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

Kidney Transplantation Clinical Trial

Official title:

Phase II/III, Open-Label, Randomized, Controlled, Multiple-Dose Study of Efficacy and Safety of BMS-224818 (Belatacept) as Part of a Quadruple Drug Regimen in First Renal Transplant Recipients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00035555
• Other study ID #: IM103-100
• Status: Completed
• Phase: Phase 2
• First received: May 3, 2002
• Last updated: November 27, 2013
• Start date: March 2001
• Est. completion date: July 2012

Study information

• Verified date: November 2013
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 230
• Est. completion date: July 2012
• Est. primary completion date: January 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Graft Rejection
• Kidney Transplantation
• Renal Transplantation

Intervention

Drug:
• Belatacept
Solution, intravenous
• Cyclosporine
Oral, capsule
• Mycophenolate mofetil (MMF)
Oral, capsule
• 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

Locations

Country	Name	City	State
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	Medical Univ. of South Carolina	Charleston	South Carolina
United States	Baylor Univ. Medical Center	Dallas	Texas
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	Univ. of Wisconsin	Madison	Wisconsin
United States	Mount Sinai Medical Center	New York	New York
United States	Univ. of Nebraska Medical Center	Omaha	Nebraska
United States	Univ. of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	Univ. of Calif. - San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug.	Day 1 (posttransplant) continuously to 56 days following last dose of study medication	Yes
Other	Number of Participants Meeting Marked Abnormality Criteria for Select Hemolytic, Blood Chemistry, and Urinalysis Laboratory Test Results	Normal laboratory values: Hemoglobin (g/dL): Males (18-64 years) 13.8-17, (65 years and older) 11.8-16.8; Females (18-64 years) 12.0-15.6, F (65 years and older) 11.1-15.5. Platelets (per mm^3) 130,000-400,000. Leukocytes (18 years and older) 3.8-10.8 1000/uL. ALT (u/L)(13 years and older) 0-48.	Days 8 and Months 1, 3, 6, 9, and 12 posttransplant (from Day 1)	Yes
Primary	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)	Yes
Secondary	Percentage of Participants With Biopsy-proven Acute Rejection (BPAR) Through Months 6 and 12	BPAR includes all cases in which a biopsy read by the central pathologist demonstrates acute rejection, regardless of the reason that the biopsy was performed.	Through Months 6 and 12 posttransplant (From Day 1 to Months 6 and 12)	Yes
Secondary	Percentage of Participants With Biopsy-proven Acute Rejection (BPAR) or Who Received Treatment for Acute Rejection	BPAR includes all cases in which a biopsy read by the central pathologist demonstrates acute rejection, regardless of the reason that the biopsy was performed. A participant was reported as having had an episode of treated acute rejection if he or she received antirejection therapy during an episode of rejection (clinically-suspected or biopsy-proven rejection).	By Months 3, 6, and 12 posttransplant (Day 1 to Months 3, 6, and 12)	Yes
Secondary	Percentage of Participants With Acute Rejection or Presumed Acute Rejection (PAR)	Throughout this study, acute rejection=clinically-suspected and biopsy-proven acute rejection (BPAR). Clinically-suspected rejection is 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. BPAR 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. PAR is defined as an elevation in SCr =0.5 mg/dL compared with the baseline value in the absence of other factors known to adversely affect renal function that led the investigator to suspect that the participant had experienced acute rejection, and in whom either the biopsy did not confirm acute rejection and the participant received treatment for acute rejection or the participant received treatment for acute rejection without a biopsy to confirm the diagnosis.	By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)	Yes
Secondary	Percentage of Participants Who Had Chronic Allograft Nephropathy	Based on postbaseline biopsies	By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)	Yes
Secondary	Mean Iohexol Clearance	Iohexol, a true glomerular filtration marker, is used to measure glomerular filtration rate.	By Months 1, 6, and 12 posttransplant (Day 1 to Months 1, 6, and 12)	Yes
Secondary	Percentage of Participants Who Used Antihypertensive Medication	Hypertension is defined as diastolic blood pressure =90 mm Hg and/or systolic blood pressure =140 mm Hg	By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)	Yes
Secondary	Number of Participants With Hypertension	Hypertension is defined as diastolic blood pressure =90 mm Hg and/or systolic blood pressure =140 mm Hg or, the use of any antihypertensive medication.	By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)	Yes
Secondary	Mean LDL Cholesterol, HDL Cholesterol, Total Cholesterol, Triglyceride, and Non-HDL Levels	LDL=low-density lipoprotein; HDL=high-density lipoprotein. Total cholesterol=LDL + HDL + very low-density (VLDL) cholesterol. VLDL=triglycerides divided by 5. Non-HDL cholesterol=Total cholesterol minus HDL cholesterol.	By Months 1, 6, and 12 posttransplant (Day 1 to Months 1, 6, and 12)	Yes
Secondary	Number of Participants With Posttransplant Diabetes Mellitus	Posttransplant diabetes mellitus is defined as the need for treatment of hyperglycemia with either an oral agent or insulin for a total of >4 weeks or hemoglobin A1c (HbA1c) >7% in a participant not known to be diabetic prior to transplantation	By Months 1, 3, 6, 9, and 12 posttransplant (Day 1 to Months 1, 3, 6, 9, and 12 )	No

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link www.fda.gov/MEDWATCH/safety.htm