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

• ClinicalTrials.gov Identifier: NCT01790594
• Recruitment Status: Terminated
• First Posted: February 13, 2013
• Results First Posted: December 7, 2017
• Last Update Posted: July 20, 2021
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Clinical Trials in Organ Transplantation; Rho Federal Systems Division, Inc.; Bristol-Myers Squibb
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

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 (Clinical Trial)
• 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: February 2013
• Actual Primary Completion Date: August 2016
• Actual Study Completion Date: August 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 Name: 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 Name: 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 Name: 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 Name: NULOJIX; Drug: methylprednisolone; Other Name: 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 Name: 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 Name: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Transplant through Week 52 ]

    Humoral rejection (i.e., antibody mediated rejection) of:

    1. 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,
    2. 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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

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

Criteria

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

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35294

United States, California

University of California San Francisco Medical Center

San Francisco, California, United States, 94143-0780

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30322

United States, Indiana

Indiana University Hospital

Indianapolis, Indiana, United States, 46202

United States, Wisconsin

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)

Documents provided by National Institute of Allergy and Infectious Diseases (NIAID):

Study Protocol and Statistical Analysis Plan  [PDF] June 28, 2016

Informed Consent Form  [PDF] June 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 of Results:

Stock PG, Mannon RB, Armstrong B, Watson N, Ikle D, Robien MA, Morrison Y, Odorico J, Fridell J, Mehta AK, Newell KA. Challenges of calcineurin inhibitor withdrawal following combined pancreas and kidney transplantation: Results of a prospective, randomized clinical trial. Am J Transplant. 2020 Jun;20(6):1668-1678. doi: 10.1111/ajt.15817. Epub 2020 Mar 8.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT01790594
• Other Study ID Numbers: DAIT CTOT-15; U01AI084150 ( U.S. NIH Grant/Contract ); NIAID CRMS ID#: 20117 ( Other Identifier: DAIT NIAID ); SDY1433 ( Other Identifier: ImmPort )
• First Posted: February 13, 2013
• Results First Posted: December 7, 2017
• Last Update Posted: July 20, 2021
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Data is available in: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
• Supporting Materials: Study Protocol
• Time Frame: On average, data is available within 24 months after database lock for a trial.

Access Criteria

Open access.

Study's:

• Accession ID is SDY1433, and
• Digital Object Identifier (DOI) is : 10.21430/M3CEH2A7ZF

• URL: https://www.immport.org/home

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; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Calcineurin Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antibiotics, Antineoplastic; Antineoplastic Agents; Antibiotics, Antitubercular; Antitubercular Agents; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuroprotective Agents; Protective Agents; Immune Checkpoint Inhibitors; Antineoplastic Agents, Immunological