Belatacept Compared to Tacrolimus in Deceased Donor Renal Transplant Recipients

NCT02152345 | Completed Phase 4 Results DMC

• 1 other identifier: AAAL7011
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to find out whether treatment to prevent kidney rejection with belatacept in presence of Thymoglobulin induction and withdrawal of steroids will result in less delayed graft function or "sleepy kidney" after transplant than that seen in patients who get tacrolimus as their main drug to prevent rejection instead of belatacept. The investigators will also look at whether patients who get belatacept have the same, lesser or more problems that those who get tacrolimus.

Conditions

Implant or Graft; Rejection

Keywords

kidney; renal; transplant; belatacept; delayed graft function; thymoglobulin; tacrolimus; kidney function; immunosuppression; NGAL

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Delayed Graft Function (DGF)

  To assess whether treatment with Thymoglobulin induction and belatacept based maintenance immunosuppression would reduce delayed graft function (DGF) rates among recipients of deceased donor renal transplants as measured by clinical findings and NGAL marker, as specified below and defined by others. This will be compared to the incidence of DGF in patients treated with a Tacrolimus based regimen. Patients who require hemodialysis in the first 7 days after transplantation and/or patients whose serum creatinine decreases \<10% during 3 consecutive days after the transplant will be considered to have DGF in the absence of other confounding factors such as obstruction or infection. NGAL will be used as a verification marker of DGF.

  Up to 3 months post-transplantation

Secondary Outcomes (3)

• Percentage of Participants With Allograft Survival

  Up to 1 year post-transplantation

• Number of Participants With an Allograft Rejection Episode

  Up to 1 year post-transplantation

• Estimated Glomerular Filtration Rate (eGFR)

  Up to 1 year post-transplantation

Study Arms (2)

Belatacept Immunosuppression

EXPERIMENTAL

Renal transplant recipients will receive steroids (Methylprednisolone), rATG, Belatacept and Mycophenolate. Subjects will be followed for primary endpoint to Day 7 and Month 3 after transplantation and secondary endpoints of kidney function and patient and graft survival up to month 36 after transplantation.

Drug: Belatacept; Drug: Mycophenolate; Drug: rATG; Drug: Methylprednisolone; Procedure: Renal transplant

Standard Immunosuppression (Tacrolimus)

ACTIVE COMPARATOR

Renal transplant recipients will receive standard immunosuppressive therapy, including steroids (Methylprednisolone), rATG, Tacrolimus and Mycophenolate. Subjects will be followed for primary endpoint to Day 7 and Month 3 after transplantation and secondary endpoints of kidney function and patient and graft survival up to month 36 after transplantation.

Drug: Tacrolimus; Drug: Mycophenolate; Drug: rATG; Drug: Methylprednisolone; Procedure: Renal transplant

Interventions

Belatacept DRUG

Belatacept 10 mg/kg will be administered in the operating room approximately 1 hour prior to kidney allograft reperfusion (Day 0). It will then be administered at 10 mg/kg on the following post-transplantation days: Day 5, 14, 30, 56, and 84. Belatacept 5 mg/kg will be administered every four weeks thereafter until end of study.

Also known as: Nulojix

Belatacept Immunosuppression

Tacrolimus DRUG

Tacrolimus 0.05 mg/kg by mouth every 12 hours will be on Day 0 after transplantation. It will then be administered at 8-12 ng/mL on the following post-transplantation days: Day 3-90; at 8-10 ng/mL Day 91-180. Tacrolimus 6 - 8 ng/mL will be administered daily thereafter until end of study. (standard of care)

Also known as: Prograf

Standard Immunosuppression (Tacrolimus)

Mycophenolate DRUG

An immunosuppressive agent used with other medicines to lower the body's natural immunity in patients who receive kidney transplants. 720 mg by mouth every 12 hours (Day 0)(1080 mg AA). (standard of care)

Also known as: Myfortic

Belatacept Immunosuppression; Standard Immunosuppression (Tacrolimus)

rATG DRUG

1.5 mg/kg IV daily on Day 0-3. (standard of care)

Also known as: induction with rabbit anti-thymocyte globulin

Belatacept Immunosuppression; Standard Immunosuppression (Tacrolimus)

Methylprednisolone DRUG

500 mg (Day 0), 250mg (Day 1), 125mg (Day 2), 75 mg (Day 3) IV administered from Day 0-3. (standard of care)

Also known as: Medrol

Belatacept Immunosuppression; Standard Immunosuppression (Tacrolimus)

Renal transplant PROCEDURE

Standard organ transplant of a kidney into a patient with end-stage renal disease.

Also known as: Kidney transplant

Belatacept Immunosuppression; Standard Immunosuppression (Tacrolimus)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have known Epstein-Barr virus (EBV) serostatus, and that status must be positive
• Adult patients ≥18 years of age, receiving a deceased donor kidney transplant at Columbia University Medical Center (CUMC)
• Patients with a PRA ≤ of 50
• Primary or re-transplant candidates (no more than 5th renal transplant)
• Deceased donor renal transplant recipients
• Candidates eligible for rATG induction
• Patients fully consented prior to transplantation
• Women of reproductive age who are willing to delay pregnancy for the duration of the study and use appropriate recommended contraception

You may not qualify if:

• Seronegative or unknown EBV serologic status (due to the risk of post-transplant lymphoproliferative disorder, PTLD), predominantly involving the central nervous system.
• Patients with tuberculosis who have not been treated for latent infection.
• Scheduled to undergo multi-organ transplantation
• Recipients of previous non-renal organ transplant
• Patient receiving 5th renal transplant at the time of screening.
• Patients with a PRA \> 50
• Recipient is pre-emptive status.
• Recipient with positive flow crossmatch.
• History or known HIV
• Known hypersensitivity or contra-indications to Belatacept, Tacrolimus, Mycophenolate mofetil (cellcept), or mycophenolic acid
• Use of an investigational drug in the past 30 days before day of surgery
• Enrolled in a clinical trial other than the current
• Lactating or pregnant women
• Donor specific antibodies (DSA) identified at the time of transplantation
• ABO incompatible renal transplant

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Rejection, Psychology; Delayed Graft Function

Interventions

Abatacept; Tacrolimus; Mycophenolic Acid; Neoadjuvant Therapy; Antilymphocyte Serum; Methylprednisolone; Kidney Transplantation

Condition Hierarchy (Ancestors)

Social Behavior; Behavior; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Combined Modality Therapy; Therapeutics; Immune Sera; Immunoproteins; Biological Products; Complex Mixtures; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Renal Replacement Therapy; Organ Transplantation; Transplantation; Surgical Procedures, Operative; Urologic Surgical Procedures; Urogenital Surgical Procedures

Results Point of Contact

• Title: Dr. Mark A. Hardy
• Organization: Columbia University Irving Medical Center

mah1@cumc.columbia.edu

(212) 305-5502

Study Officials

• Mark A. Hardy, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Auchincloss Professor of Surgery

Study Record Dates

• First Submitted: May 29, 2014
• First Posted: June 2, 2014
• Study Start: June 1, 2014
• Primary Completion: December 31, 2016
• Study Completion: December 31, 2016
• Last Updated: February 10, 2021
• Results First Posted: September 10, 2019

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)