Study Comparing the Safety and Efficacy of Belatacept With That of Cyclosporine in Patients With a Transplanted Kidney

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 2

Conditions: Kidney Transplantation; Graft Rejection; Renal Transplantation

Treatments: Drug: Cyclosporine; Drug: Mycophenolate mofetil (MMF); Drug: Corticosteroids; Drug: Belatacept

Study type: Interventional

Funder types: Industry

Identifiers

NCT00035555

IM103-100

Details and patient eligibility

About

The purpose of this study is to determine whether treatment with Belatacept (BMS-224818) is as efficacious as treatment with cyclosporine at preventing acute rejection and with a superior safety/tolerability profile (better kidney function and blood pressure, fewer lipid problems, less diabetes mellitus).

Enrollment: 230 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key inclusion criteria

• Recipients of first kidney transplant

Key exclusion criteria

• Those at high risk for acute allograft rejection, including those who receive a second or more renal transplant, those with a history of panel reactive antibody levels >20%, and those considered by investigators to be at relatively higher risk for acute rejection
• Human leukocyte antigen-identical donor-recipient pairs
• Cold ischemia time >36 hours (donor kidney)
• Participants who are positive for hepatitis C antibody, on polymerase chain reaction, for hepatitis B surface antigen, and for human immunodeficiency virus
• A positive purified protein derivative tuberculosis test (test performed within 1 year of enrollment), unless previously vaccinated with Bacille-Calmette-Guérin or those who had a history of adequate chemoprophylaxis
• Any active infection that would normally exclude transplantation
• Recipients of multiple organ transplants
• Donor age >60 or <6 years or donors whose hearts were not beating
• Recipients with underlying renal disease of (due to risk of rapid disease recurrence in the allograft): focal segmental glomerulosclerosis, Type I or II membranoproliferative glomerulonephritis, or hemolytic uremic syndrome/ thrombotic thrombocytopenic purpura
• A positive T-cell lymphocytoxic crossmatch using donor lymphocytes and recipient serum
• A history of true allergy to intravenous iodinated roentgenographic contrast agents
• Participants with life expectancy severely limited by disease state or other underlying medical condition
• A history of cancer (other than nonmelanoma skin cell cancers cured by local resection) within the last 5 years
• Mammogram film with any clinically significant abnormality requiring further investigation or biopsies
• History of substance abuse (drug or alcohol) or psychotic disorders that were not compatible with adequate study follow-up
• A currently functioning, nonrenal transplant
• Previous treatment with basiliximab for any reason
• Active peptic ulcer disease, chronic diarrhea, or gastrointestinal malabsorption
• Those who had used any investigational drug within 30 days before the Day 1 visit.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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230 participants in 3 patient groups

Belatacept: More intensive (MI) regimen

Experimental group

Description:

The MI regimen was designed to achieve projected serum trough concentrations of belatacept of approximately 20 μg/mL through Day 99, and approximately 5 μg/mL through Day 183 (10 mg/kg on Days 1, 5, 15, 29, 43, 57, 71, 85, 113, 141, and 169). After Day 169, patients were reallocated and dosed to achieve projected trough serum concentrations of approximately 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 197). Those patients who received belatacept every 8 weeks received placebo infusions on scheduled treatment dates between infusions of active drug to maintain the blind between treatment regimens. Patients initially received mycophenolate mofetil (MMF), 2 g/d orally, unless the investigator chose to administer ≥1 doses intravenously The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the patient was able to tolerate medications by mouth. Corticosteroids given daily.

Treatment:

Drug: Belatacept

Drug: Mycophenolate mofetil (MMF)

Drug: Corticosteroids

Belatacept: Less intensive (LI) regimen

Experimental group

Description:

The LI regimen was designed to achieve projected trough serum concentrations of belatacept of approximately 20 μg/mL through Day 29, and approximately 5 μg/mL through Day 99 (10 mg/kg on Days 1, 15, 29, 57 and 85). After Day 85, these subjects were reallocated and dosed to achieve projected trough serum concentrations of either approximately 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 113). Participants initially received mycophenolate mofetil (MMF), 2 g/d orally, unless the investigator chose to administer ≥1 doses intravenously The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. Corticosteroids given daily.

Treatment:

Drug: Belatacept

Drug: Mycophenolate mofetil (MMF)

Drug: Corticosteroids

Cyclosporine regimen

Experimental group

Description:

The initial daily dose was 7±3 mg/kg. Subsequent doses were adjusted to maintain a predefined range of serum concentrations: 1st month, target level 150-400 ng/mL; after 1st month, target level of 150-300 ng/mL. Participants initially received mycophenolate mofetil (MMF), 2 g/d orally, unless the investigator chose to administer ≥1 doses intravenously The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth. Corticosteroids given daily.

Treatment:

Drug: Cyclosporine

Drug: Mycophenolate mofetil (MMF)

Drug: Corticosteroids