Clinical trial NCT01436305: Optimization of NULOJIX® Usage As A Means of Avoiding CNI and Steroids in Renal Transplantation
Official title: Optimization of NULOJIX® (Belatacept) Usage as a Means of Avoiding CNI and Steroids in Renal Transplantation (CTOT-10)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Kidney Transplantation
Renal Transplantation
Keywords: immunosuppressive (IS) regimens
long-term graft function
CNI (calcineurin Inhibitor )-free IS regimen
CNI (calcineurin Inhibitor ) IS regimen
corticosteroids
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Clinical Trials in Organ Transplantation
First posted: 2011-09-19
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to assess whether a new drug, Nulojix® (belatacept), would minimize serious long term side effects associated with anti-rejection medications while still protecting the new kidney from damage. The researchers also wanted to learn more about the safety of this treatment and long term health of the transplanted kidney.

Detailed description: Dialysis or kidney transplant are the two ways to treat kidney failure. Transplant recipients have to take anti-rejection medications to prevent their immune system (the body's natural defense system against illness) from rejecting their new kidney. Most patients who undergo a kidney transplant must take these anti-rejection medications for the rest of their lives. Taking standard anti-rejection medications for a long time can cause serious side effects, including kidney damage. There would be a benefit to finding new anti-rejection medications that work just as well, but don't damage the kidney.

Eligibility criteria: Inclusion Criteria:

* Male or Female, 18-65 years of age at the time of enrollment;
* Ability to understand and provide written informed consent;
* Candidate for primary renal allograft from either a living or deceased-donor;
* No known contraindications to study therapy using NULOJIX® (belatacept);
* Female participants 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 completion of the study;
* Flow-based PRA within last 12 months (in absence of a sensitizing event) of \< 30% as determined by each participating study center. If the subject experienced a sensitizing event after the PRA test date, then the PRA must be repeated and confirmed \<30%;
* Negative crossmatch or a PRA of 0% on historic and admission sera as determined by each participating study center.
* A documented negative 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 transplant;
* Recipient of previous organ transplant;
* EBV sero-negative (or unknown) recipients;
* Active infection including hepatitis B, hepatitis C, or HIV;
* Individuals who have required treatment with prednisone or other immunosuppressive drugs within 1 year prior to transplant;
* Individuals undergoing transplant using organs from extended criteria donor (ECD) or donation after cardiac death (DCD) donors;
* HLA identical living donors;
* Individuals at significant risk of early recurrence of the primary renal disease including FSGS and MPGN type 2 or any other disease that in the opinion of the investigator is at increased likelihood of recurrence and which may result in rapid decline in renal function;
* 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 Glomerular Filtration Rate (GFR) Calculated for Each Treatment Group Using the CKD-EPI Equation at Wk 52
timeFrame: Week 52
Secondary outcomes:
measure: Count of Participants With Biopsy Proven Acute Rejection at Any Time Post-Transplant
timeFrame: Transplantation through last study visit (up to week 156)
measure: Count of Participants With Estimated Glomerular Filtration Rate (GFR) < 60 mL/Min/1.73 m^2 by CKD EPI
timeFrame: Week 52, Week 104, and Week 156
measure: Count of Participants by Chronic Kidney Disease (CKD) Stage Post-Transplant
timeFrame: Week 52, Week 104, and Week 156
measure: Count of Participants With CKD Stage 4 or 5
timeFrame: Week 52, Week 104, and Week 156
measure: Mean Calculated eGFR Using MDRD 4 Variable Model
timeFrame: Week 52, Week 104, and Week 156
measure: The Slope of eGFR by CKD-EPI Over Time Based on Serum Creatinine
timeFrame: Week 52, Week 104, and Week 156
measure: Count of Participants With Delayed Graft Function Post-Transplant
timeFrame: Any time within the first week post-transplant
measure: An Increase of One or More Grades of CAN/IFTA When Comparing the Implantation and Subsequent Protocol Biopsies
timeFrame: Week 52, Week 104, and Week 156
measure: Count of Participants With CAN/IFTA Grade I, II or III at Any Time Post-transplant
timeFrame: Transplantation through last study visit (up to week 156)
measure: Count of Participants With Acute Cellular Rejection Grade Equal to or Greater Than IA, by the Banff 2007 Criteria
timeFrame: Transplantation through last study visit (up to week 156)
measure: Count of Participants by Severity of First Acute Cellular Rejection by Wk 52
timeFrame: Transplantation through Week 52
measure: Count of Participants With Antibody Mediated Rejection
timeFrame: Transplantation through last study visit (up to week 156)
measure: Type of Treatment of Rejection
timeFrame: Transplantation through last study visit (up to week 156)
measure: Count of Participants With de Novo Anti-donor HLA Antibodies at Wk 52
timeFrame: Week 52
measure: Count of Participants With Either New Onset Diabetes After Transplant (NODAT) or Impaired Fasting Glucose (IFG) at Wk 52 Based on Criteria Specified by the ADA and WHO
timeFrame: Week 52
measure: Count of Participants With Treated Diabetes Between Day 14 and Wk 52
timeFrame: Day 14 to Week 52
measure: HbA1c Measured at Days 28 & 84, and Weeks 24, 36, 52, 72, 104 and 156
timeFrame: Day 28, Day 84, Week 24, Week 36, Week 52, Week 72, Week 104, Week 156
measure: Standardized Blood Pressure Measurement at Wk 52
timeFrame: Week 52
measure: Count of Participants With Use of Anti-hypertensive Medications at Wk 52
timeFrame: Week 52
measure: Fasting Lipid Profile (Total Cholesterol, Non-HDL Cholesterol, LDL, HDL, and Triglyceride) at Baseline and Wks 24, 52, 104 and 156
timeFrame: Baseline, Week 24, Week 52, Week 104, Week 156
measure: Count of Participants With Use of Lipid Lowering Medications at Baseline and Wks 24, 52, 104 and 156
timeFrame: Baseline, Week 24, Week 52, Week 104, Week 156
measure: Total Daily Prescribed Pill Number at Days 28 and 84, and Wks 24, 36, 52, 72, 104 and 156
timeFrame: Day 28, Day 84, Week 24, Week 36, Week 52, Week 72, Week 104, Week 156
measure: Number of Events of Death or Graft Loss
timeFrame: Transplantation through last study visit (up to week 156)
measure: Count of Participants With Rejection
timeFrame: Transplantation through last study visit (up to week 156)
measure: Number of All Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Enrollment through last study visit (up to week 156)
measure: Count of Participants With Infections Requiring Hospitalization or Systemic Therapy Reported as Serious Adverse Events
timeFrame: Transplantation through last study visit (up to week 156)
measure: Count of Participants With BKV and CMV Viremia (Local Center Monitoring) Reported as Adverse Events
timeFrame: Transplantation through last study visit (up to week 156)
measure: Count of Participants With EBV Infection as Reported on the Case Report Form as Adverse Events
timeFrame: Transplantation through last study visit (up to week 156)
measure: Count of Participants With Fever > 39 Degrees Celsius and Blood Pressure < 90mm Hg Within 24 Hours of Onset of Transplant Procedure
timeFrame: 24 hours after transplantation
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
Study officials:
affiliation: Emory University
name: Kenneth Newell, MD, PhD
role: STUDY_CHAIR
affiliation: Emory University
name: Christian P. Larsen, MD, DPhil
role: PRINCIPAL_INVESTIGATOR
References:
citation: Newell KA, Mehta AK, Larsen CP, Stock PG, Farris AB, Mehta SG, Ikle D, Armstrong B, Morrison Y, Bridges N, Robien M, Mannon RB. Lessons Learned: Early Termination of a Randomized Trial of Calcineurin Inhibitor and Corticosteroid Avoidance Using Belatacept. Am J Transplant. 2017 Oct;17(10):2712-2719. doi: 10.1111/ajt.14377. Epub 2017 Jul 3.