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

NCT00035555 | Completed Phase 2 Results

• 1 other identifier: IM103-100
• Study Type: interventional
• Target: 230
• Locations: 1 country
• Sites: 12

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

Keywords

kidney; transplant; rejection

Outcome Measures

Primary Outcomes (1)

• Number of Participants With an Episode of Clinically-suspected and Biopsy-proven Acute Rejection (CSPAR)

  No participant was to receive treatment for acute rejection without a biopsy to confirm the diagnosis. CSPAR=Clinically-suspected rejection, defined as an increase in serum creatinine ≥0.5 mg/dL compared with the baseline value in the absence of other factors known to adversely affect renal function, and biopsy-proven rejection, which includes all cases in which a biopsy was read by the central pathologist as demonstrating acute rejection regardless of the reason why the biopsy was performed.

  By Month 6 posttransplant (From Day 1 to Month 6)

Secondary Outcomes (9)

• Percentage of Participants With Biopsy-proven Acute Rejection (BPAR) Through Months 6 and 12

  Through Months 6 and 12 posttransplant (From Day 1 to Months 6 and 12)

• Percentage of Participants With Biopsy-proven Acute Rejection (BPAR) or Who Received Treatment for Acute Rejection

  By Months 3, 6, and 12 posttransplant (Day 1 to Months 3, 6, and 12)

• Percentage of Participants With Acute Rejection or Presumed Acute Rejection (PAR)

  By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)

• Percentage of Participants Who Had Chronic Allograft Nephropathy

  By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)

• Mean Iohexol Clearance

  By Months 1, 6, and 12 posttransplant (Day 1 to Months 1, 6, and 12)

Other Outcomes (2)

• Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, and Discontinuations Due to AEs

  Day 1 (posttransplant) continuously to 56 days following last dose of study medication

• Number of Participants Meeting Marked Abnormality Criteria for Select Hemolytic, Blood Chemistry, and Urinalysis Laboratory Test Results

  Days 8 and Months 1, 3, 6, 9, and 12 posttransplant (from Day 1)

Study Arms (3)

Belatacept: More intensive (MI) regimen

EXPERIMENTAL

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.

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

Belatacept: Less intensive (LI) regimen

EXPERIMENTAL

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.

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

Cyclosporine regimen

EXPERIMENTAL

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.

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

Interventions

Belatacept DRUG

Solution, intravenous

Also known as: LEA29Y, BMS-224818

Belatacept: Less intensive (LI) regimen; Belatacept: More intensive (MI) regimen

Cyclosporine DRUG

Oral, capsule

Also known as: The cyclosporine used in this study will be in the modified formulation with enhanced bioavailability.

Cyclosporine regimen

Mycophenolate mofetil (MMF) DRUG

Oral, capsule

Belatacept: Less intensive (LI) regimen; Belatacept: More intensive (MI) regimen; Cyclosporine regimen

Corticosteroids 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; Belatacept: More intensive (MI) regimen; Cyclosporine regimen

Eligibility Criteria

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

You may qualify if:

• Recipients of first kidney transplant

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (12)

Univ. of Calif. - San Francisco

San Francisco, California, 94143-0001, United States

Location

Emory Univ. School of Medicine

Atlanta, Georgia, 30322, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21205, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Univ. of Nebraska Medical Center

Omaha, Nebraska, 68198-1002, United States

Location

Saint Barnabas Medical Center

Livingston, New Jersey, 07039, United States

Location

Mount Sinai Medical Center

New York, New York, 10029-6574, United States

Location

Univ. of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Medical Univ. of South Carolina

Charleston, South Carolina, 29425, United States

Location

Baylor Univ. Medical Center

Dallas, Texas, 75246, United States

Location

Univ. of Wisconsin

Madison, Wisconsin, 53792-7375, United States

Location

MeSH Terms

Conditions

Rejection, Psychology

Interventions

Abatacept; Cyclosporine; Mycophenolic Acid; Adrenal Cortex Hormones

Condition Hierarchy (Ancestors)

Social Behavior; Behavior

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2002
• First Posted: May 6, 2002
• Study Start: March 1, 2001
• Primary Completion: January 1, 2004
• Study Completion: July 1, 2012
• Last Updated: January 13, 2014
• Results First Posted: January 13, 2014

Record last verified: 2013-11

Locations

US (12)