Optimization of NULOJIX® Usage Towards Minimizing CNI Exposure in Simultaneous Pancreas and Kidney Transplantation

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Terminated
• CT.gov ID: NCT01790594
• Collaborator: Clinical Trials in Organ Transplantation (Other), Rho Federal Systems Division, Inc. (Industry), Bristol-Myers Squibb (Industry)
• Enrollment: 46
• Locations: 5
• Arms: 2
• Duration (Months): 42
• Patients Per Site: 9.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to find out if the drug NULOJIX® (belatacept) will minimize the amount of other anti-rejection medications necessary and thereby reduce the long-term side effects caused by the other medications. The researchers also want to learn more about the safety of this treatment and long term health of transplanted pancreases and kidneys.

Condition or Disease	Intervention/Treatment	Phase
Simultaneous Kidney and Pancreas Transplantation	Biological: Belatacept; Drug: methylprednisolone; Biological: Anti-thymocyte Globulin (Rabbit); Drug: Tacrolimus; Drug: Mycophenolate mofetil	Phase 2

Detailed Description

Transplant recipients have to take anti-rejection medications to prevent their immune systems (the body's natural defense system against illness) from rejecting their new organs. Most patients who receive a transplanted organ must take these anti-rejection medications for the rest of their lives, or for as long as the transplanted organ continues to work. Taking standard anti-rejection medications for a long time can cause serious side effects, including pancreas and kidney damage. There would be a benefit to finding new anti-rejection medications that work just as well, but could lessen the amount of anti-rejection medications that are taken long term.

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Optimization of NULOJIX® (Belatacept) Usage as a Means of Minimizing CNI Exposure in Simultaneous Pancreas and Kidney Transplantation (CTOT-15)
• Study Start Date: Feb 1, 2013
• Actual Primary Completion Date: Aug 1, 2016
• Actual Study Completion Date: Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Immunosuppression without Belatacept Induction: 5 day course of methylprednisolone or equivalent; Induction: Anti-thymocyte Globulin (Rabbit); Maintenance Immunosuppression: Tacrolimus (or generic). The site investigator will identify a starting tacrolimus dose at his or her discretion, in order to achieve the target trough levels, no later than 5 days post-transplantation. Tacrolimus dosing will be initiated on the day of surgery or post-operative day 1 depending upon when during the day the surgery is completed, then adjusted to target trough levels of 8-12 ng/ml during the first 24 weeks post-transplant, then adjusted to target trough levels of 5-8 ng/ml thereafter. Maintenance Immunosuppression: Mycophenolate mofetil (or Myfortic (mycophenolate sodium), or generic).	Drug: methylprednisolone; Other Names: Medrol ; Biological: Anti-thymocyte Globulin (Rabbit); Other Names: Thymoglobulin ATG (Rabbit) ; Drug: Tacrolimus; There may be an opportunity to withdraw tacrolimus at week 40; Other Names: Prograf ; Drug: Mycophenolate mofetil; Mycophenolate mofetil will be administered at a target dose of 1000 mg by mouth twice daily (e.g., BID) beginning on the day of surgery or post-operative day 1 depending upon when during the day the surgery is completed (maximum MMF dosing is 2G per day). MMF will be adjusted based on clinical complications (such as neutropenia). Myfortic® (mycophenolate sodium) may be used as a replacement for MMF. Mycophenolate sodium will be dosed at 720 mg PO BID. Mycophenolate sodium will be adjusted based on clinical complications.; Other Names: MMF, mycophenolate sodium, CellCept
Experimental: Immunosuppression Including Belatacept Induction: 5 day course of methylprednisolone or equivalent; Induction: Anti-thymocyte Globulin (Rabbit); Maintenance Immunosuppression: Belatacept Maintenance Immunosuppression: Tacrolimus (or generic)- The site investigator will identify a starting tacrolimus dose at his or her discretion, in order to achieve the target trough levels no later than 5 days post-transplantation. Tacrolimus dosing will be initiated on the day of surgery or post-operative day 1 depending upon when during the day the surgery is completed. The dosage will be adjusted to achieve the following therapeutic trough levels: 5-8 ng/ml during the first 24 weeks post-transplant and then 3-5 ng/ml until day 280 (week 40). Subjects may be withdrawn if they meet all the criteria defined below. Maintenance Immunosuppression: Mycophenolate mofetil (or Myfortic (mycophenolate sodium), or generic).	Biological: Belatacept; The first dose of belatacept will be administered approximately 24-48 hours after the last dose of Anti-Thymocyte Globulin (Rabbit).; Other Names: NULOJIX ; Drug: methylprednisolone; Other Names: Medrol ; Biological: Anti-thymocyte Globulin (Rabbit); Other Names: Thymoglobulin ATG (Rabbit) ; Drug: Tacrolimus; There may be an opportunity to withdraw tacrolimus at week 40; Other Names: Prograf ; Drug: Mycophenolate mofetil; Mycophenolate mofetil will be administered at a target dose of 1000 mg by mouth twice daily (e.g., BID) beginning on the day of surgery or post-operative day 1 depending upon when during the day the surgery is completed (maximum MMF dosing is 2G per day). MMF will be adjusted based on clinical complications (such as neutropenia). Myfortic® (mycophenolate sodium) may be used as a replacement for MMF. Mycophenolate sodium will be dosed at 720 mg PO BID. Mycophenolate sodium will be adjusted based on clinical complications.; Other Names: MMF, mycophenolate sodium, CellCept

Outcome Measures

Primary Outcome Measures

1. Mean Estimated Glomerular Filtration Rate (eGFR) Calculated for Each Treatment Group Using the CKD-EPI Equation at Wk 52 Post-Transplant [Week 52 Post-Transplant]

   eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI): A score of ≥90 means kidney function is normal. A score between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease. Scores between 30 and 59 indicates moderately reduced kidney function. Scores between 15 and 29 indicate severely reduced kidney function. Scores below 15 indicate very severe or end stage kidney failure.

Secondary Outcome Measures

1. Count of Participants With eGFR < 60 mL/Min/1.73 m^2 Measured by CKD-EPI at Wk 52 Post-Transplant [Week 52 Post-Transplant]

   eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI): A score of ≥90 means kidney function is normal. A score between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease. Scores between 30 and 59 indicates moderately reduced kidney function. Scores between 15 and 29 indicate severely reduced kidney function. Scores below 15 indicate very severe or end stage kidney failure.

2. Count of Participants by CKD Stage at Wk 52 Post-Transplant [Week 52 Post-Transplant]

   The stages of Chronic Kidney Disease are defined using the participant's GFR value: Stage 1 if GFR value is ≥90 ( kidney function is normal) Stage 2 if 60 ≤ GFR < 90 (mildly reduced kidney function, pointing to kidney disease) Stage 3A if 45 ≤ GFR < 60* Stage 3B if 30 ≤ GFR < 45* Stage 4 if 15 ≤ GFR < 30 (severely reduced kidney function) Stage 5 if GFR < 15 (severe or end stage kidney failure). Stages 3A and 3B indicate moderately reduced kidney function.*

3. Count of Participants With Defined CKD Stage 4 or 5 at Wk 52 Post-Transplant [Week 52 Post-Transplant]

   The stages of Chronic Kidney Disease (CKD) are defined using the participant's GFR value: Stage 1 if GFR value is ≥ 90 (kidney function is normal) Stage 2 if 60 ≤ GFR < 90 (mildly reduced kidney function, pointing to kidney disease) Stage 3A if 45 <= GFR < 60* Stage 3B if 30 <= GFR < 45* Stage 4 if 15 ≤ GFR < 30 (severely reduced kidney function) Stage 5 if GFR < 15 (severe or end stage kidney failure). Stages 3A abd 3B indicate moderately reduced kidney function.*

4. Mean Calculated eGFR Using MDRD 4 Variable Model at Wk 52 Post-Transplant [Week 52 Post-Transplant]

   The estimated Glomerular Filtration Rate (eGFR) was calculated using the Modification of Diet in Renal Disease equation (MDRD): A score of ≥ 90 means kidney function is normal. A score between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease. Scores between 30 and 59 indicates moderately reduced kidney function. Scores between 15 and 29 indicate severely reduced kidney function. Scores below 15 indicate severe or endstage kidney failure.

5. The Slope of eGFR by CKD-EPI Over Time Based on Serum Creatinine Post-Transplant [Day 28 through Week 52 Post-Transplant]

   The estimated Glomerular Filtration Rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI): A score of ≥ 90 means kidney function is normal. A score between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease. Scores between 30 and 59 indicates moderately reduced kidney function. Scores between 15 and 29 indicate severely reduced kidney function. Scores below 15 indicate very severe or endstage kidney failure. An estimate of the slope, or change over time, in eGFR was produced using standard statistical linear modeling procedures. The estimate was then re-scaled so that it could be interpreted as a change in eGFR per month. Positive numbers indicate increasing kidney function. Larger numbers indicate greater change in kidney function.

6. Count of Participants With Successful Discontinuation of Tacrolimus in Recipients Randomized to the Investigational Arm [Week 40 through week 48 Post-Transplant]

   Participants achieved successful discontinuation if they were able to discontinue (e.g., off tacrolimus therapy completely) over a 4-8 weeks after tacrolimus withdrawal was initiated at week 40.

7. Count of Participants With Delayed Graft Function at Wk 52 Post-Transplant [Transplant through Week 52 Post-Transplant]

   Delayed grafted function is defined as dialysis in the first week on one or more occasions for any indication other than the treatment of acute hyperkalemia in the setting of otherwise acceptable renal function.

8. Count of Participants With Full Pancreatic Graft Function (Insulin Independent) at Wk 52 Post-Transplant [Week 52 Post-Transplant]

   Participants with full pancreatic graft functions are defined as those that no longer require exogenous insulin therapy.

9. Count of Participants With Evidence of Partial Pancreatic Graft Function at Week 52 Post-Transplant [Week 52 Post-Transplant]

   C-peptide is a measure of pancreatic function. The definition of partial pancreatic graft function: a fasting C-peptide levels >0.3ng.mL (0.1nmol.L) plus the participant's continued requirement for exogenous insulin or oral hypoglycemic agent(s).

10. Count of Participants With Evidence of Pancreatic Loss at Week 52 Post-Transplant [Week 52 Post-Transplant]

    C-peptide is a measure of pancreatic function. The definition of pancreatic loss: a C-peptide value of <0.3 ng/mL.

11. HbA1c at Baseline (Pre-Transplant) Through Wk 52 Post-Transplant [Baseline (Pre-Transplant) and Days 28, 84, and Weeks 28, 36, and 52]

    Hemoglobin A1c (HbA1c) measures the average blood glucose levels over 8-12 weeks, thus acting as a useful long-term gauge of blood glucose control: A value below 6.0% reflects normal levels, 6.0% to 6.4% reflects prediabetes, and a value of ≥ 6.5% reflects diabetes.

12. Fasting Blood Sugar (FBS) From Baseline (Pre-Transplant) Through Wk 52 Post-Transplant [Baseline (Pre-Transplant) and Days 28, 84, and Weeks 28, 36, and 52]

    Fasting blood sugar (e.g., glucose) test is used to help diagnose diabetes, prediabetes, and gestational diabetes. Reference fasting blood sugar (glucose) values: 70 to 99 mg/dL is normal 100 to 125 mg/dL is considered prediabetes 126 mg/dL or higher on two separate tests is considered diabetes.

13. Standardized Blood Pressure Measurement From Baseline (Pre-Transplant) Through Wk 52 Post-Transplant [Baseline (Pre-Transplant) and Days 28, 84, and Weeks 28, 36, and 52]

    A blood pressure measurement consists of two numbers: the systolic and diastolic pressures. Systolic pressure measures the pressure in blood vessels when the heart beats. Diastolic pressure measures the pressure in blood vessels between beats of the heart. Systolic measures of <120 and diastolic measures of <80 are considered normal. Systolic measures of 120-139 and diastolic measures of 80-89 are considered at risk (or pre-hypertension). Systolic measures of ≥140 and diastolic measures of ≥90 are considered high.

14. Count of Participants With Use of Anti-hypertensive Medication From Baseline (Pre-Transplant) Through Wk 52 Post-Transplant [Baseline (Pre-Transplant) and Days 28, 84, and Weeks 28, 36, and 52]

    Anti-hypertensive medications are a class of drugs that are used to treat hypertension. The medications seek to prevent the complications of high blood pressure, such as stoke and myocardial infarction.

15. Fasting Lipid Profile at Baseline (Pre-Transplant) [Baseline (Pre-Transplant)]

    A fasting lipid profiles measures total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels. These measurements are used in assessing one's risk of cardiovascular disease. Target ranges for each of these measures are provided: Total cholesterol: 75-169 mg/dL if age ≤20; 100-199 mg/dL if age ≥ 21; high values indicate risk of cardiovascular disease LDL cholesterol: <70 mg/dL for people with documented cardiovascular disease or metabolic syndrome; <100 mg/dL for people considered high risk for cardiovascular disease; <130 mg/dL for people considered low risk for cardiovascular disease; high values indicate risk of cardiovascular disease HDL cholesterol: 40mg/dL and higher; high values indicate reduced risk of cardiovascular disease Non-HDL cholesterol: 30 mg/dL above the target value for LDL cholesterol; high values indicate risk of cardiovascular disease and Triglycerides: <150 mg/dL; high values indicate risk of cardiovascular disease.

16. Fasting Lipid Profile at Wk 28 Post-Transplant [Week 28 Post-Transplant]

    A fasting lipid profiles measures total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels. These measurements are used in assessing one's risk of cardiovascular disease. Target ranges for each of these measures are provided: Total cholesterol: 75-169 mg/dL if age ≤20; 100-199 mg/dL if age ≥ 21; high values indicate risk of cardiovascular disease LDL cholesterol: <70 mg/dL for people with documented cardiovascular disease or metabolic syndrome; <100 mg/dL for people considered high risk for cardiovascular disease; <130 mg/dL for people considered low risk for cardiovascular disease; high values indicate risk of cardiovascular disease HDL cholesterol: 40mg/dL and higher; high values indicate reduced risk of cardiovascular disease Non-HDL cholesterol: 30 mg/dL above the target value for LDL cholesterol; high values indicate risk of cardiovascular disease and Triglycerides: <150 mg/dL; high values indicate risk of cardiovascular disease.

17. Lipid Profile at Wk 52 Post-Transplant [Week 52 Post-Transplant]

    A fasting lipid profiles measures total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels. These measurements are used in assessing one's risk of cardiovascular disease. Target ranges for each of these measures are provided: Total cholesterol: 75-169 mg/dL if age ≤ 20; 100-199 mg/dL if age ≥ 21; high values indicate risk of cardiovascular disease LDL cholesterol: <70 mg/dL for people with documented cardiovascular disease or metabolic syndrome; <100 mg/dL for people considered high risk for cardiovascular disease; <130 mg/dL for people considered low risk for cardiovascular disease; high values indicate risk of cardiovascular disease HDL cholesterol: 40mg/dL and higher; high values indicate reduced risk of cardiovascular disease Non-HDL cholesterol: 30 mg/dL above the target value for LDL cholesterol; high values indicate risk of cardiovascular disease and Triglycerides: <150 mg/dL; high values indicate risk of cardiovascular disease.

18. Count of Participants With Use of Lipid Lowering Medications at Baseline, Wk 28 and Wk 52 Post-Transplant [Baseline (Pre-Transplant), Week 28, and Week 52]

    Lipid lowering medications are used in the treatment of high levels of fats (lipids), such as cholesterol in blood

19. Count of Participants With Acute Rejection (AR) of Kidney or Pancreatic Transplant During the First 52 Wks Post-Transplant [Transplant through Week 52]

    Biopsy-proven acute rejection (AR) of the kidney (renal) or pancreas during the first 52 weeks post-transplant. AR grading using standard Banff* criteria. For both kidney and pancreas, AR is defined as a grade ≥1. AR for the kidney: Banff 2007 criteria. Severity of AR is graded by as IA, IB, IIA, IIB, or III, with IA defined as the mildest form of AR and III being the most severe. AR for the pancreas: Banff 2011 Criteria. Severity of AR is graded as I, II, or III, with I defined as the mildest form of AR and III being the most severe.

20. Severity Grade of First Biopsy-Proven Acute Rejection (AR) During the First 52 Weeks Post-Transplant [Transplant through Week 52]

    AR grading using standard Banff* criteria. For both kidney and pancreas, AR is defined as a grade ≥1. AR for the kidney: Banff 2007 criteria. Severity of AR is graded by as IA, IB, IIA, IIB, or III, with IA defined as the mildest form of AR and III being the most severe. AR for the pancreas: Banff 2011 Criteria. Severity of AR is graded is I, II, or III, with I defined as the mildest form of AR and III being the most severe.

21. Count of Participants With Biopsy-Proven Humoral Rejection During the First 52 Weeks Post-Transplant [Transplant through Week 52]

    Humoral rejection (i.e., antibody mediated rejection) of: the kidney as defined by diffusely positive staining for C4d, presence of circulating anti-donor antibodies, and morphologic evidence of acute tissue injury determined by local pathology and, the pancreas as defined by the presence of circulating anti-donor antibodies, and histopathological data including morphologic evidence of microvascular tissue injury and C4d staining in interacinar capillaries determined by local pathology.

22. Count of Participants With De Novo Anti-Donor Antibodies or Anti-Human Leukocyte Antigen (HLA) Antibodies During the First 52 Weeks Post-Transplant [Transplant through Week 52]

    The de novo development of donor-specific antibody (DSA) is associated with an increased risk of graft rejection. The presence of anti-Histocompatibility Antigen (HLA) antibodies (alloantibodies) is associated with increased risk of acute and chronic injury to the transplant allograft.

23. Type of Treatment(s) Participants Received for Biopsy-Proven Renal Allograft Rejection During the First 52 Weeks Post-Transplant [Transplant through Week 52]

    Participants are stratified by kidney biopsy results/treatment received. In the event of a for cause renal (kidney) biopsy: -The diagnosis of acute cellular rejection (ACR) using the Banff 2007 renal allograft pathology criteria. These criteria for renal allograft biopsies is an international histopathological classification standard. ACR is defined by a renal biopsy demonstrating a Banff 2007 classification of Grade IA or greater, with higher scores indicating more severe rejection. (Ref: Solez K, Colvin RB et al. Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant 2008 8(4): 753-60). Acronyms and abbreviations: ACR=Acute Cellular Rejection* Normal* Borderline* (criteria for ACR not fulfilled) Gd.=Grade* IFTA=Interstitial Fibrosis and Tubular Atrophy* ATG=Anti-thymocyte globulin therapy IVIG=Intravenous Immunoglobulin therapy PO=Orally QD=Daily *Banff 2007 renal allograft pathology criteria

24. Type of Treatment(s) Participants Received for Biopsy-Proven Pancreatic Allograft Rejection During the First 52 Weeks Post-Transplant [Transplant through Week 52]

    Participants are stratified by kidney biopsy results/treatment received. Upon having a for-cause biopsy performed, persons often receive treatment for rejection based on the biopsy results, which may or may not reveal signs of rejection. Details of biopsy findings and corresponding treatment are provided for each instance of treatment for rejection. Results summary format: biopsy results; treatment. Acronyms and abbreviations: ACR=Acute Cellular Rejection IFTA=Interstitial Fibrosis and Tubular Atrophy ATG=Anti-thymocyte globulin therapy IVIG=Intravenous Immunoglobulin therapy Gd =Grade PO=Orally QD=Daily

25. Count of Participants With Event of Death, Graft Loss, or Undetectable C-peptide [Transplant through Week 52 Post-Transplant]

    This measure counts death, graft loss, or undetectable C-peptide value (e.g., C-peptide <0.3 ng/mL) occurring at any point post-transplant and independent of each other. Kidney Graft Loss was defined as 90 consecutive days of dialysis dependency. Pancreas graft loss was defined as returning to exogenous insulin therapy or initiation of oral hypoglycemic agents for greater than 30 days. Factitious hypoglycemia due to surreptitious insulin administration results in elevated serum insulin levels and low or undetectable C-peptide levels.

26. Count of Participants With the Occurrence of Adverse Events (AEs) and Serious Adverse Events (SAEs) [From Enrollment (Pre-Transplant) to Week 52 Post-Transplant]

    Adverse events were collected systematically. Counts of all participants who experienced at least one adverse event (AEs, SAEs) by assigned treatment group. Refer to the Serious Adverse Events and Other Adverse Events tables for more detail.

27. Count of Participants With an Infectious Disease Serious Adverse Event(s) Requiring Hospitalization or Systemic Therapy [Transplant through Week 52 Post-Transplant]

    Infections were required to be reported as a serious adverse event if they required either inpatient hospitalization or prolongation of a current hospitalization. Displayed are counts of all participants who experienced infection(s) as an adverse event, by treatment group.

28. Count of Participant Diagnosed With BK Polyoma Virus (BKV) and Cytomegalovirus (CMV) Viremia As Adverse Events [Transplant through Week 52 Post-Transplant]

    Viral infections following renal transplantation is a significant source of recipient morbidity and mortality, and a significant cause of allograft dysfunction and loss. Specific viruses were monitored during this study using participant blood samples. Displayed are counts of participants who experienced BKV and CMV viremia as adverse events, diagnosed by test results from the local clinical pathology laboratory.

29. Count of Participants Diagnosed With Epstein-Barr Virus (EBV) Infection as an Adverse Event [Transplant through Week 52 Post-Transplant]

    Viral infections following renal transplantation is a significant source of recipient morbidity and mortality, and a significant cause of allograft dysfunction and loss. Specific viruses were monitored during this study using participant blood samples. Displayed are counts of all participants diagnosed with EBV infection as an adverse event by EBV test(s), diagnosed by test results from the local clinical pathology laboratory.

30. Count of Participants Diagnosed With Malignancy as an Adverse Event [Transplant through Week 52 Post-Transplant]

    An increased risk/incidence of malignancy is a recognized complication of immunosuppression in recipients of organ transplants. In Phase 3 clinical trials, overall malignancy rates were similar across all treatment groups, with the exception of posttransplant lymphoproliferative disease (PTLD).Displayed are counts of all participants who experienced malignancy reported as an adverse event.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Ability to understand and provide written informed consent;

• Candidate for a primary simultaneous kidney and pancreas allograft with random c-peptide <0.3 ng/mL;

• No known contraindications to study therapy using NULOJIX® (belatacept);

• Female subjects of childbearing potential must have a negative pregnancy test upon study entry;

• Female and male participants with reproductive potential must agree to use FDA approved methods of birth control during participation in the study and for 4 months following study completion;

• No donor specific antibodies prior to transplant that are considered to be of clinical significance by the site investigator;

• Negative crossmatch, actual or virtual, or a Panel Reactive Antibodies (PRA) of 0% on historic and admission sera, as determined by each participating study center;

• A documented negative Tuberculosis (TB) test within the 12 months prior to transplant. If documentation is not present at the time of transplantation, and the subject does not have any risk factors for TB, a TB-specific interferon gamma release assay (IGRA) may be performed.

Exclusion Criteria:

• Need for multi-organ transplantation other than a kidney and pancreas;

• Recipient of previous organ transplant;

• Epstein-Barr Virus (EBV) sero-negative recipients or recipients whose EBV serostatus is unknown prior to the time of transplantation;

• Individuals infected by the hepatitis B or C viruses or HIV;

• Individuals who have required treatment with systemic prednisone or other immunosuppressive drugs within 1 year prior to transplant;

• Individuals previously treated with NULOJIX® (belatacept);

• Any condition that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements;

• Use of investigational drugs within 4 weeks of enrollment;

• Known hypersensitivity to mycophenolate mofetil (MMF)or any of the drug's components;

• Administration of live attenuated vaccine(s) within 8 weeks of enrollment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	University of California San Francisco Medical Center	San Francisco	California	United States	94143-0780
3	Emory University	Atlanta	Georgia	United States	30322
4	Indiana University Hospital	Indianapolis	Indiana	United States	46202
5	University of Wisconsin	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)
• Clinical Trials in Organ Transplantation
• Rho Federal Systems Division, Inc.
• Bristol-Myers Squibb

Investigators

• Principal Investigator: Kenneth Newell, MD, PhD, Emory University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 28, 2016
• Informed Consent Form - Jun 28, 2016

More Information

Additional Information:

• National Institute of Allergy and Infectious Diseases (NIAID) website
• Division of Allergy, Immunology, and Transplantation (DAIT) website
• Clinical Trials in Organ Transplantation (CTOT) website

Publications

None provided.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT01790594
• Other Study ID Numbers: DAIT CTOT-15; U01AI084150; NIAID CRMS ID#: 20117; SDY1433
• First Posted: Feb 13, 2013
• Last Update Posted: Jul 20, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): transplantation; kidney; pancreas; immunosuppression; calcineurin inhibitor (CNI)
• Additional relevant MeSH terms: Mycophenolic Acid; Methylprednisolone; Abatacept; Tacrolimus; Thymoglobulin; Antilymphocyte Serum

Study Results

Participant Flow

Recruitment Details	Five sites in the United States recruited and enrolled 46 participants into this trial.

Arm/Group Title	Investigational	Control	Enrolled, Not Randomized
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Subjects who signed informed consent and were thus enrolled, but were not randomized to study treatment.
Period Title: Overall Study
STARTED	22	21	3
COMPLETED	17	18	0
NOT COMPLETED	5	3	3

Baseline Characteristics

Arm/Group Title	Investigational	Control	Total
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Total of all reporting groups
Overall Participants	22	21	43
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	22 100%	21 100%	43 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.7 (7.10)	38.8 (6.98)	39.3 (6.97)
Sex: Female, Male (Count of Participants)
Female	10 45.5%	8 38.1%	18 41.9%
Male	12 54.5%	13 61.9%	25 58.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 9.1%	1 4.8%	3 7%
Not Hispanic or Latino	17 77.3%	18 85.7%	35 81.4%
Unknown or Not Reported	3 13.6%	2 9.5%	5 11.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	1 4.8%	1 2.3%
Black or African American	3 13.6%	5 23.8%	8 18.6%
White	18 81.8%	14 66.7%	32 74.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 4.5%	1 4.8%	2 4.7%
Region of Enrollment (participants) [Number]
United States	22 100%	21 100%	43 100%

Outcome Measures

1. Primary Outcome

Title	Mean Estimated Glomerular Filtration Rate (eGFR) Calculated for Each Treatment Group Using the CKD-EPI Equation at Wk 52 Post-Transplant
Description	eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI): A score of ≥90 means kidney function is normal. A score between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease. Scores between 30 and 59 indicates moderately reduced kidney function. Scores between 15 and 29 indicate severely reduced kidney function. Scores below 15 indicate very severe or end stage kidney failure.
Time Frame	Week 52 Post-Transplant

Outcome Measure Data

Analysis Population Description

Intent-to-treat population with available data at week 52.

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	21	21
Mean (Standard Deviation) [mL/min/1.73m^2]	77.0 (22.6)	74.6 (19.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Investigational, Control
	Comments	The p-value compares Investigational arm and control arm.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.750
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.088
	Confidence Interval	(2-Sided) 95%; -11.067 to 15.242
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Count of Participants With eGFR < 60 mL/Min/1.73 m^2 Measured by CKD-EPI at Wk 52 Post-Transplant
Description	eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI): A score of ≥90 means kidney function is normal. A score between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease. Scores between 30 and 59 indicates moderately reduced kidney function. Scores between 15 and 29 indicate severely reduced kidney function. Scores below 15 indicate very severe or end stage kidney failure.
Time Frame	Week 52 Post-Transplant

Outcome Measure Data

Analysis Population Description

Intent-to-treat population

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	22	21
Count of Participants [Participants]	5 22.7%	5 23.8%

3. Secondary Outcome

Title	Count of Participants by CKD Stage at Wk 52 Post-Transplant
Description	The stages of Chronic Kidney Disease are defined using the participant's GFR value: Stage 1 if GFR value is ≥90 ( kidney function is normal) Stage 2 if 60 ≤ GFR < 90 (mildly reduced kidney function, pointing to kidney disease) Stage 3A if 45 ≤ GFR < 60* Stage 3B if 30 ≤ GFR < 45* Stage 4 if 15 ≤ GFR < 30 (severely reduced kidney function) Stage 5 if GFR < 15 (severe or end stage kidney failure). Stages 3A and 3B indicate moderately reduced kidney function.*
Time Frame	Week 52 Post-Transplant

Outcome Measure Data

Analysis Population Description

Intent-to-treat population

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	21	21
Stage 1	5 22.7%	5 23.8%
Stage 2	11 50%	11 52.4%
Stage 3A	2 9.1%	4 19%
Stage 3B	3 13.6%	1 4.8%
Stage 4	0 0%	0 0%
Stage 5	0 0%	0 0%

4. Secondary Outcome

Title	Count of Participants With Defined CKD Stage 4 or 5 at Wk 52 Post-Transplant
Description	The stages of Chronic Kidney Disease (CKD) are defined using the participant's GFR value: Stage 1 if GFR value is ≥ 90 (kidney function is normal) Stage 2 if 60 ≤ GFR < 90 (mildly reduced kidney function, pointing to kidney disease) Stage 3A if 45 <= GFR < 60* Stage 3B if 30 <= GFR < 45* Stage 4 if 15 ≤ GFR < 30 (severely reduced kidney function) Stage 5 if GFR < 15 (severe or end stage kidney failure). Stages 3A abd 3B indicate moderately reduced kidney function.*
Time Frame	Week 52 Post-Transplant

Outcome Measure Data

Analysis Population Description

Intent-to-treat population

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	22	21
Count of Participants [Participants]	0 0%	0 0%

5. Secondary Outcome

Title	Mean Calculated eGFR Using MDRD 4 Variable Model at Wk 52 Post-Transplant
Description	The estimated Glomerular Filtration Rate (eGFR) was calculated using the Modification of Diet in Renal Disease equation (MDRD): A score of ≥ 90 means kidney function is normal. A score between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease. Scores between 30 and 59 indicates moderately reduced kidney function. Scores between 15 and 29 indicate severely reduced kidney function. Scores below 15 indicate severe or endstage kidney failure.
Time Frame	Week 52 Post-Transplant

Outcome Measure Data

Analysis Population Description

Intent-to-treat population

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	21	21
Mean (Standard Deviation) [mL/min/1.73m^2]	68.7 (19.5)	67.0 (17.6)

6. Secondary Outcome

Title	The Slope of eGFR by CKD-EPI Over Time Based on Serum Creatinine Post-Transplant
Description	The estimated Glomerular Filtration Rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI): A score of ≥ 90 means kidney function is normal. A score between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease. Scores between 30 and 59 indicates moderately reduced kidney function. Scores between 15 and 29 indicate severely reduced kidney function. Scores below 15 indicate very severe or endstage kidney failure. An estimate of the slope, or change over time, in eGFR was produced using standard statistical linear modeling procedures. The estimate was then re-scaled so that it could be interpreted as a change in eGFR per month. Positive numbers indicate increasing kidney function. Larger numbers indicate greater change in kidney function.
Time Frame	Day 28 through Week 52 Post-Transplant

Outcome Measure Data

Analysis Population Description

Intent-to-treat population

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	22	21
Mean (Standard Deviation) [eGFR change over time (by month)]	0.1 (3.1)	-0.1 (2.5)

7. Secondary Outcome

Title	Count of Participants With Successful Discontinuation of Tacrolimus in Recipients Randomized to the Investigational Arm
Description	Participants achieved successful discontinuation if they were able to discontinue (e.g., off tacrolimus therapy completely) over a 4-8 weeks after tacrolimus withdrawal was initiated at week 40.
Time Frame	Week 40 through week 48 Post-Transplant

Outcome Measure Data

Analysis Population Description

Intent-to-treat population with available data

Arm/Group Title	Investigational
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	22
Count of Participants [Participants]	5 22.7%

8. Secondary Outcome

Title	Count of Participants With Delayed Graft Function at Wk 52 Post-Transplant
Description	Delayed grafted function is defined as dialysis in the first week on one or more occasions for any indication other than the treatment of acute hyperkalemia in the setting of otherwise acceptable renal function.
Time Frame	Transplant through Week 52 Post-Transplant

Outcome Measure Data

Analysis Population Description

Intent-to-treat population

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	22	21
Count of Participants [Participants]	1 4.5%	1 4.8%

9. Secondary Outcome

Title	Count of Participants With Full Pancreatic Graft Function (Insulin Independent) at Wk 52 Post-Transplant
Description	Participants with full pancreatic graft functions are defined as those that no longer require exogenous insulin therapy.
Time Frame	Week 52 Post-Transplant

Outcome Measure Data

Analysis Population Description

Intent-to-treat population

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	21	21
Count of Participants [Participants]	19 86.4%	21 100%

10. Secondary Outcome

Title	Count of Participants With Evidence of Partial Pancreatic Graft Function at Week 52 Post-Transplant
Description	C-peptide is a measure of pancreatic function. The definition of partial pancreatic graft function: a fasting C-peptide levels >0.3ng.mL (0.1nmol.L) plus the participant's continued requirement for exogenous insulin or oral hypoglycemic agent(s).
Time Frame	Week 52 Post-Transplant

Outcome Measure Data

Analysis Population Description

Intent-to-treat population with available data

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	18	17
Count of Participants [Participants]	1 4.5%	0 0%

11. Secondary Outcome

Title	Count of Participants With Evidence of Pancreatic Loss at Week 52 Post-Transplant
Description	C-peptide is a measure of pancreatic function. The definition of pancreatic loss: a C-peptide value of <0.3 ng/mL.
Time Frame	Week 52 Post-Transplant

Outcome Measure Data

Analysis Population Description

Intent-to-treat population with available data

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	18	17
Count of Participants [Participants]	1 4.5%	0 0%

12. Secondary Outcome

Title	HbA1c at Baseline (Pre-Transplant) Through Wk 52 Post-Transplant
Description	Hemoglobin A1c (HbA1c) measures the average blood glucose levels over 8-12 weeks, thus acting as a useful long-term gauge of blood glucose control: A value below 6.0% reflects normal levels, 6.0% to 6.4% reflects prediabetes, and a value of ≥ 6.5% reflects diabetes.
Time Frame	Baseline (Pre-Transplant) and Days 28, 84, and Weeks 28, 36, and 52

Outcome Measure Data

Analysis Population Description

Intent-to-treat population with available data

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	22	21
Baseline	8.6 (1.1)	8.5 (1.9)
Day 28	6.0 (0.6)	6.1 (0.6)
Day 84	4.8 (0.7)	4.9 (0.3)
Week 28	5.3 (1.3)	5.2 (0.5)
Week 36	5.3 (1.3)	5.1 (0.6)
Week 52	5.5 (1.6)	5.3 (0.5)

13. Secondary Outcome

Title	Fasting Blood Sugar (FBS) From Baseline (Pre-Transplant) Through Wk 52 Post-Transplant
Description	Fasting blood sugar (e.g., glucose) test is used to help diagnose diabetes, prediabetes, and gestational diabetes. Reference fasting blood sugar (glucose) values: 70 to 99 mg/dL is normal 100 to 125 mg/dL is considered prediabetes 126 mg/dL or higher on two separate tests is considered diabetes.
Time Frame	Baseline (Pre-Transplant) and Days 28, 84, and Weeks 28, 36, and 52

Outcome Measure Data

Analysis Population Description

Intent-to-treat population with available data

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	21	19
Baseline	183.3 (107.2)	217.3 (125.4)
Day 28	100.0 (15.3)	100.9 (20.5)
Day 84	96.0 (44.9)	89.7 (8.2)
Week 28	106.5 (84.7)	96.2 (22.6)
Week 36	96.0 (27.8)	87.2 (10.8)
Week 52	98.6 (37.5)	91.5 (12.1)

14. Secondary Outcome

Title	Standardized Blood Pressure Measurement From Baseline (Pre-Transplant) Through Wk 52 Post-Transplant
Description	A blood pressure measurement consists of two numbers: the systolic and diastolic pressures. Systolic pressure measures the pressure in blood vessels when the heart beats. Diastolic pressure measures the pressure in blood vessels between beats of the heart. Systolic measures of <120 and diastolic measures of <80 are considered normal. Systolic measures of 120-139 and diastolic measures of 80-89 are considered at risk (or pre-hypertension). Systolic measures of ≥140 and diastolic measures of ≥90 are considered high.
Time Frame	Baseline (Pre-Transplant) and Days 28, 84, and Weeks 28, 36, and 52

Outcome Measure Data

Analysis Population Description

Intent-to-treat population with available data

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	22	21
Systolic BP at Baseline	161.3 (26.1)	158.3 (23.7)
Systolic BP at Day 28	116.9 (15.4)	112.0 (16.8)
Systolic BP at Day 84	126.3 (19.2)	123.8 (18.6)
Systolic BP at Week 28	136.1 (22.7)	126.2 (23.8)
Systolic BP at Week 36	133.5 (20.5)	126.7 (10.6)
Systolic BP at Week 52	132.0 (18.8)	127.0 (15.4)
Diastolic BP at Baseline	82.7 (14.0)	85.2 (10.5)
Diastolic BP at Day 28	67.0 (8.4)	65.4 (9.2)
Diastolic BP at Day 84	72.8 (7.9)	73.4 (10.1)
Diastolic BP at Week 28	76.6 (8.8)	73.3 (10.4)
Diastolic BP at Week 36	76.5 (10.0)	76.8 (8.8)
Diastolic BP at Week 52	74.2 (8.6)	77.0 (7.6)

15. Secondary Outcome

Title	Count of Participants With Use of Anti-hypertensive Medication From Baseline (Pre-Transplant) Through Wk 52 Post-Transplant
Description	Anti-hypertensive medications are a class of drugs that are used to treat hypertension. The medications seek to prevent the complications of high blood pressure, such as stoke and myocardial infarction.
Time Frame	Baseline (Pre-Transplant) and Days 28, 84, and Weeks 28, 36, and 52

Outcome Measure Data

Analysis Population Description

Intent-to-treat population with available data

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	22	21
Baseline	18 81.8%	19 90.5%
Day 28	14 63.6%	10 47.6%
Day 84	11 50%	7 33.3%
Week 28	13 59.1%	11 52.4%
Week 36	13 59.1%	11 52.4%
Week 52	13 59.1%	11 52.4%

16. Secondary Outcome

Title	Fasting Lipid Profile at Baseline (Pre-Transplant)
Description	A fasting lipid profiles measures total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels. These measurements are used in assessing one's risk of cardiovascular disease. Target ranges for each of these measures are provided: Total cholesterol: 75-169 mg/dL if age ≤20; 100-199 mg/dL if age ≥ 21; high values indicate risk of cardiovascular disease LDL cholesterol: <70 mg/dL for people with documented cardiovascular disease or metabolic syndrome; <100 mg/dL for people considered high risk for cardiovascular disease; <130 mg/dL for people considered low risk for cardiovascular disease; high values indicate risk of cardiovascular disease HDL cholesterol: 40mg/dL and higher; high values indicate reduced risk of cardiovascular disease Non-HDL cholesterol: 30 mg/dL above the target value for LDL cholesterol; high values indicate risk of cardiovascular disease and Triglycerides: <150 mg/dL; high values indicate risk of cardiovascular disease.
Time Frame	Baseline (Pre-Transplant)

Outcome Measure Data

Analysis Population Description

Intent-to-treat population with available data

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	19	19
Tot. Chol. Baseline	142.8 (38.1)	140.5 (42.0)
Non-HDL Baseline	91.0 (28.0)	82.4 (42.0)
LDL Baseline	66.5 (28.0)	60.7 (32.9)
HDL Baseline	51.8 (19.0)	58.1 (16.2)
Triglyc. Baseline	120.9 (55.2)	107.5 (55.1)

17. Secondary Outcome

Title	Fasting Lipid Profile at Wk 28 Post-Transplant
Description	A fasting lipid profiles measures total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels. These measurements are used in assessing one's risk of cardiovascular disease. Target ranges for each of these measures are provided: Total cholesterol: 75-169 mg/dL if age ≤20; 100-199 mg/dL if age ≥ 21; high values indicate risk of cardiovascular disease LDL cholesterol: <70 mg/dL for people with documented cardiovascular disease or metabolic syndrome; <100 mg/dL for people considered high risk for cardiovascular disease; <130 mg/dL for people considered low risk for cardiovascular disease; high values indicate risk of cardiovascular disease HDL cholesterol: 40mg/dL and higher; high values indicate reduced risk of cardiovascular disease Non-HDL cholesterol: 30 mg/dL above the target value for LDL cholesterol; high values indicate risk of cardiovascular disease and Triglycerides: <150 mg/dL; high values indicate risk of cardiovascular disease.
Time Frame	Week 28 Post-Transplant

Outcome Measure Data

Analysis Population Description

Intent-to-treat population with available data

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	17	16
Tot. Chol. Week 28	159.9 (48.8)	149.2 (28.7)
Non-HDL Week 28	112.6 (45.4)	97.4 (27.9)
LDL Week 28	93.1 (43.9)	81.2 (28.5)
HDL Week 28	47.3 (15.1)	51.8 (11.8)
Triglyc. Week 28	93.2 (52.6)	87.8 (44.1)

18. Secondary Outcome

Title	Lipid Profile at Wk 52 Post-Transplant
Description	A fasting lipid profiles measures total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels. These measurements are used in assessing one's risk of cardiovascular disease. Target ranges for each of these measures are provided: Total cholesterol: 75-169 mg/dL if age ≤ 20; 100-199 mg/dL if age ≥ 21; high values indicate risk of cardiovascular disease LDL cholesterol: <70 mg/dL for people with documented cardiovascular disease or metabolic syndrome; <100 mg/dL for people considered high risk for cardiovascular disease; <130 mg/dL for people considered low risk for cardiovascular disease; high values indicate risk of cardiovascular disease HDL cholesterol: 40mg/dL and higher; high values indicate reduced risk of cardiovascular disease Non-HDL cholesterol: 30 mg/dL above the target value for LDL cholesterol; high values indicate risk of cardiovascular disease and Triglycerides: <150 mg/dL; high values indicate risk of cardiovascular disease.
Time Frame	Week 52 Post-Transplant

Outcome Measure Data

Analysis Population Description

Intent-to-treat population with available data

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	19	13
Tot. Chol. Week 52	164.2 (38.9)	162.8 (44.1)
Non-HDL Week 52	115.7 (38.1)	112.3 (38.5)
LDL Week 52	96.9 (36.5)	92.7 (33.1)
HDL Week 52	48.5 (16.7)	47.3 (12.8)
Triglyc. Week 52	88.6 (34.9)	95.4 (75.0)

19. Secondary Outcome

Title	Count of Participants With Use of Lipid Lowering Medications at Baseline, Wk 28 and Wk 52 Post-Transplant
Description	Lipid lowering medications are used in the treatment of high levels of fats (lipids), such as cholesterol in blood
Time Frame	Baseline (Pre-Transplant), Week 28, and Week 52

Outcome Measure Data

Analysis Population Description

Intent-to-treat population

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	22	21
Baseline	18 81.8%	18 85.7%
Week 28	19 86.4%	16 76.2%
Week 52	19 86.4%	16 76.2%

20. Secondary Outcome

Title	Count of Participants With Acute Rejection (AR) of Kidney or Pancreatic Transplant During the First 52 Wks Post-Transplant
Description	Biopsy-proven acute rejection (AR) of the kidney (renal) or pancreas during the first 52 weeks post-transplant. AR grading using standard Banff* criteria. For both kidney and pancreas, AR is defined as a grade ≥1. AR for the kidney: Banff 2007 criteria. Severity of AR is graded by as IA, IB, IIA, IIB, or III, with IA defined as the mildest form of AR and III being the most severe. AR for the pancreas: Banff 2011 Criteria. Severity of AR is graded as I, II, or III, with I defined as the mildest form of AR and III being the most severe.
Time Frame	Transplant through Week 52

Outcome Measure Data

Analysis Population Description

Intent-to-treat population

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	22	21
Kidney	2 9.1%	2 9.5%
Pancreas	5 22.7%	1 4.8%

21. Secondary Outcome

Title	Severity Grade of First Biopsy-Proven Acute Rejection (AR) During the First 52 Weeks Post-Transplant
Description	AR grading using standard Banff* criteria. For both kidney and pancreas, AR is defined as a grade ≥1. AR for the kidney: Banff 2007 criteria. Severity of AR is graded by as IA, IB, IIA, IIB, or III, with IA defined as the mildest form of AR and III being the most severe. AR for the pancreas: Banff 2011 Criteria. Severity of AR is graded is I, II, or III, with I defined as the mildest form of AR and III being the most severe.
Time Frame	Transplant through Week 52

Outcome Measure Data

Analysis Population Description

Intent-to-treat population

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	22	21
Kidney First Grade IA	0 0%	1 4.8%
Kidney First Grade IB	1 4.5%	0 0%
Kidney First Grade IIA	0 0%	1 4.8%
Kidney First Grade IIB	1 4.5%	0 0%
Pancreas First Grade I	4 18.2%	0 0%
Pancreas First Grade II	1 4.5%	1 4.8%

22. Secondary Outcome

Title	Count of Participants With Biopsy-Proven Humoral Rejection During the First 52 Weeks Post-Transplant
Description	Humoral rejection (i.e., antibody mediated rejection) of: the kidney as defined by diffusely positive staining for C4d, presence of circulating anti-donor antibodies, and morphologic evidence of acute tissue injury determined by local pathology and, the pancreas as defined by the presence of circulating anti-donor antibodies, and histopathological data including morphologic evidence of microvascular tissue injury and C4d staining in interacinar capillaries determined by local pathology.
Time Frame	Transplant through Week 52

Outcome Measure Data

Analysis Population Description

Intent-to-treat population with available data

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	22	21
Kidney	0 0%	0 0%
Pancreas	0 0%	0 0%

23. Secondary Outcome

Title	Count of Participants With De Novo Anti-Donor Antibodies or Anti-Human Leukocyte Antigen (HLA) Antibodies During the First 52 Weeks Post-Transplant
Description	The de novo development of donor-specific antibody (DSA) is associated with an increased risk of graft rejection. The presence of anti-Histocompatibility Antigen (HLA) antibodies (alloantibodies) is associated with increased risk of acute and chronic injury to the transplant allograft.
Time Frame	Transplant through Week 52

Outcome Measure Data

Analysis Population Description

Intent-to-treat population with available data

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	22	20
De novo DSA	0 0%	0 0%
Anti-HLA	2 9.1%	1 4.8%

24. Secondary Outcome

Title	Type of Treatment(s) Participants Received for Biopsy-Proven Renal Allograft Rejection During the First 52 Weeks Post-Transplant
Description	Participants are stratified by kidney biopsy results/treatment received. In the event of a for cause renal (kidney) biopsy: -The diagnosis of acute cellular rejection (ACR) using the Banff 2007 renal allograft pathology criteria. These criteria for renal allograft biopsies is an international histopathological classification standard. ACR is defined by a renal biopsy demonstrating a Banff 2007 classification of Grade IA or greater, with higher scores indicating more severe rejection. (Ref: Solez K, Colvin RB et al. Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant 2008 8(4): 753-60). Acronyms and abbreviations: ACR=Acute Cellular Rejection* Normal* Borderline* (criteria for ACR not fulfilled) Gd.=Grade* IFTA=Interstitial Fibrosis and Tubular Atrophy* ATG=Anti-thymocyte globulin therapy IVIG=Intravenous Immunoglobulin therapy PO=Orally QD=Daily *Banff 2007 renal allograft pathology criteria
Time Frame	Transplant through Week 52

Outcome Measure Data

Analysis Population Description

Intent-to-treat population with available data. All participants were considered evaluable for rejection. Only 'for cause' biopsies were performed post-transplant.

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	22	21
Borderline/None	1 4.5%	0 0%
Borderline/Pulse Steroids	0 0%	1 4.8%
Borderline, IFTA-Gd. I/Pulse Steroids, IVIG	0 0%	1 4.8%
ACR-Gd. IA/ATG, Pulse Steroids	0 0%	1 4.8%
ACR-Gd. IB/ATG, Pulse Steroids	1 4.5%	0 0%
ACR-Gd. IIA/ATG, Pulse Steroids	0 0%	1 4.8%
ACR-Gd. IIB/ATG, Pulse Steroids	1 4.5%	0 0%
IFTA-Gd. I/None	1 4.5%	0 0%
IFTA-Gd. I/Potassium citrate	2 9.1%	0 0%
Normal/Steroids QD	0 0%	1 4.8%
No grade reported/IVIG	1 4.5%	0 0%
No grade reported/None	1 4.5%	4 19%
Normal/None	3 13.6%	2 9.5%

25. Secondary Outcome

Title	Type of Treatment(s) Participants Received for Biopsy-Proven Pancreatic Allograft Rejection During the First 52 Weeks Post-Transplant
Description	Participants are stratified by kidney biopsy results/treatment received. Upon having a for-cause biopsy performed, persons often receive treatment for rejection based on the biopsy results, which may or may not reveal signs of rejection. Details of biopsy findings and corresponding treatment are provided for each instance of treatment for rejection. Results summary format: biopsy results; treatment. Acronyms and abbreviations: ACR=Acute Cellular Rejection IFTA=Interstitial Fibrosis and Tubular Atrophy ATG=Anti-thymocyte globulin therapy IVIG=Intravenous Immunoglobulin therapy Gd =Grade PO=Orally QD=Daily
Time Frame	Transplant through Week 52

Outcome Measure Data

Analysis Population Description

Intent-to-treat population with available data. Only 'for cause' biopsies were performed post-transplant.

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	22	21
ACR-Gd. I/ATG	1 4.5%	0 0%
ACR-Gd. I/ATG, Pulse Steroids	1 4.5%	0 0%
ACR-Gd. I/ATG, Pulse Steroids, IVIG	1 4.5%	0 0%
ACR-Gd. I, IFTA-Gd. I/Pulse Steroids, Solumedrol,	1 4.5%	0 0%
ACR-Gd. II/ATG, Pulse Steroids	1 4.5%	1 4.8%
No grade reported/None	1 4.5%	0 0%

26. Secondary Outcome

Title	Count of Participants With Event of Death, Graft Loss, or Undetectable C-peptide
Description	This measure counts death, graft loss, or undetectable C-peptide value (e.g., C-peptide <0.3 ng/mL) occurring at any point post-transplant and independent of each other. Kidney Graft Loss was defined as 90 consecutive days of dialysis dependency. Pancreas graft loss was defined as returning to exogenous insulin therapy or initiation of oral hypoglycemic agents for greater than 30 days. Factitious hypoglycemia due to surreptitious insulin administration results in elevated serum insulin levels and low or undetectable C-peptide levels.
Time Frame	Transplant through Week 52 Post-Transplant

Outcome Measure Data

Analysis Population Description

Intent-to-treat population with available data.

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	22	21
Death	1 4.5%	0 0%
Kidney Graft Loss	0 0%	0 0%
Pancreas Graft Loss	1 4.5%	0 0%
Undetectable C-peptide	0 0%	0 0%

27. Secondary Outcome

Title	Count of Participants With the Occurrence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	Adverse events were collected systematically. Counts of all participants who experienced at least one adverse event (AEs, SAEs) by assigned treatment group. Refer to the Serious Adverse Events and Other Adverse Events tables for more detail.
Time Frame	From Enrollment (Pre-Transplant) to Week 52 Post-Transplant

Outcome Measure Data

Analysis Population Description

Intent-to-treat population

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	22	21
All Adverse Events	22 100%	21 100%
Serious Adverse Events	20 90.9%	19 90.5%

28. Secondary Outcome

Title	Count of Participants With an Infectious Disease Serious Adverse Event(s) Requiring Hospitalization or Systemic Therapy
Description	Infections were required to be reported as a serious adverse event if they required either inpatient hospitalization or prolongation of a current hospitalization. Displayed are counts of all participants who experienced infection(s) as an adverse event, by treatment group.
Time Frame	Transplant through Week 52 Post-Transplant

Outcome Measure Data

Analysis Population Description

Intent-to-treat population

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	22	21
Count of Participants [Participants]	11 50%	11 52.4%

29. Secondary Outcome

Title	Count of Participant Diagnosed With BK Polyoma Virus (BKV) and Cytomegalovirus (CMV) Viremia As Adverse Events
Description	Viral infections following renal transplantation is a significant source of recipient morbidity and mortality, and a significant cause of allograft dysfunction and loss. Specific viruses were monitored during this study using participant blood samples. Displayed are counts of participants who experienced BKV and CMV viremia as adverse events, diagnosed by test results from the local clinical pathology laboratory.
Time Frame	Transplant through Week 52 Post-Transplant

Outcome Measure Data

Analysis Population Description

Intent-to-treat population

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	22	21
BK Viremia	8 36.4%	3 14.3%
CMV Viremia	5 22.7%	3 14.3%

30. Secondary Outcome

Title	Count of Participants Diagnosed With Epstein-Barr Virus (EBV) Infection as an Adverse Event
Description	Viral infections following renal transplantation is a significant source of recipient morbidity and mortality, and a significant cause of allograft dysfunction and loss. Specific viruses were monitored during this study using participant blood samples. Displayed are counts of all participants diagnosed with EBV infection as an adverse event by EBV test(s), diagnosed by test results from the local clinical pathology laboratory.
Time Frame	Transplant through Week 52 Post-Transplant

Outcome Measure Data

Analysis Population Description

Intent-to-treat population

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	22	21
Count of Participants [Participants]	0 0%	0 0%

31. Secondary Outcome

Title	Count of Participants Diagnosed With Malignancy as an Adverse Event
Description	An increased risk/incidence of malignancy is a recognized complication of immunosuppression in recipients of organ transplants. In Phase 3 clinical trials, overall malignancy rates were similar across all treatment groups, with the exception of posttransplant lymphoproliferative disease (PTLD).Displayed are counts of all participants who experienced malignancy reported as an adverse event.
Time Frame	Transplant through Week 52 Post-Transplant

Outcome Measure Data

Analysis Population Description

Intent-to-treat population

Arm/Group Title	Investigational	Control
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.	Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.
Measure Participants	22	21
Count of Participants [Participants]	0 0%	0 0%

Adverse Events

Time Frame	Transplantation until end of study (up to 76 weeks)
Arm/Group Title	Investigational		Control		Enrolled, Not Randomized
Arm/Group Description	Induction: Methylprednisolone (MEDROL) was administered at a dose of 500 mg on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Belatacept (NULOJIX) was given at a dose of 10 mg/kg on days 5, 14, 28, 56, and 84. After 84 days participants received 5 mg/kg every 4 weeks until the completion of the trial. Site investigator determined the initial dose of tacrolimus (tac) started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 5-8 ng/ml during the first 24 weeks, and adjusted to 3-5 ng/ml until week 40. If eligible, at week 40 tac withdrawal was initiated over a 4-8 week period. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.		Induction: 500 mg of MEDROL was administered on the day of transplant, and tapered to 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, 30 mg on day 4, and 0 mg on day 5. A target dose of 6 mg/kg over 3 to 4 days of Thymoglobulin was administered via intravenous infusion. Maintenance: Site investigator determined the initial dose of tacrolimus (tac) that started on the day of transplant or day 1. Dosing was adjusted to achieve a target trough of 8-12 ng/ml during the first 24 weeks, and adjusted to 5-8 ng/ml thereafter. Mycophenolate Mofetil (MMF) or equivalent was administered at a target dose of 1000 mg PO or IV BID starting on the day of transplant or day 1.		Subjects who signed informed consent and were thus enrolled, but were not randomized to study treatment.
All Cause Mortality
	Investigational		Control		Enrolled, Not Randomized
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/22 (4.5%)		0/21 (0%)		0/3 (0%)
Serious Adverse Events
	Investigational		Control		Enrolled, Not Randomized
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/22 (90.9%)		19/21 (90.5%)		0/3 (0%)
Blood and lymphatic system disorders
Anaemia	1/22 (4.5%)	1	0/21 (0%)	0	0/3 (0%)	0
Febrile neutropenia	1/22 (4.5%)	1	0/21 (0%)	0	0/3 (0%)	0
Cardiac disorders
Acute myocardial infarction	1/22 (4.5%)	1	0/21 (0%)	0	0/3 (0%)	0
Pulseless electrical activity	0/22 (0%)	0	1/21 (4.8%)	1	0/3 (0%)	0
Gastrointestinal disorders
Abdominal pain	0/22 (0%)	0	1/21 (4.8%)	1	0/3 (0%)	0
Abdominal pain lower	1/22 (4.5%)	1	0/21 (0%)	0	0/3 (0%)	0
Ascites	0/22 (0%)	0	1/21 (4.8%)	1	0/3 (0%)	0
Constipation	0/22 (0%)	0	1/21 (4.8%)	1	0/3 (0%)	0
Diarrhoea	2/22 (9.1%)	2	1/21 (4.8%)	1	0/3 (0%)	0
Enterocolitis haemorrhagic	1/22 (4.5%)	1	0/21 (0%)	0	0/3 (0%)	0
Gastrointestinal haemorrhage	1/22 (4.5%)	1	0/21 (0%)	0	0/3 (0%)	0
Gastrooesophageal reflux disease	1/22 (4.5%)	1	0/21 (0%)	0	0/3 (0%)	0
Ileus	0/22 (0%)	0	1/21 (4.8%)	1	0/3 (0%)	0
Impaired gastric emptying	0/22 (0%)	0	2/21 (9.5%)	2	0/3 (0%)	0
Nausea	2/22 (9.1%)	2	1/21 (4.8%)	1	0/3 (0%)	0
Oesophagitis	0/22 (0%)	0	1/21 (4.8%)	1	0/3 (0%)	0
Pancreatitis	1/22 (4.5%)	1	0/21 (0%)	0	0/3 (0%)	0
Small intestinal obstruction	1/22 (4.5%)	1	0/21 (0%)	0	0/3 (0%)	0
Volvulus of small bowel	1/22 (4.5%)	1	0/21 (0%)	0	0/3 (0%)	0
Vomiting	2/22 (9.1%)	2	1/21 (4.8%)	1	0/3 (0%)	0
General disorders
Pyrexia	2/22 (9.1%)	2	1/21 (4.8%)	1	0/3 (0%)	0
Immune system disorders
Kidney transplant rejection	1/22 (4.5%)	1	3/21 (14.3%)	3	0/3 (0%)	0
Pancreas transplant rejection	7/22 (31.8%)	7	3/21 (14.3%)	4	0/3 (0%)	0
Renal and pancreas transplant rejection	2/22 (9.1%)	2	0/21 (0%)	0	0/3 (0%)	0
Infections and infestations
Bacteraemia	1/22 (4.5%)	1	0/21 (0%)	0	0/3 (0%)	0
Cellulitis	1/22 (4.5%)	1	0/21 (0%)	0	0/3 (0%)	0
Clostridial infection	0/22 (0%)	0	1/21 (4.8%)	1	0/3 (0%)	0
Cytomegalovirus viraemia	1/22 (4.5%)	1	0/21 (0%)	0	0/3 (0%)	0
Gangrene	0/22 (0%)	0	1/21 (4.8%)	1	0/3 (0%)	0
Gastroenteritis	0/22 (0%)	0	1/21 (4.8%)	1	0/3 (0%)	0
Haematoma infection	0/22 (0%)	0	1/21 (4.8%)	1	0/3 (0%)	0
Infection	1/22 (4.5%)	1	0/21 (0%)	0	0/3 (0%)	0
Influenza	0/22 (0%)	0	2/21 (9.5%)	2	0/3 (0%)	0
Meningitis viral	0/22 (0%)	0	1/21 (4.8%)	1	0/3 (0%)	0
Oesophageal candidiasis	1/22 (4.5%)	1	0/21 (0%)	0	0/3 (0%)	0
Pancreas infection	1/22 (4.5%)	1	0/21 (0%)	0	0/3 (0%)	0
Pancreatic abscess	1/22 (4.5%)	1	1/21 (4.8%)	1	0/3 (0%)	0
Parvovirus infection	0/22 (0%)	0	1/21 (4.8%)	1	0/3 (0%)	0
Pneumocystis jiroveci pneumonia	0/22 (0%)	0	1/21 (4.8%)	1	0/3 (0%)	0
Pneumonia	1/22 (4.5%)	2	0/21 (0%)	0	0/3 (0%)	0
Pyelonephritis	0/22 (0%)	0	2/21 (9.5%)	2	0/3 (0%)	0
Sepsis	0/22 (0%)	0	1/21 (4.8%)	2	0/3 (0%)	0
Urinary tract infection	3/22 (13.6%)	3	4/21 (19%)	6	0/3 (0%)	0
Urinary tract infection bacterial	0/22 (0%)	0	1/21 (4.8%)	1	0/3 (0%)	0
Urosepsis	2/22 (9.1%)	2	0/21 (0%)	0	0/3 (0%)	0
Viral upper respiratory tract infection	0/22 (0%)	0	1/21 (4.8%)	1	0/3 (0%)	0
Wound infection staphylococcal	0/22 (0%)	0	1/21 (4.8%)	1	0/3 (0%)	0
Injury, poisoning and procedural complications
Anastomotic haemorrhage	1/22 (4.5%)	1	0/21 (0%)	0	0/3 (0%)	0
Chemical burn of skin	0/22 (0%)	0	1/21 (4.8%)	1	0/3 (0%)	0
Contusion	0/22 (0%)	0	1/21 (4.8%)	1	0/3 (0%)	0
Peripancreatic fluid collection	2/22 (9.1%)	2	1/21 (4.8%)	1	0/3 (0%)	0
Post procedural haematoma	2/22 (9.1%)	2	0/21 (0%)	0	0/3 (0%)	0
Renal transplant torsion	1/22 (4.5%)	1	0/21 (0%)	0	0/3 (0%)	0
Tibia fracture	0/22 (0%)	0	1/21 (4.8%)	1	0/3 (0%)	0
Toxicity to various agents	0/22 (0%)	0	1/21 (4.8%)	1	0/3 (0%)	0
Vascular pseudoaneurysm	1/22 (4.5%)	1	0/21 (0%)	0	0/3 (0%)	0
Investigations
Blood creatinine increased	1/22 (4.5%)	1	0/21 (0%)	0	0/3 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/22 (0%)	0	3/21 (14.3%)	3	0/3 (0%)	0
Failure to thrive	1/22 (4.5%)	1	0/21 (0%)	0	0/3 (0%)	0
Nervous system disorders
Diabetic autonomic neuropathy	1/22 (4.5%)	1	0/21 (0%)	0	0/3 (0%)	0
Renal and urinary disorders
Neurogenic bladder	0/22 (0%)	0	1/21 (4.8%)	1	0/3 (0%)	0
Renal tubular necrosis	0/22 (0%)	0	1/21 (4.8%)	1	0/3 (0%)	0
Ureteric stenosis	1/22 (4.5%)	1	0/21 (0%)	0	0/3 (0%)	0
Urinary retention	1/22 (4.5%)	1	0/21 (0%)	0	0/3 (0%)	0
Skin and subcutaneous tissue disorders
Skin ulcer	1/22 (4.5%)	1	0/21 (0%)	0	0/3 (0%)	0
Vascular disorders
Arteriovenous fistula	1/22 (4.5%)	1	0/21 (0%)	0	0/3 (0%)	0
Orthostatic hypotension	1/22 (4.5%)	1	1/21 (4.8%)	1	0/3 (0%)	0
Peripheral ischaemia	1/22 (4.5%)	1	0/21 (0%)	0	0/3 (0%)	0
Other (Not Including Serious) Adverse Events
	Investigational		Control		Enrolled, Not Randomized
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/22 (90.9%)		19/21 (90.5%)		0/3 (0%)
Blood and lymphatic system disorders
Anaemia	6/22 (27.3%)	6	10/21 (47.6%)	11	0/3 (0%)	0
Leukocytosis	0/22 (0%)	0	2/21 (9.5%)	4	0/3 (0%)	0
Leukopenia	6/22 (27.3%)	7	3/21 (14.3%)	6	0/3 (0%)	0
Thrombocytopenia	1/22 (4.5%)	1	5/21 (23.8%)	5	0/3 (0%)	0
Gastrointestinal disorders
Gastrointestinal haemorrhage	0/22 (0%)	0	2/21 (9.5%)	2	0/3 (0%)	0
Infections and infestations
BK virus infection	8/22 (36.4%)	8	3/21 (14.3%)	3	0/3 (0%)	0
Clostridial infection	2/22 (9.1%)	2	3/21 (14.3%)	4	0/3 (0%)	0
Cytomegalovirus infection	1/22 (4.5%)	1	2/21 (9.5%)	2	0/3 (0%)	0
Cytomegalovirus viraemia	3/22 (13.6%)	6	1/21 (4.8%)	1	0/3 (0%)	0
Oesophageal candidiasis	2/22 (9.1%)	2	1/21 (4.8%)	1	0/3 (0%)	0
Urinary tract infection	8/22 (36.4%)	12	3/21 (14.3%)	4	0/3 (0%)	0
Injury, poisoning and procedural complications
Toxicity to various agents	0/22 (0%)	0	3/21 (14.3%)	3	0/3 (0%)	0
Investigations
Amylase increased	0/22 (0%)	0	2/21 (9.5%)	2	0/3 (0%)	0
Blood creatinine increased	3/22 (13.6%)	4	3/21 (14.3%)	4	0/3 (0%)	0
Lipase increased	1/22 (4.5%)	1	3/21 (14.3%)	3	0/3 (0%)	0
Weight increased	2/22 (9.1%)	2	0/21 (0%)	0	0/3 (0%)	0
Metabolism and nutrition disorders
Dehydration	1/22 (4.5%)	1	2/21 (9.5%)	2	0/3 (0%)	0
Hyperkalaemia	3/22 (13.6%)	3	5/21 (23.8%)	6	0/3 (0%)	0
Hypoalbuminaemia	1/22 (4.5%)	2	2/21 (9.5%)	2	0/3 (0%)	0
Hypokalaemia	1/22 (4.5%)	1	2/21 (9.5%)	2	0/3 (0%)	0
Renal and urinary disorders
Renal failure acute	2/22 (9.1%)	2	3/21 (14.3%)	3	0/3 (0%)	0
Urinary retention	0/22 (0%)	0	2/21 (9.5%)	2	0/3 (0%)	0
Skin and subcutaneous tissue disorders
Skin ulcer	2/22 (9.1%)	2	0/21 (0%)	0	0/3 (0%)	0
Vascular disorders
Hypotension	2/22 (9.1%)	3	2/21 (9.5%)	3	0/3 (0%)	0

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.