/63 (7.9%) | 0/18 (0%) | |||||||
| Intervertebral disc disorder | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||
| Basal cell carcinoma | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 7/63 (11.1%) | 0/18 (0%) | |||||||
| Colon cancer | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Lip neoplasm malignant stage unspecified | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Malignant melanoma | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 2/63 (3.2%) | 0/18 (0%) | |||||||
| Squamous cell carcinoma of skin | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 2/63 (3.2%) | 0/18 (0%) | |||||||
| Squamous cell carcinoma | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 4/63 (6.3%) | 0/18 (0%) | |||||||
| Nervous system disorders | ||||||||||||||
| Presyncope | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Transient ischaemic attack | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Psychiatric disorders | ||||||||||||||
| Mental status changes | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Renal and urinary disorders | ||||||||||||||
| Renal failure acute | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||
| Emphysema | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Asthma | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 2/63 (3.2%) | 0/18 (0%) | |||||||
| Dyspnoea | 1/6 (16.7%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Sleep apnoea syndrome | 1/6 (16.7%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 0/63 (0%) | 0/18 (0%) | |||||||
| Chronic obstructive pulmonary disease | 1/6 (16.7%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Vascular disorders | ||||||||||||||
| Iliac artery occlusion | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||
| Abatacept 1000mg IV/125mg SC | Abatacept 1000mg IV/200mg SC | Abatacept 500mg IV/125mg SC | Abatacept 500mg IV/75mg SC | Abatacept 750mg IV/125mg SC | Abatacept (LT) 125 mg SC | Placebo (ST) | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/6 (100%) | 5/5 (100%) | 2/5 (40%) | 5/6 (83.3%) | 18/28 (64.3%) | 58/63 (92.1%) | 12/18 (66.7%) | |||||||
| Blood and lymphatic system disorders | ||||||||||||||
| Anaemia | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 8/63 (12.7%) | 0/18 (0%) | |||||||
| Lymphadenopathy | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 0/63 (0%) | 1/18 (5.6%) | |||||||
| Ear and labyrinth disorders | ||||||||||||||
| Ear pain | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 4/63 (6.3%) | 0/18 (0%) | |||||||
| Eye disorders | ||||||||||||||
| Cataract | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 1/28 (3.6%) | 8/63 (12.7%) | 0/18 (0%) | |||||||
| Vision blurred | 1/6 (16.7%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 1/28 (3.6%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Glaucoma | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/28 (0%) | 2/63 (3.2%) | 0/18 (0%) | |||||||
| Gastrointestinal disorders | ||||||||||||||
| Gastritis | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 5/63 (7.9%) | 0/18 (0%) | |||||||
| Gastrooesophageal reflux disease | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 9/63 (14.3%) | 0/18 (0%) | |||||||
| Vomiting | 1/6 (16.7%) | 1/5 (20%) | 0/5 (0%) | 0/6 (0%) | 2/28 (7.1%) | 4/63 (6.3%) | 0/18 (0%) | |||||||
| Food poisoning | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/28 (0%) | 0/63 (0%) | 0/18 (0%) | |||||||
| Nausea | 1/6 (16.7%) | 1/5 (20%) | 0/5 (0%) | 0/6 (0%) | 2/28 (7.1%) | 10/63 (15.9%) | 1/18 (5.6%) | |||||||
| Diarrhoea | 0/6 (0%) | 1/5 (20%) | 0/5 (0%) | 0/6 (0%) | 2/28 (7.1%) | 8/63 (12.7%) | 2/18 (11.1%) | |||||||
| Abdominal discomfort | 1/6 (16.7%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 1/28 (3.6%) | 3/63 (4.8%) | 1/18 (5.6%) | |||||||
| Irritable bowel syndrome | 0/6 (0%) | 1/5 (20%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 0/63 (0%) | 0/18 (0%) | |||||||
| General disorders | ||||||||||||||
| Chest discomfort | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 4/63 (6.3%) | 0/18 (0%) | |||||||
| Chills | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 2/28 (7.1%) | 0/63 (0%) | 0/18 (0%) | |||||||
| Injection site reaction | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 3/28 (10.7%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Injection site haematoma | 0/6 (0%) | 1/5 (20%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Injection site warmth | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 2/28 (7.1%) | 0/63 (0%) | 0/18 (0%) | |||||||
| Oedema peripheral | 2/6 (33.3%) | 1/5 (20%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 12/63 (19%) | 0/18 (0%) | |||||||
| Asthenia | 0/6 (0%) | 1/5 (20%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 3/63 (4.8%) | 0/18 (0%) | |||||||
| Fatigue | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 1/28 (3.6%) | 7/63 (11.1%) | 0/18 (0%) | |||||||
| Injection site erythema | 0/6 (0%) | 1/5 (20%) | 0/5 (0%) | 0/6 (0%) | 1/28 (3.6%) | 0/63 (0%) | 1/18 (5.6%) | |||||||
| Injection site pain | 0/6 (0%) | 0/5 (0%) | 1/5 (20%) | 0/6 (0%) | 3/28 (10.7%) | 1/63 (1.6%) | 1/18 (5.6%) | |||||||
| Injection site swelling | 1/6 (16.7%) | 1/5 (20%) | 0/5 (0%) | 0/6 (0%) | 1/28 (3.6%) | 0/63 (0%) | 0/18 (0%) | |||||||
| Pyrexia | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 2/28 (7.1%) | 5/63 (7.9%) | 0/18 (0%) | |||||||
| Infections and infestations | ||||||||||||||
| Bronchitis | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/28 (0%) | 13/63 (20.6%) | 1/18 (5.6%) | |||||||
| Gastroenteritis viral | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 1/6 (16.7%) | 2/28 (7.1%) | 3/63 (4.8%) | 0/18 (0%) | |||||||
| Sinusitis | 1/6 (16.7%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 14/63 (22.2%) | 0/18 (0%) | |||||||
| Pneumonia | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 4/63 (6.3%) | 0/18 (0%) | |||||||
| Tooth abscess | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 1/6 (16.7%) | 1/28 (3.6%) | 5/63 (7.9%) | 1/18 (5.6%) | |||||||
| Viral upper respiratory tract infection | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 1/18 (5.6%) | |||||||
| Influenza | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 5/63 (7.9%) | 0/18 (0%) | |||||||
| Otitis externa | 0/6 (0%) | 1/5 (20%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 0/63 (0%) | 0/18 (0%) | |||||||
| Upper respiratory tract infection | 1/6 (16.7%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 3/28 (10.7%) | 22/63 (34.9%) | 2/18 (11.1%) | |||||||
| Urinary tract infection | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 1/6 (16.7%) | 4/28 (14.3%) | 13/63 (20.6%) | 0/18 (0%) | |||||||
| Viral infection | 1/6 (16.7%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Nasopharyngitis | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 1/28 (3.6%) | 8/63 (12.7%) | 0/18 (0%) | |||||||
| Injury, poisoning and procedural complications | ||||||||||||||
| Rib fracture | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 1/6 (16.7%) | 1/28 (3.6%) | 3/63 (4.8%) | 0/18 (0%) | |||||||
| Arthropod bite | 1/6 (16.7%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Ligament sprain | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 5/63 (7.9%) | 0/18 (0%) | |||||||
| Procedural pain | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Contusion | 0/6 (0%) | 1/5 (20%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 4/63 (6.3%) | 0/18 (0%) | |||||||
| Foot fracture | 0/6 (0%) | 1/5 (20%) | 0/5 (0%) | 0/6 (0%) | 1/28 (3.6%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Fall | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 2/6 (33.3%) | 0/28 (0%) | 7/63 (11.1%) | 0/18 (0%) | |||||||
| Nail injury | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/28 (0%) | 0/63 (0%) | 0/18 (0%) | |||||||
| Laceration | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 7/63 (11.1%) | 1/18 (5.6%) | |||||||
| Tendon rupture | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 4/63 (6.3%) | 0/18 (0%) | |||||||
| Investigations | ||||||||||||||
| Intraocular pressure increased | 0/6 (0%) | 1/5 (20%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Transaminases increased | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Urine analysis abnormal | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/28 (0%) | 2/63 (3.2%) | 0/18 (0%) | |||||||
| Hepatic enzyme increased | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 0/63 (0%) | 1/18 (5.6%) | |||||||
| Weight decreased | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 0/63 (0%) | 1/18 (5.6%) | |||||||
| Liver function test abnormal | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 4/63 (6.3%) | 0/18 (0%) | |||||||
| Metabolism and nutrition disorders | ||||||||||||||
| Dehydration | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 0/63 (0%) | 1/18 (5.6%) | |||||||
| Hypokalaemia | 1/6 (16.7%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 1/28 (3.6%) | 5/63 (7.9%) | 0/18 (0%) | |||||||
| Fluid retention | 1/6 (16.7%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Hypercholesterolaemia | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 1/28 (3.6%) | 4/63 (6.3%) | 0/18 (0%) | |||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||
| Pain in extremity | 1/6 (16.7%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 1/28 (3.6%) | 7/63 (11.1%) | 0/18 (0%) | |||||||
| Neck pain | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 1/28 (3.6%) | 4/63 (6.3%) | 0/18 (0%) | |||||||
| Back pain | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 1/6 (16.7%) | 3/28 (10.7%) | 14/63 (22.2%) | 3/18 (16.7%) | |||||||
| Musculoskeletal pain | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 1/6 (16.7%) | 1/28 (3.6%) | 7/63 (11.1%) | 0/18 (0%) | |||||||
| Osteopenia | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 4/63 (6.3%) | 0/18 (0%) | |||||||
| Osteoarthritis | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 4/63 (6.3%) | 0/18 (0%) | |||||||
| Bursitis | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/28 (0%) | 4/63 (6.3%) | 0/18 (0%) | |||||||
| Muscle spasms | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 1/28 (3.6%) | 3/63 (4.8%) | 1/18 (5.6%) | |||||||
| Nervous system disorders | ||||||||||||||
| Dizziness | 1/6 (16.7%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 1/28 (3.6%) | 5/63 (7.9%) | 3/18 (16.7%) | |||||||
| Headache | 3/6 (50%) | 2/5 (40%) | 0/5 (0%) | 0/6 (0%) | 1/28 (3.6%) | 8/63 (12.7%) | 3/18 (16.7%) | |||||||
| Neuropathy peripheral | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Sciatica | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 1/28 (3.6%) | 4/63 (6.3%) | 0/18 (0%) | |||||||
| Carpal tunnel syndrome | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 1/18 (5.6%) | |||||||
| Sinus headache | 1/6 (16.7%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 0/63 (0%) | 0/18 (0%) | |||||||
| Psychiatric disorders | ||||||||||||||
| Anxiety | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 2/28 (7.1%) | 2/63 (3.2%) | 0/18 (0%) | |||||||
| Depression | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 1/28 (3.6%) | 5/63 (7.9%) | 0/18 (0%) | |||||||
| Insomnia | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 2/63 (3.2%) | 1/18 (5.6%) | |||||||
| Renal and urinary disorders | ||||||||||||||
| Pollakiuria | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||
| Rhinitis allergic | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 1/18 (5.6%) | |||||||
| Sinus congestion | 1/6 (16.7%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 4/63 (6.3%) | 0/18 (0%) | |||||||
| Cough | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 1/6 (16.7%) | 2/28 (7.1%) | 13/63 (20.6%) | 0/18 (0%) | |||||||
| Pulmonary hypertension | 1/6 (16.7%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Asthma | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 6/63 (9.5%) | 0/18 (0%) | |||||||
| Productive cough | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 1/28 (3.6%) | 6/63 (9.5%) | 0/18 (0%) | |||||||
| Dyspnoea | 1/6 (16.7%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 11/63 (17.5%) | 0/18 (0%) | |||||||
| Rhinorrhoea | 0/6 (0%) | 1/5 (20%) | 0/5 (0%) | 1/6 (16.7%) | 1/28 (3.6%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Respiratory tract congestion | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 4/63 (6.3%) | 0/18 (0%) | |||||||
| Oropharyngeal pain | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 2/63 (3.2%) | 1/18 (5.6%) | |||||||
| Pleural effusion | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 4/63 (6.3%) | 0/18 (0%) | |||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||
| Pruritus | 0/6 (0%) | 1/5 (20%) | 0/5 (0%) | 0/6 (0%) | 2/28 (7.1%) | 3/63 (4.8%) | 0/18 (0%) | |||||||
| Rash | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 1/28 (3.6%) | 8/63 (12.7%) | 1/18 (5.6%) | |||||||
| Actinic keratosis | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 5/63 (7.9%) | 1/18 (5.6%) | |||||||
| Dermatitis | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 4/63 (6.3%) | 0/18 (0%) | |||||||
| Scab | 1/6 (16.7%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 0/63 (0%) | 0/18 (0%) | |||||||
| Urticaria | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 2/28 (7.1%) | 1/63 (1.6%) | 0/18 (0%) | |||||||
| Vascular disorders | ||||||||||||||
| Flushing | 1/6 (16.7%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 1/28 (3.6%) | 2/63 (3.2%) | 1/18 (5.6%) | |||||||
| Haemorrhage | 0/6 (0%) | 0/5 (0%) | 1/5 (20%) | 0/6 (0%) | 0/28 (0%) | 0/63 (0%) | 0/18 (0%) | |||||||
| Hypotension | 0/6 (0%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 1/28 (3.6%) | 1/63 (1.6%) | 1/18 (5.6%) | |||||||
| Hypertension | 1/6 (16.7%) | 0/5 (0%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 6/63 (9.5%) | 0/18 (0%) | |||||||
| Phlebitis superficial | 0/6 (0%) | 1/5 (20%) | 0/5 (0%) | 0/6 (0%) | 0/28 (0%) | 0/63 (0%) | 0/18 (0%) | |||||||
Limitations/Caveats
Error resulted in 4 participants being treated with study drug they were not randomized to receive. ST data were summarized by study drug participants actually received while LT data were summarized by what participants were randomized to receive.
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 | Bristol-Myers Squibb Study Director |
|---|---|
| Organization | Bristol-Myers Squibb |
| Phone | |
| Clinical.Trials@bms.com |
Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00254293
Other Study ID Numbers:
- IM101-063
First Posted:
Nov 16, 2005
Last Update Posted:
Apr 8, 2014
Last Verified:
Mar 1, 2014