A Phase II Study of Belatacept (BMS-224818) With a Steroid-free Regimen in Subjects Undergoing Kidney Transplantation

• AR [ Time Frame: by 6/12 months ] [ Designated as safety issue: Yes ]
• Death/graft loss [ Time Frame: by 12 months ] [ Designated as safety issue: Yes ]
• AR/death/graft loss [ Time Frame: by 6 and 12 months ] [ Designated as safety issue: Yes ]
• Metabolic/cardiovascular (CV) comorbidity [ Time Frame: by 12 months ] [ Designated as safety issue: Yes ]
• Renal function [ Time Frame: by 12 months ] [ Designated as safety issue: Yes ]
• Corticosteroid-free subjects [ Time Frame: at 12 months ] [ Designated as safety issue: Yes ]
• Treatment discontinuation [ Time Frame: by 12 months ] [ Designated as safety issue: Yes ]
• Safety and tolerability of different corticosteroid-free belatacept-based immunosuppressive regiments in subjects who have received a kidney transplant and completed 12 months of study treatment [ Time Frame: until month 36 ] [ Designated as safety issue: Yes ]

• AR by 6/12 months
• Death/graft loss by 12 months
• AR/death/graft loss by 6 and 12 months
• Metabolic/CV comorbidity by 12 months
• Renal function by 12 months
• Corticosteroid-free subjects at 12 months
• Treatment discontinuation by 12 months
• Safety

The purpose of this clinical research study is to learn if belatacept (BMS-224818) is expected to show acceptable rates of acute rejection (AR) in steroid-free belatacept-based immunosuppressive regiments compared to a similar steroid-free tacrolimus regimen. The long-term safety and tolerability of belatacept based regimens following long-term administration in subjects who have received a kidney transplant

• Drug: Thymoglobulin
  Induction therapy, IV infusion, All subjects will receive thymoglobulin 1.5-mg/kg i.v. infusion on Days 1 (day of transplant), 2, 3, and 4 (up to a maximum total dose of 6 mg/kg) i.v. infusion over at least 4 hours
• Drug: Belatacept
  Belatacept arms will receive i.v. belatacept (10 mg/kg) on Days 1 and 5, and then every other week through Month 3 (Weeks 2, 4, 6, 8, 10, and 12), and then every 4 weeks through Month 6 (Weeks 16, 20, and 24). After 6 months, subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial
  Other Name: BMS-224818
• Drug: Sirolimus
  Sirolimus will be initiated at 5 mg/day on Day 1 (day of transplant) and continued through Day 2. The dosing will be adjusted subsequently to keep pre-dose (C0) levels at 7 - 12 ng/mL for the first 6 months, followed by 5 - 10 ng/mL thereafter
• Drug: Tacrolimus
  The recommended total initial dose of tacrolimus is 0.1 mg/kg/day in two divided doses orally up to and including week 52. Post week 52 subjects assigned to the tacrolimus arm will receive tacrolimus orally in accordance with local practice and the package insert until completion of the trial
• Drug: Mycophenolate Mofetil (MMF)
  Administered orally in a capsule or solution formulation in 2 divided doses on a consistent schedule in relation to time of day and meals. The dose should be 1 g bid; however 1.5 g bid may be administered at the investigator's discretion until completion of the trial

• Experimental: A
  Interventions:

  • Drug: Thymoglobulin
  • Drug: Belatacept
  • Drug: Mycophenolate Mofetil (MMF)
• Experimental: B
  Interventions:

  • Drug: Thymoglobulin
  • Drug: Belatacept
  • Drug: Sirolimus
• C
  (IMPs as comparator regimen)
  Interventions:

  • Drug: Thymoglobulin
  • Drug: Tacrolimus
  • Drug: Mycophenolate Mofetil (MMF)

Inclusion Criteria:

• Living or deceased donor renal allograft
• Men and women, 18 to 70 years old
• Subjects who have received a de novo kidney transplant, who have completed the initial study treatment through Month 12, and are willing to sign informed consent will be eligible to continue into the long term extension phase

Exclusion Criteria:

• Pregnant or breastfeeding women
• Epstein Barr Virus (EBV) negative serology
• First time renal transplant with panel reactive antibody (PRA) ≥ 50% or retransplantation with PRA > 30%
• Graft loss due to AR
• Positive T-cell or B-cell crossmatch
• Recipients/donors with HIV or hepatitis B/C
• Active tuberculosis (TB)
• Immunosuppressive therapy within 1 year of enrollment
• UNOS ECD organs will be excluded
• Body mass index (BMI) > 35 kg/m²
• Subjects who have developed any malignancy (other than non-melanoma skin cancer) or other medical condition that, in the investigator's opinion, should not be treated with an experimental immunosuppressive drug like belatacept