Maintenance of renal transplant recipients. MedDRA version: 18.1 Level: PT Classification code 10023439 Term: Kidney transplant rejection System Organ Class: 10021428 - Immune system disorders
Conditions
Interventions
Product Name: Belatacept
Product Code: BMS-224818
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: BELATACEPT
CAS Number: 749867-37-6
Current Sponsor code: BMS-224818
Other
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Signed Written informed Consent, the subject or legal representative is willing to provide signed written informed consent. Adults with endstage renal disease (ESRD) scheduled to undergo transplantation of a non-HLA identical, living or standard criteria deceased (SCD) donor kidney; Subjects with serological evidence of prior exposure to EBV. Evidence of prior exposure is to be determined locally by positive testing for IgG antibodies directed against EBV firal capsid antigen (VCA) and Epstein-Barr nuclear antigen (EBNA). Historical results are acceptable. • Men and women, 18to 75 at Screening, inclusive; Women of childbearing potential (WOCBP) must use highly effective methods of birth control to avoid pregnancy throughout the study and for up to 8 weeks after the study in such a manner that the risk of pregnancy is minimized; Acceptable methods of highly effective birth control include: Condom with spermicide, Diaphragm and spermicide, Cervical cap and spermicide, Oral contraceptives, Intrauterine device (IUD); It should be noted that according to the US product information for mycophenolate mofetil (CellCept®), two reliable forms of contraception must be used simultaneously unless abstinence is the chosen method; WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of beta-human chorionic gonadotropin [ß-HCG]) within 24 hours prior to the start of study medication; Women must not be breastfeeding; Sexually active fertile men must use highly effective birth control if their partners are WOCBP. Men who are sexually active with WOCBP must follow instructions for birth control for the entire duration of the study and a minimum of 8 weeks post study drug has been completed; Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile; see Section 3.3.3 for the definition of WOCBP) and azoospermic men do not require contraception. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 144 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 96
Exclusion criteria
Exclusion criteria: Subjects who are seronegative for prior exposure to EBV or those whose EBV serologic status is unknown at randomization. Genetically-identical donor recipient pairs (ie, identical twins) Subjects with a recent (within 3 months prior to transplant) PRA more than or equal to 20%. Subjects with a past history of, or current need for desensitization therapy. Subjects with previous graft loss due to acute rejection Subjects with a positive T-cell or lymphocytotoxic cross match or any detectable donor specific antibodies prior to transplantation. Recipients of kidneys from donors 1.5 mg/dL;or -Recipients of kidneys donated after cardiac death. Subjects with prior or concurrent non-renal solid organ or cell (eg, pancreas or kidneypancreas, islet transplant or stem-cell) transplants and those deemed by the Investigator as being likely to require a non-renal transplant in the next 3 years.Subjects receiving paired (dual or en bloc kidney transplants). CMV negative subjects scheduled to receive a kidney from a CMV positive donor. Subjects with ESDR due to any of the following underlying conditions : primary focal segmental glomerulosclerosis, type I or II membranoproliferative glomerulonephritis,hemolytic uremic syndrome/Thrombotic Thrombocytopenic Purpura Hepatitis C virus (HCV): subjects or donors known to be positive for anti-HCV antibody or for HCV RNA detectable by polymerase chain reaction (PCR). Hepatitis B virus (HBV): subjects or donors known to be positive for hepatitis B surface antigen or for HBV DNA detectable PCR. Human immunodeficiency virus (HIV): subjects or donors known to be HIV positive. Subjects with current evidence or past history of active or inadequately treated latent TB infection: Subjects must have documentation of a chest x-ray (posterior-anterior and lateral views) that is negative for radiographic evidence of pulmonary TB within the last 6 months prior to transplant.A negative screening test for latent TB infection (LTBI) [intradermal PPD, or interferon-gamma release assay (IGRA) such as QuantiFERON TB Gold test or T-Spot-TB] that was performed at any time prior to the current transplant. Those subjects who do not have documented negative result specifically from an IGRA test performed within the last 3 months prior to randomization, must be screened for latent TB with an Interferon gamma release assay (IGRA) test performed during the Screening visit- TB. Results of IGRA are not required for randomization when the results from a historical negative screening test (PPD or IGRA) are available. If equipment for sample preparation prior to shipment to central lab is not available at the site, a local lab IGRA test is acceptable. If a historical negative screening test (PPD or IGRA) result for LTBI was available and the patient was randomized on that basis, but the Screening Visit IGRA is subsequently reported (post-transplant) to be positive, treatment for latent TB must be initiated upon receipt of the test result by the Investigator. Treatment may consist of isoniazid (INH, isonicotinic acid hydrazide), 300 mg p.o. once daily for 9 months or an alternative that is consistent with the local standard of care. History of biopsy-confirmed malignancy (other
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to assess the incidence of clinically-suspected and biopsy proven acute rejection (CSBPAR) at 6 months post-transplant in de novo renal allograft recipients treated with thymoglobulin induction, rapid corticosteroid withdrawal, and maintenance belatacept in combination with EVL, or maintenance TAC in combination with MMF.;Secondary Objective: The effects of each immunosuppressant regimen on the rates of acute rejection, subject and allograft survival and allograft function will be evaluated as follows : The frequency and severity of acute rejection at 6, 12 and 24 months post-transplant/Rates of subject and allograft survival at 6, 12 and 24 months post-transplant/Changes in renal function and severity of proteinuria at 3, 6, 12 and 24 months post-transplant/The frequency and type of donor-specific anti-HLA antibodies (DSA) detectable prior to, and at 12 and 24 months post-transplant/The safety and tolerability of each treatment regimen, as based upon the results of vital signs and safety laboratory assessments, and cumulative rates of adverse events reported at 6, 12, and 24 months post-transplant/ The frequency of cardiovascular and metabolic co-morbidities reported at 3, 6, 12, and 24 months post-transplant.;Primary end point(s): The incidence of CSBPAR at 6 months post-transplant, in the individual treatment groups: Belatacept + EVL; TAC + MMF. ;Timepoint(s) of evaluation of this end point: 6 months post-transplant. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Frequency and severity of acute rejection at 12 and 24 months post -transplant 2. Rates of subject and allograft survival at 6, 12 and 24 months post-transplant 3. Changes in renal function and severity of proteinuria at 3, 6, 12 and 24 months post-transplant 4. The frequency and type of donor specific anti-HLA antibodies (DSA) detectable prior to, and at 12 and 24 months post-transplant 5. Safety and tolerability of each treatment regimen 6. The frequency of cardiovascular and metabolic co-morbidities reported at 3, 6, 12, and 24 months post-transplant. ;Timepoint(s) of evaluation of this end point: 3, 6, 12 and 24 months post transplant. | — |
Countries
Argentina, Austria, Colombia, Germany, United States
Contacts
Public ContactEU Study Start-Up Unit
Bristol-Myers Squibb International Corporation
Outcome results
None listed