Belatacept 3 Month Post Transplant Conversion Study

NCT02213068 | Completed Phase 4 Results

• 1 other identifier: STU00085274
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being done to investigate the impact of changing immunosuppressive medications from tacrolimus (Prograf®) to belatacept (Nulojix®) between three (3) and six (6) months after kidney transplantation. The immune system is the body's defense against infection and other disease. After transplantation, the body sees the new organ as "foreign" and tries to destroy or "reject" it. Immunosuppressive medications help to prevent the immune system from attacking the transplanted organ. The primary purpose of this research study is to evaluate the effects of three (3) different immunosuppressive treatments on rejection in post-transplant kidney recipients. This study will test whether switching from tacrolimus to belatacept will improve long-term kidney function. Three of the immunosuppressants used in this study- mycophenolic acid (MPA), mycophenolate mofetil (MMF) and tacrolimus- are medications approved by the United States Food and Drug Administration (FDA) to be used after transplant. All of these medications have been routinely used in kidney recipients here at Northwestern University. Belatacept (the "study drug") has been approved by the FDA for use at the time of transplant. However, the use of belatacept in this study is considered investigational as it has not been FDA approved for use beginning at 3 months after transplant. This study will involve 51 adult kidney transplant recipients at Northwestern.

Conditions

Transplant; Failure, Kidney; EBV

Keywords

Kidney; Renal; Transplant; EBV; Immunosuppressants; Belatacept

Outcome Measures

Primary Outcomes (4)

• Change in eGFR (MDRD) at 2 Years Post-transplant Compared to Baseline at Month 3 (Conversion)

  To assess change in renal function by calculated (MDRD) GFR of adult EBV seropositive renal transplant recipients of living or standard criteria donors converted from Tacrolimus to Belatacept or low dose Tacrolimus with Belatacept at three months post-operatively compared to renal transplant recipients randomized to remain on standard dose Tacrolimus and MPA for maintenance therapy at 2 years post-transplantation

  2 years

• Acute Rejection

  Number of Participants with Acute Rejection (AR). AR is defined as allograft dysfunctions in the setting of recipient immune system engaging an allo-response against the kidney transplant.

  2 years

• Graft Survival

  Number of Subjects with a functioning Graft

  2 years

• Patient Survival

  Number of Subjects alive at the end of 24 months

  2 years

Study Arms (3)

belatacept + MPA

EXPERIMENTAL

subjects continue MPA per SOC, receive bimonthly infusions of belatacept while gradually reducing and then discontinuing tacrolimus: Belatacept: 5 mg/kg IV on Day 1, 15, 29, 43, and 57 post-conversion, then monthly thereafter. Tacrolimus tapered over one month as follows: Days 1- 14: SOC administration Day 15 (\~ 2 weeks into study): 40-60% of the previous dose Day 21 (\~ 3 weeks into study): 20-30% of the previous dose Day 30 (about 1 month): discontinue MPA: administered according to SOC

Drug: belatacept; Drug: MPA

belatacept + Low-Dose Tac

ACTIVE COMPARATOR

Belatacept: 5 mg/kg IV on Day 1, 15, 29, 43, and 57 post-conversion, then monthly thereafter. Tacrolimus tapered over one month as follows: Days 1- 14: SOC administration Day 15 (\~ 2 weeks into study): 10% of the previous dose Day 21 (\~ 3 weeks into study): 20% of the previous dose Day 30 (\~ 1 month into study): 20% of the previous dose Target trough level ≤ 5 mg per ml of tacrolimus thereafter.

Drug: belatacept; Drug: Tacrolimus

Tacrolimus + MPA standard treatment regimen

OTHER

Standard of Care treatment regimen: Tacrolimus: administered orally twice daily (BID) The total initial dose of Tacrolimus is given at 0.1 mg/kg in two divided doses to achieve a stable 12-hour trough level of 8 - 12 ng/mL on Days 1 through 30, with dose reduction to achieve a 12-hour trough target of 5 - 10 ng/mL thereafter. MPA: dosed orally per package insert beginning on the day of transplantation. Methylprednisolone as sodium succinate is administered as 500 mg IV, 250 mg IV, 125 mg IV, on Days 0, 1, and 2 without corticosteroid taper. MPA dose adjustments for gastrointestinal side effects or leukopenia will be made at the discretion of the investigator.

Drug: Tacrolimus; Drug: MPA

Interventions

belatacept DRUG

Please reference Arm description for belatacept + MPA and Arm description for Arm belatacept + Low-Dose Tac for details on this intervention

Also known as: Belatacept (Nulojix®)

belatacept + Low-Dose Tac; belatacept + MPA

Tacrolimus DRUG

Please see Arm Descriptions for both Standard of Care Arm Tacrolimus + MPA standard treatment regimen and belatacept + Low-Dose Tac for details on this intervention

Also known as: Tacrolimus (Prograf®)

Tacrolimus + MPA standard treatment regimen; belatacept + Low-Dose Tac

MPA DRUG

Please see Arm Descriptions for both Standard of Care Arm Tacrolimus + MPA standard treatment regimen and belatacept + MPA for details on this intervention

Also known as: Mycophenolic Acid (MPA) (Myfortic®)

Tacrolimus + MPA standard treatment regimen; belatacept + MPA

Eligibility Criteria

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

You may qualify if:

• Adult ≥ 18 years of age
• Male or Female
• EBV seropositive
• Recipient of renal transplant from living or deceased donor

You may not qualify if:

• Recipients with EBV serostatus negative or unknown
• History of acute rejection (AR) within 3 months prior to randomization
• History of positive donor specific antibodies (DSA)
• History of antibody mediated rejection
• Positive T-cell lymphocytotoxic cross match
• Proteinuria \>1 g/day or \> 0.5 g/day if diabetic
• Rejection on 3 month post-transplant screening biopsy
• BK nephropathy at 3 months post-transplant screening biopsy
• Positive pregnancy test at the time of randomization in female of child bearing potential
• History of previous transplant

Sponsors & Collaborators

• Lorenzo Gallon: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Northwestern University, The Comprehensive Transplant Center

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Interventions

Abatacept; Tacrolimus; Mycophenolic Acid

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

Results Point of Contact

• Title: Lorenzo Gallon, MD
• Organization: Northwestern University

l-gallon@northwestern.edu

312-695-4457

Study Officials

• Lorenzo Gallon, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• 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: SPONSOR INVESTIGATOR
• PI Title: Associate Professor, Northwestern University, Feinberg School of Medicine

Study Record Dates

• First Submitted: August 7, 2014
• First Posted: August 11, 2014
• Study Start: July 1, 2014
• Primary Completion: September 1, 2020
• Study Completion: September 1, 2020
• Last Updated: February 8, 2023
• Results First Posted: September 8, 2021

Record last verified: 2023-01

Locations

US (1)