Belatacept Therapy for the Failing Renal Allograft

NCT01921218 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: IRB00060470IM103-133
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test the safety and effectiveness of belatacept (Nulojix®) in preventing antibody formation in patients with chronic failing kidney transplants. This study is a randomized study of first-time kidney transplant patients who have worsening kidney function and biopsy proven grade 2 or 3 interstitial fibrosis/tubular atrophy (IF/TA). Patients must be eligible to get a second transplant. They must have completed or be actively undergoing evaluation for re-listing for a second transplant. Patients will be randomized to either convert to belatacept or continue on calcineurin inhibitor-based therapy.

Conditions

Failing Renal Allograft

Keywords

Kidney transplant

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Donor-specific Antibody Formation

  The number of participants in each group with donor-specific antibody formation at 36 months following randomization.

  Month 36

Secondary Outcomes (4)

• Glomerular Filtration Rate (GFR)

  Baseline up to Month 24

• Time to Initiation of Dialysis

  Up to Year 2

• Number of Participants With Anti-human Leukocyte Antigen (HLA) Alloantibodies

  Baseline up to Month 36

• Number of Infectious Complications

  Baseline up to Month 36

Study Arms (2)

Treatment

EXPERIMENTAL

Belatacept (Nulojix) IV

Drug: Belatacept; Drug: Mycophenolate mofetil; Drug: prednisone

Control

ACTIVE COMPARATOR

Calcineurin inhibitor based therapy (cyclosporine or tacrolimus)

Drug: Calcineurin inhibitor therapy; Drug: Mycophenolate mofetil; Drug: prednisone

Interventions

Belatacept DRUG

Belatacept, dosing 10mg/kg- day 0, 2 weeks, 1 month, 2 months, 3 months; subsequent doses 5mg/kg monthly through duration of trial or until retransplantation, whichever is first.

Also known as: Nulojix

Treatment

Calcineurin inhibitor therapy DRUG

Upon enrollment, wean calcineurin inhibitor (CNI) to target tacrolimus trough of 3-5 nanogram/milliliter (ng/ml)or equivalent cyclosporine trough. Upon initiation of hemodialysis, discontinue CNI therapy over 5 days.

Also known as: tacrolimus, cyclosporine

Control

Mycophenolate mofetil DRUG

Continue current dose at enrollment. Upon initiation of dialysis, decrease dose by half, then discontinue 2 weeks later

Also known as: Cellcept

Control; Treatment

prednisone DRUG

Begin steroid withdrawal one month after initiation of dialysis, with monthly reduction in dose by half, with plans to discontinue prednisone by 3 months after initiation of dialysis

Also known as: Deltasone

Control; Treatment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent
• Kidney transplant recipient (human leukocyte antigen (HLA) non-identical donor) who now has impaired renal allograft function with:
• Estimated glomerular filtration rate (GFR) \< 35 with a decline in GFR of \> 10% in the 12 months prior to enrollment and must have biopsy proven grade II or III interstitial fibrosis/tubular atrophy (IF/TA) OR
• Estimated GFR persistently \< 20 ml/min over the 6 month period prior to enrollment absent other causes for graft dysfunction, and deemed to have a failing allograft by the patient's transplant nephrologist
• On a maintenance immunosuppressive regimen that includes calcineurin inhibitor (CNI)(tacrolimus or cyclosporine) or sirolimus and at least
• MMF of a dose of at least 1 gm/day or comparable dose of azathioprine OR
• Prednisone at a dose of at least 5 mg/day
• Men and women, ages 18 to 70, inclusive

You may not qualify if:

• Women of childbearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the last dose of study drug.
• Women who are pregnant or breastfeeding.
• Women with a positive pregnancy test.
• Sexually active fertile men not using effective birth control if their partners are WOCBP.
• Subjects who are Epstein-Barr Virus (EBV) seronegative.
• Subjects with any prior solid organ (e.g., heart, liver, pancreas) or cell (e.g., islet, bone marrow) transplant other than a renal allograft. Exception may be made for recipient of a simultaneous kidney-pancreas transplant who had previously experienced graft loss of the pancreas allograft due to thrombosis or rejection.
• Subjects with presence of donor specific antibody at the time of enrollment
• Subjects who have a recent history (within 1 yr) of biopsy proven acute rejection \> Banff grade Ia
• Subjects who have a living donor identified for re-transplant within 3 months
• Subjects with a history of post-transplant lymphoproliferative disease (PTLD)
• Subjects at risk for tuberculosis (TB)
• Subjects with a history of cancer within the past 3 years, other than non-melanoma skin cancer(s)
• Subjects with a positive BK virus serum polymerase chain reaction (PCR) \> 20,000 copies at the time of enrollment OR history of biopsy-proven BK nephropathy within the year prior to enrollment.
• Subjects with a mammogram that is suspicious for malignancy and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory, or other diagnostic evaluations
• Subjects who have difficult intravenous access or other reasons that would likely preclude the ability to receive long-term intravenous infusions

Sponsors & Collaborators

• Andrew B Adams: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Emory University

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Interventions

Abatacept; Tacrolimus; Cyclosporine; Mycophenolic Acid; Prednisone

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins; Macrolides; Lactones; Organic Chemicals; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Results Point of Contact

• Title: Idelberto R. Badell, MD
• Organization: Emory University

ibadell@emory.edu

404-712-6562

Study Officials

• Andrew B Adams, MD, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Surgery

Study Record Dates

• First Submitted: August 9, 2013
• First Posted: August 13, 2013
• Study Start: August 1, 2013
• Primary Completion: December 12, 2019
• Study Completion: December 12, 2019
• Last Updated: January 26, 2021
• Results First Posted: January 26, 2021

Record last verified: 2021-01

Locations

US (1)