Mechanisms of Belatacept Effect on Alloimmunity and Antiviral Response After Kidney Transplantation (BMS IM 103-309)
Condition: Renal Transplant Rejection
Intervention: Belatacept
Intervention description: Subjects will receive intravenous belatacept at 5mg/kg every other week starting from day 1 and continuing with weeks 2, 4, 6, and 8, and then monthly at months 3, 4, 5, and 6. At month 6 patients may elect to continue for an additional six-month period of belatacept administration.
Intervention MeSH terms: Abatacept
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This research evaluates the effectiveness of a new drug called belatacept (Nulojix) for the
      prevention of acute rejection and preservation of kidney function in transplant patients.
      Belatacept was approved in 2011 by the United States Food and Drug Administration (FDA) and
      is being marketed as Nulojix. The pharmaceutical company sponsoring this study is
      Bristol-Myers Squibb.

      Belatacept is a prescription medicine used in adults to prevent transplant rejection in
      people who have received a kidney transplant. Transplant rejection happens when the body's
      immune system senses that the new transplanted kidney is different or foreign, and attacks
      it. Belatacept is used with corticosteroids and certain other medicines to help prevent
      rejection of your new kidney.

      The purpose of the research is to understand whether the new drug, belatacept, is better than
      other anti-rejection drugs, such as cyclosporine and tacrolimus that are typically used in
      the treatment against kidney rejection in transplant patients.
    

Eligibility criteria:

        Inclusion Criteria:

          1. The subject is willing to provide signed written informed consent Target Population

          2. The subject is a first-time recipient of a living or deceased donor kidney transplant

          3. Evidence of calcineurin inhibitor side effects during the first 3 months after
             transplant as defined as

        1. Neurologic toxicity, defined as tremor, altered mental status, or seizure 2. Renal
        toxicity, defined as glomerular filtration rate (GFR) <60 3. Metabolic toxicity, defined as
        a new requirement for medication to control hyperglycemia 4. Hematologic toxicity, defined
        as development of thrombotic microangiopathy Age and Gender 4) Men and women, ages 18 and
        older, inclusive 5) Women of childbearing potential (WOCBP) must be using an adequate
        method of contraception 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. Refer to the protocol
        for details regarding description and handling of WOCBP subjects.

        WOCBP must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent
        units of human chorionic gonadotropin (HCG)) within 72 hours prior to the start of study
        medication then every 3 months during the period of study participation.

        6) Men must use an adequate method of contraception throughout the study, and for up to 8
        weeks after the last infusion, so that the risk of pregnancy to their partners is
        minimized.

        7) Mycophenolate mofetil (MMF) must be dosed at 500 mg by mouth twice daily or greater at
        the time of study entry 8) Prednisone must be dosed at >=10 mg by mouth daily for patients
        less than 6 weeks post-transplantation, and at >=5mg by mouth daily for patients greater
        than 6 weeks post-transplantation at the time of study entry.

        Exclusion Criteria:

          1. WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for
             the entire study period and for up to 8 weeks after the last infusion.

          2. Women who are pregnant or breastfeeding

          3. Women with a positive pregnancy test on enrollment or prior to study drug
             administration

          4. Males unwilling or unable to use an adequate method of contraception for the entire
             study period and for up to 8 weeks after the last infusion of study medication
             Immunologic status

          5. Subjects with panel reactive antibody (PRA) ≥ 30% at time of transplant

          6. Subjects with zero human leukocyte antigen (HLA) mismatched donors (either from
             related or unrelated donor)

          7. Subjects with any prior solid organ transplant (including kidney)

          8. Subjects receiving a concurrent solid organ (heart, liver, pancreas) or cell (islet,
             bone marrow, stem cell) transplant

          9. Subjects with a history of biopsy-proven acute rejection post-transplant (humoral or
             cellular) in the first three months post transplantation Infection related risks

         10. Subjects who are hepatitis C antibody-positive or polymerase chain reaction
             (PCR)-positive for hepatitis C

         11. Subjects who are hepatitis B surface antigen-positive or PCR-positive for hepatitis B

         12. Subjects with known human immunodeficiency virus (HIV) infection

         13. Subjects with active tuberculosis (TB) requiring treatment within the previous 3 years
             or any subject who previously required triple (or more) combination therapy for TB.

         14. Subjects who are Epstein-Barr virus (EBV) antibody negative and have received grafts
             from EBV antibody positive donors.

             Prohibited Therapies and/or Medications

         15. Subjects who have used any investigational drug within 30 days prior to the Day 1
             visit

         16. Subjects previously treated with belatacept

         17. Use of mammilian target of rapamycin (mTOR) inhibitors at any time after
             transplantation