Clinical trial NCT01790594: Optimization of NULOJIX® Usage Towards Minimizing CNI Exposure in Simultaneous Pancreas and Kidney Transplantation
Official title: Optimization of NULOJIX® (Belatacept) Usage as a Means of Minimizing CNI Exposure in Simultaneous Pancreas and Kidney Transplantation (CTOT-15)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Simultaneous Kidney and Pancreas Transplantation
Keywords: transplantation
kidney
pancreas
immunosuppression
calcineurin inhibitor (CNI)
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Clinical Trials in Organ Transplantation
name: Rho Federal Systems Division, Inc.
name: Bristol-Myers Squibb
First posted: 2013-02-13
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Mean Estimated Glomerular Filtration Rate (eGFR) Calculated for Each Treatment Group Using the CKD-EPI Equation at Wk 52 Post-Transplant
timeFrame: Week 52 Post-Transplant
Secondary outcomes:
measure: Count of Participants With eGFR < 60 mL/Min/1.73 m^2 Measured by CKD-EPI at Wk 52 Post-Transplant
timeFrame: Week 52 Post-Transplant
measure: Count of Participants by CKD Stage at Wk 52 Post-Transplant
timeFrame: Week 52 Post-Transplant
measure: Count of Participants With Defined CKD Stage 4 or 5 at Wk 52 Post-Transplant
timeFrame: Week 52 Post-Transplant
measure: Mean Calculated eGFR Using MDRD 4 Variable Model at Wk 52 Post-Transplant
timeFrame: Week 52 Post-Transplant
measure: The Slope of eGFR by CKD-EPI Over Time Based on Serum Creatinine Post-Transplant
timeFrame: Day 28 through Week 52 Post-Transplant
measure: Count of Participants With Successful Discontinuation of Tacrolimus in Recipients Randomized to the Investigational Arm
timeFrame: Week 40 through week 48 Post-Transplant
measure: Count of Participants With Delayed Graft Function at Wk 52 Post-Transplant
timeFrame: Transplant through Week 52 Post-Transplant
measure: Count of Participants With Full Pancreatic Graft Function (Insulin Independent) at Wk 52 Post-Transplant
timeFrame: Week 52 Post-Transplant
measure: Count of Participants With Evidence of Partial Pancreatic Graft Function at Week 52 Post-Transplant
timeFrame: Week 52 Post-Transplant
measure: Count of Participants With Evidence of Pancreatic Loss at Week 52 Post-Transplant
timeFrame: Week 52 Post-Transplant
measure: HbA1c at Baseline (Pre-Transplant) Through Wk 52 Post-Transplant
timeFrame: Baseline (Pre-Transplant) and Days 28, 84, and Weeks 28, 36, and 52
measure: Fasting Blood Sugar (FBS) From Baseline (Pre-Transplant) Through Wk 52 Post-Transplant
timeFrame: Baseline (Pre-Transplant) and Days 28, 84, and Weeks 28, 36, and 52
measure: Standardized Blood Pressure Measurement From Baseline (Pre-Transplant) Through Wk 52 Post-Transplant
timeFrame: Baseline (Pre-Transplant) and Days 28, 84, and Weeks 28, 36, and 52
measure: Count of Participants With Use of Anti-hypertensive Medication From Baseline (Pre-Transplant) Through Wk 52 Post-Transplant
timeFrame: Baseline (Pre-Transplant) and Days 28, 84, and Weeks 28, 36, and 52
measure: Fasting Lipid Profile at Baseline (Pre-Transplant)
timeFrame: Baseline (Pre-Transplant)
measure: Fasting Lipid Profile at Wk 28 Post-Transplant
timeFrame: Week 28 Post-Transplant
measure: Lipid Profile at Wk 52 Post-Transplant
timeFrame: Week 52 Post-Transplant
measure: Count of Participants With Use of Lipid Lowering Medications at Baseline, Wk 28 and Wk 52 Post-Transplant
timeFrame: Baseline (Pre-Transplant), Week 28, and Week 52
measure: Count of Participants With Acute Rejection (AR) of Kidney or Pancreatic Transplant During the First 52 Wks Post-Transplant
timeFrame: Transplant through Week 52
measure: Severity Grade of First Biopsy-Proven Acute Rejection (AR) During the First 52 Weeks Post-Transplant
timeFrame: Transplant through Week 52
measure: Count of Participants With Biopsy-Proven Humoral Rejection During the First 52 Weeks Post-Transplant
timeFrame: Transplant through Week 52
measure: Count of Participants With De Novo Anti-Donor Antibodies or Anti-Human Leukocyte Antigen (HLA) Antibodies During the First 52 Weeks Post-Transplant
timeFrame: Transplant through Week 52
measure: Type of Treatment(s) Participants Received for Biopsy-Proven Renal Allograft Rejection During the First 52 Weeks Post-Transplant
timeFrame: Transplant through Week 52
measure: Type of Treatment(s) Participants Received for Biopsy-Proven Pancreatic Allograft Rejection During the First 52 Weeks Post-Transplant
timeFrame: Transplant through Week 52
measure: Count of Participants With Event of Death, Graft Loss, or Undetectable C-peptide
timeFrame: Transplant through Week 52 Post-Transplant
measure: Count of Participants With the Occurrence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From Enrollment (Pre-Transplant) to Week 52 Post-Transplant
measure: Count of Participants With an Infectious Disease Serious Adverse Event(s) Requiring Hospitalization or Systemic Therapy
timeFrame: Transplant through Week 52 Post-Transplant
measure: Count of Participant Diagnosed With BK Polyoma Virus (BKV) and Cytomegalovirus (CMV) Viremia As Adverse Events
timeFrame: Transplant through Week 52 Post-Transplant
measure: Count of Participants Diagnosed With Epstein-Barr Virus (EBV) Infection as an Adverse Event
timeFrame: Transplant through Week 52 Post-Transplant
measure: Count of Participants Diagnosed With Malignancy as an Adverse Event
timeFrame: Transplant through Week 52 Post-Transplant
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: San Francisco
country: United States
facility: University of California San Francisco Medical Center
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University Hospital
state: Indiana
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: Emory University
name: Kenneth Newell, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.