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

NCT ID: NCT00035555

Last Updated: 2014-01-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 230 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-03-31
• Study Completion Date: 2012-07-31

Brief Summary

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).

Conditions

Graft Rejection; Kidney Transplantation; Renal Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Belatacept: More intensive (MI) regimen

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.

Group Type: EXPERIMENTAL

Belatacept

Intervention Type: DRUG

Solution, intravenous

Mycophenolate mofetil (MMF)

Intervention Type: DRUG

Oral, capsule

Corticosteroids

Intervention Type: DRUG

Corticosteroids given daily, orally or intravenously (IV). Day of transplant (Day 1): methylprednisolone, 500 mg, given IV on arrival in operating room; Day 2: methylprednisolone, 250 mg, given IV once daily; Day 3: prednisone, 100 mg, given orally once daily; Day 4: prednisone, 50 mg, given orally once daily; Days 5 through 30: prednisone, 25 mg, given orally once daily; Days 31-44: prednisone, 22.5 mg, given orally once daily; Days 45-58: prednisone, 20 mg, given orally once daily

Belatacept: Less intensive (LI) regimen

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.

Group Type: EXPERIMENTAL

Belatacept

Intervention Type: DRUG

Solution, intravenous

Mycophenolate mofetil (MMF)

Intervention Type: DRUG

Oral, capsule

Corticosteroids

Intervention Type: DRUG

Corticosteroids given daily, orally or intravenously (IV). Day of transplant (Day 1): methylprednisolone, 500 mg, given IV on arrival in operating room; Day 2: methylprednisolone, 250 mg, given IV once daily; Day 3: prednisone, 100 mg, given orally once daily; Day 4: prednisone, 50 mg, given orally once daily; Days 5 through 30: prednisone, 25 mg, given orally once daily; Days 31-44: prednisone, 22.5 mg, given orally once daily; Days 45-58: prednisone, 20 mg, given orally once daily

Cyclosporine regimen

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.

Group Type: EXPERIMENTAL

Cyclosporine

Intervention Type: DRUG

Oral, capsule

Mycophenolate mofetil (MMF)

Intervention Type: DRUG

Oral, capsule

Corticosteroids

Intervention Type: DRUG

Corticosteroids given daily, orally or intravenously (IV). Day of transplant (Day 1): methylprednisolone, 500 mg, given IV on arrival in operating room; Day 2: methylprednisolone, 250 mg, given IV once daily; Day 3: prednisone, 100 mg, given orally once daily; Day 4: prednisone, 50 mg, given orally once daily; Days 5 through 30: prednisone, 25 mg, given orally once daily; Days 31-44: prednisone, 22.5 mg, given orally once daily; Days 45-58: prednisone, 20 mg, given orally once daily

Interventions

Belatacept

Solution, intravenous

Intervention Type: DRUG

Cyclosporine

Oral, capsule

Intervention Type: DRUG

Mycophenolate mofetil (MMF)

Oral, capsule

Intervention Type: DRUG

Corticosteroids

Corticosteroids given daily, orally or intravenously (IV). Day of transplant (Day 1): methylprednisolone, 500 mg, given IV on arrival in operating room; Day 2: methylprednisolone, 250 mg, given IV once daily; Day 3: prednisone, 100 mg, given orally once daily; Day 4: prednisone, 50 mg, given orally once daily; Days 5 through 30: prednisone, 25 mg, given orally once daily; Days 31-44: prednisone, 22.5 mg, given orally once daily; Days 45-58: prednisone, 20 mg, given orally once daily

Intervention Type: DRUG

Other Intervention Names

LEA29Y, BMS-224818; The cyclosporine used in this study will be in the modified formulation with enhanced bioavailability.

Eligibility Criteria

Inclusion Criteria

• Recipients of first kidney transplant

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Univ. of Calif. - San Francisco

San Francisco, California, United States

Emory Univ. School of Medicine

Atlanta, Georgia, United States

Johns Hopkins University

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

Univ. of Nebraska Medical Center

Omaha, Nebraska, United States

Saint Barnabas Medical Center

Livingston, New Jersey, United States

Mount Sinai Medical Center

New York, New York, United States

Univ. of Pennsylvania

Philadelphia, Pennsylvania, United States

Medical Univ. of South Carolina

Charleston, South Carolina, United States

Baylor Univ. Medical Center

Dallas, Texas, United States

Univ. of Wisconsin

Madison, Wisconsin, United States

Countries

United States

Other Identifiers

IM103-100

Identifier Type: -

Identifier Source: org_study_id