Clinical trial NCT01856257: Open-Label Phase 2 Trial of a Steroid-Free, CNI-Free, Belatacept-Based Immunosuppressive Regimen
Official title: Steroid and Tacrolimus Avoidance Using NULOJIX® (Belatacept) in Renal Transplantation (CTOT-16)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Primary Renal Allograft Candidate
Kidney Transplantation
Keywords: Kidney Transplantation
Transplantation
NULOJIX
belatacept
chronic immunosuppression
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Clinical Trials in Organ Transplantation
First posted: 2013-05-17
Enrollment: 71
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 primary objective is to evaluate a NULOJIX® (belatacept) based regimens as a means of improving long-term graft function without increasing the risks of immunologic graft injury by avoiding both calcineurin inhibitors (CNIs) and corticosteroids.

Detailed description: Taking standard anti-rejection medications for a long time can cause serious side effects, including kidney damage. 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 receive a kidney transplant must take these anti-rejection medications for the rest of their lives, or for as long as the kidney continues to work.

The purpose of this study is to determine if NULOJIX® (belatacept), will minimize serious long term side effects seen with anti-rejection medications while still protecting the transplanted kidney from damage. The researchers also want to learn more about the safety of this treatment and the long term health of the transplanted 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 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;
* Participants with reproductive potential must agree to use an appropriate method(s) of birth control as outlined in the CellCept® , Myfortic® or generic package labeling during participation in the study and for 4 months following completion of the study;
* No donor specific antibodies prior to transplant that are considered to be of clinical significance by the site investigator;
* Negative crossmatch or Panel Reactive Antibodies (PRA) of 0% on historic and current sera, as determined by each participating study center;
* A documented negative tuberculosis (TB) test within the 6 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;
* Epstein-Barr Virus (EBV) seronegative (or unknown) recipients;
* Active infection including hepatitis B, hepatitis C, or human Immunodeficiency Virus (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;
* Histocompatibility antigen (HLA) identical living donors;
* Individuals at significant risk of early recurrence of the primary renal disease including focal segmental glomerulosclerosis (FSGS) and membranoproliferative glomerulonephritis (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;
* Known history of thrombotic events or risk factors, including any of the following:

  * Factor V Leiden, elevated homocysteine, positive lupus anticoagulant, elevated anticardiolipin antibody, heparin-induced thrombocytopenia,
  * A family history of a heritable thrombotic condition,
  * Recurrent deep vein thrombosis (DVT) or pulmonary emboli (PE),
  * Unexplained stillborn infant or recurrent spontaneous abortion or other congenital or acquired thrombotic disorder.

At the discretion of the investigator, a history of thrombosis of a dialysis access graft, fistula, or indwelling catheter/device may not be considered an exclusion criterion.

* 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;
* Blood type A2 and A2B donors into blood type B recipients.

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
Secondary outcomes:
measure: Count of Participants With Biopsy Proven Acute Rejection By Wk 52 Post-Transplant
timeFrame: Transplantation through Week 52
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
measure: Count of Participants by CKD Stage at Wk 52
timeFrame: Week 52
measure: Count of Participants With Defined CKD Stage 4 or 5 at Wk 52 Post-Transplant
timeFrame: Week 52
measure: Mean Calculated eGFR Using MDRD 4 Variable Model at Wk 52 Post-Transplant
timeFrame: Week 52
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 Delayed Graft Function at Wk 52 Post-Transplant
timeFrame: Transplantation through Week 52
measure: Count of Participants With Acute Cellular Rejection Grade ≥ IA Defined by Banff 2007 Criteria By Wk 52 Post-Transplant
timeFrame: Transplantation through Week 52
measure: Count of Participants by Severity of First Acute Cellular Rejection by Wk 52 Post-Transplant
timeFrame: Transplantation through Week 52
measure: Count of Participants With Antibody Mediated Rejection by Wk 52 Post-Transplant
timeFrame: Transplantation through Week 52
measure: Type of Rejection Classified by Pathologist - For Cause Kidney Biopsies
timeFrame: Transplantation through Week 52
measure: Type of Treatment for Detected Graft Rejection
timeFrame: Transplantation through Week 52
measure: Count of Participants With De Novo Anti-Donor Histocompatibility Antigen (HLA) Antibodies at Wk 52 Post-Transplant
timeFrame: Week 52
measure: Count of Participants With Either New Onset Diabetes After Transplant (NODAT) or Impaired Fasting Glucose (IFG) at Week 52 Post-Transplant -Based on Criteria Specified by the ADA and WHO
timeFrame: Transplantation through Week 52
measure: Count of Participants With Treated Diabetes Between Day 14 and Wk 52 Post-Transplant
timeFrame: Day 14 through week 52
measure: Hemoglobin A1c (HbA1c) Measurements Over Time
timeFrame: Baseline (Pre-Transplant) and Days 28 and -84, and Weeks 28, -36, and -52 Post-Transplant
measure: Standardized Blood Pressure Measurement at Wk 52 Post-Transplant
timeFrame: Week 52
measure: Count of Participants With Use of Anti-hypertensive Medication at Wk 52 Post-Transplant
timeFrame: Week 52
measure: Fasting Lipid Profile at Baseline (Pre-Transplant)
timeFrame: Baseline
measure: Fasting Lipid Profile at Wk 28 Post-Transplant
timeFrame: Week 28
measure: Fasting Lipid Profile at Wk 52 Post-Transplant
timeFrame: Week 52
measure: Count of Participants With Use of Lipid Lowering Medications at Baseline and Wk 28 and Wk 52 Post-Transplant
timeFrame: Baseline (Pre-Transplant), Week 28, and Week 52
measure: Total Daily Prescribed Pill Count
timeFrame: Day 28, Day 84, Week 28, Week 36, and Week 52
measure: Count of Participant Deaths or Graft Loss by Wk 52 Post-Transplant
timeFrame: Transplantation through Week 52
measure: Count of Participants With Graft Rejection by Wk 52 Post-Transplant
timeFrame: Transplantation through Week 52
measure: Count of Participants Experiencing ≥ 1 Adverse Event (AEs) or Serious Adverse Events (SAEs) by Wk 52
timeFrame: Enrollment through Week 52
measure: Count of Participants With Infections Requiring Hospitalization or Systemic Therapy by Wk 52 Post-Transplant
timeFrame: Transplantation through Week 52
measure: Count of Participants With BK Polyoma Virus (BKV) and Cytomegalovirus (CMV) Viremia (Local Center Monitoring) as Adverse Events by Wk 52 Post-Transplant
timeFrame: Transplantation through Week 52
measure: Count of Participants With Epstein-Barr Virus (EBV) Infection as Reported on the Case Report Form as Adverse Events
timeFrame: Transplantation through Week 52
measure: Count of Participants With Fever > 39 Degrees Celsius and Blood Pressure < 90 mmHg Within 24 Hours of Onset of Transplant Procedure
timeFrame: Within 24 Hours of transplant procedure
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
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
Study officials:
affiliation: Emory University
name: Kenneth Newell, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alabama at Birmingham
name: Roslyn B. Mannon, M.D.
role: STUDY_CHAIR
References:
citation: Mannon RB, Armstrong B, Stock PG, Mehta AK, Farris AB, Watson N, Morrison Y, Sarwal M, Sigdel T, Bridges N, Robien M, Newell KA, Larsen CP. Avoidance of CNI and steroids using belatacept-Results of the Clinical Trials in Organ Transplantation 16 trial. Am J Transplant. 2020 Dec;20(12):3599-3608. doi: 10.1111/ajt.16152. Epub 2020 Jul 13.