A Phase II Study of Belatacept (BMS-224818) With a Steroid-free Regimen in Subjects Undergoing Kidney Transplantation

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00455013
First received: March 30, 2007
Last updated: February 28, 2012
Last verified: February 2012
  Purpose

The purpose of this clinical research study is to learn if belatacept (BMS-224818) is expected to show acceptable rates of acute rejection (AR) in steroid-free belatacept-based immunosuppressive regiments compared to a similar steroid-free tacrolimus regimen. The long-term safety and tolerability of belatacept based regimens following long-term administration in subjects who have received a kidney transplant


Condition Intervention Phase
Renal Transplantation
Drug: Thymoglobulin
Drug: Belatacept
Drug: Sirolimus
Drug: Tacrolimus
Drug: Mycophenolate Mofetil (MMF)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open-Label, Multicenter, Parallel-Group Study of Belatacept (BMS-224818)-Based Corticosteroid-Free Regimens in Renal Transplant

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • AR rate in corticosteroid-free belatacept-based regimens [ Time Frame: 6 months post-transplantation ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • AR [ Time Frame: by 6/12 months ] [ Designated as safety issue: Yes ]
  • Death/graft loss [ Time Frame: by 12 months ] [ Designated as safety issue: Yes ]
  • AR/death/graft loss [ Time Frame: by 6 and 12 months ] [ Designated as safety issue: Yes ]
  • Metabolic/cardiovascular (CV) comorbidity [ Time Frame: by 12 months ] [ Designated as safety issue: Yes ]
  • Renal function [ Time Frame: by 12 months ] [ Designated as safety issue: Yes ]
  • Corticosteroid-free subjects [ Time Frame: at 12 months ] [ Designated as safety issue: Yes ]
  • Treatment discontinuation [ Time Frame: by 12 months ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of different corticosteroid-free belatacept-based immunosuppressive regiments in subjects who have received a kidney transplant and completed 12 months of study treatment [ Time Frame: until month 36 ] [ Designated as safety issue: Yes ]

Enrollment: 93
Study Start Date: July 2007
Estimated Study Completion Date: May 2012
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: Thymoglobulin
Induction therapy, IV infusion, All subjects will receive thymoglobulin 1.5-mg/kg i.v. infusion on Days 1 (day of transplant), 2, 3, and 4 (up to a maximum total dose of 6 mg/kg) i.v. infusion over at least 4 hours
Drug: Belatacept
Belatacept arms will receive i.v. belatacept (10 mg/kg) on Days 1 and 5, and then every other week through Month 3 (Weeks 2, 4, 6, 8, 10, and 12), and then every 4 weeks through Month 6 (Weeks 16, 20, and 24). After 6 months, subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial
Other Name: BMS-224818
Drug: Mycophenolate Mofetil (MMF)
Administered orally in a capsule or solution formulation in 2 divided doses on a consistent schedule in relation to time of day and meals. The dose should be 1 g bid; however 1.5 g bid may be administered at the investigator's discretion until completion of the trial
Experimental: B Drug: Thymoglobulin
Induction therapy, IV infusion, All subjects will receive thymoglobulin 1.5-mg/kg i.v. infusion on Days 1 (day of transplant), 2, 3, and 4 (up to a maximum total dose of 6 mg/kg) i.v. infusion over at least 4 hours
Drug: Belatacept
Belatacept arms will receive i.v. belatacept (10 mg/kg) on Days 1 and 5, and then every other week through Month 3 (Weeks 2, 4, 6, 8, 10, and 12), and then every 4 weeks through Month 6 (Weeks 16, 20, and 24). After 6 months, subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial
Other Name: BMS-224818
Drug: Sirolimus
Sirolimus will be initiated at 5 mg/day on Day 1 (day of transplant) and continued through Day 2. The dosing will be adjusted subsequently to keep pre-dose (C0) levels at 7 - 12 ng/mL for the first 6 months, followed by 5 - 10 ng/mL thereafter
C
(IMPs as comparator regimen)
Drug: Thymoglobulin
Induction therapy, IV infusion, All subjects will receive thymoglobulin 1.5-mg/kg i.v. infusion on Days 1 (day of transplant), 2, 3, and 4 (up to a maximum total dose of 6 mg/kg) i.v. infusion over at least 4 hours
Drug: Tacrolimus
The recommended total initial dose of tacrolimus is 0.1 mg/kg/day in two divided doses orally up to and including week 52. Post week 52 subjects assigned to the tacrolimus arm will receive tacrolimus orally in accordance with local practice and the package insert until completion of the trial
Drug: Mycophenolate Mofetil (MMF)
Administered orally in a capsule or solution formulation in 2 divided doses on a consistent schedule in relation to time of day and meals. The dose should be 1 g bid; however 1.5 g bid may be administered at the investigator's discretion until completion of the trial

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Living or deceased donor renal allograft
  • Men and women, 18 to 70 years old
  • Subjects who have received a de novo kidney transplant, who have completed the initial study treatment through Month 12, and are willing to sign informed consent will be eligible to continue into the long term extension phase

Exclusion Criteria:

  • Pregnant or breastfeeding women
  • Epstein Barr Virus (EBV) negative serology
  • First time renal transplant with panel reactive antibody (PRA) ≥ 50% or retransplantation with PRA > 30%
  • Graft loss due to AR
  • Positive T-cell or B-cell crossmatch
  • Recipients/donors with HIV or hepatitis B/C
  • Active tuberculosis (TB)
  • Immunosuppressive therapy within 1 year of enrollment
  • UNOS ECD organs will be excluded
  • Body mass index (BMI) > 35 kg/m²
  • Subjects who have developed any malignancy (other than non-melanoma skin cancer) or other medical condition that, in the investigator's opinion, should not be treated with an experimental immunosuppressive drug like belatacept
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00455013

Locations
United States, California
Ucsf
San Francisco, California, United States, 94143
United States, Colorado
Denver Nephrology, Pc
Denver, Colorado, United States, 80218
University Of Colorado Health Sciences Center
Denver, Colorado, United States, 80262
United States, Georgia
Medical College Of Georgia
Augusta, Georgia, United States, 30912
United States, Illinois
Northwestern University Feinberg School Of Medicine
Chicago, Illinois, United States, 60611
United States, Michigan
Henry Ford Hospital
Detriot, Michigan, United States, 48202
United States, New York
Albany Medical College
Albany, New York, United States, 12208
United States, North Carolina
Carolinas Medical Center
Charlotte, North Carolina, United States, 28203
United States, Ohio
University Of Cincinnati
Cincinnati, Ohio, United States, 45267
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Italy
Local Institution
Bologna, Italy, 40138
Local Institution
Brescia, Italy, 25123
Local Institution
Padova, Italy, 35128
Local Institution
Roma, Italy, 00168
Spain
Local Institution
Barcelona, Spain, 08907
Local Institution
Sevilla, Spain, 41013
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00455013     History of Changes
Other Study ID Numbers: IM103-034
Study First Received: March 30, 2007
Last Updated: February 28, 2012
Health Authority: United States: Food and Drug Administration
Italy: C.E. A.O.S. ORSOLA-MALPIGHI
Spain: Agencia Espanola de Medicamentos y Productos Sanitarios

Keywords provided by Bristol-Myers Squibb:
Kidney transplant

Additional relevant MeSH terms:
Mycophenolate mofetil
Sirolimus
Everolimus
Tacrolimus
Abatacept
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on May 22, 2013