Belatacept in Liver Transplant Recipients
Condition: Immunosuppression in Solid Organ Transplant
Intervention: Tacrolimus; Basiliximab; Belatacept More Intensive (MI); Belatacept Less Intensive (LI); Mycophenolate Mofetil (MMF)
Intervention description: Capsules, Oral, dosed to achieve 12 hour trough level of 6-12 ng/mL, twice daily, 52 weeks (Short Term [ST]), in accordance with local practice and the package insert, 4 years (Long-Term Extension [LTE]); Intravenous (IV), 20 mg, Day1 and Day 5; Intravenous (IV),
10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24.
After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (Long-term extension [LTE]); Intravenous (IV),
10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12.
After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term [ST]), 5 mg/kg, every 4 weeks, 4 years (Long-Term Extension(LTE); Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (Short term [ST]), ≤ 1 g/day, 4 years (Long-term extension [LTE])
Intervention MeSH terms: Mycophenolic Acid; Abatacept; Tacrolimus; Basiliximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 260.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      The purpose of this clinical research study is to evaluate the effects of belatacept,
      relative to tacrolimus, on the incidence of rejection, graft loss and death in subjects
      receiving a liver transplant
    

Eligibility criteria:

        Inclusion Criteria:

          -  First time recipient of deceased donor liver transplant

          -  Age 18-70

          -  Hepatitis C virus (HCV) positive recipients

          -  For Long-term extension study-Subjects who have completed one year of study treatment
             (through Week 52)

        Target Disease Exclusions:

        Donor Exclusions a) Living donors b) ABO-incompatible donor recipient pairs c) Donor age <
        12 or > 65 years d) Non heart-beating donors e) Anticipated cold ischemia time > 14 hours
        f) Donor Disease i) Known Human immunodeficiency virus (HIV) infection ii) Hepatitis B
        virus (HBV) surface antigen-positive or polymerase chain reaction (PCR)-positive donor if
        HBV negative recipient iii) HCV antibody-positive or PCR positive donor if HCV negative
        recipient

        Recipient Exclusions g) Subjects with a history of hypercoagulable state h) Subjects with
        fulminant hepatic failure i) Subjects receiving a split or reduced liver j) Subjects who
        are Epstein-Barr virus (EBV) negative

        Medical History and Concurrent Diseases

          1. Subjects who have received 2 or more consecutive weeks of dialysis 1 month prior to
             enrollment OR anticipated to have prolonged dialysis post-transplantation

          2. Subjects with known intrinsic renal disease (e.g., a urine protein/ creatinine ratio >
             150 mg/g or the presence of an abnormal number of red blood cells (RBCs) or granular
             casts in the urine) AND calculated GFR < 40 ml/min/1.73 m^2 body surface area (BSA)
             (abbreviated Modification of Diet in Renal Disease [MDRD]). Subjects must have a
             calculated GFR assessment within 1 month prior to enrollment.

          3. Subjects with known HIV

          4. Subjects with any prior or concurrent solid organ (e.g., heart, kidney, pancreas) or
             cell (e.g., islet, bone marrow) transplant or subjects deemed likely to have a second
             solid organ or cell transplant (e.g., islet, bone marrow) within the next 3 years.

          5. Subjects with a history of cancer within the last 5 years

        Allergies and Adverse Drug Reactions

        a) Hypersensitivity to any medications that will be used in the protocol

        Prohibited Treatments and/or Therapies

          1. Subjects receiving immunosuppressive agent(s) (e.g., methotrexate, abatacept,
             infliximab, etanercept, chemotherapy, etc.) within the past 6 months for other
             indications such as an autoimmune disease

          2. Subjects who received maintenance corticosteroids at a dose of > 5 mg/day of
             prednisone (or equivalent) for at least 7 consecutive days within the prior year for
             an underlying chronic inflammatory or autoimmune disease

          3. Subjects who have used any investigational drug within 30 days prior to the Day 1
             visit

          4. Subjects previously treated with belatacept