A Study to Evaluate the Safety and Efficacy of Dual Costimulation Blockade With VIB4920 and Belatacept for Prophylaxis of Allograft Rejection in Adults Receiving a Kidney Transplant
Condition: Allografts; Rejection; Transplant, Kidney; Transplant Rejection; Kidney Transplantation
Intervention: Belatacept; VIB4920; Thymoglobulin; Methylprednisolone
Intervention description: Protocol versions 1 through 4: Belatacept 10 mg/kg by intravenous (IV) infusion on post-op Day 1, repeated on post-op Day 3 or 4 (timing is at investigator's discretion), and at the end of Weeks 2, 4, 8 and 12; then 5 mg/kg IV every 4 weeks from Week 16 to Week 48.; Protocol versions 1 and 2: VIB4920 1500 mg by IV infusion on post-op Days 1 and 14, and at the end of Weeks 4, 6, 8 and 10; then 1500 mg every 4 weeks from Week 12 to Week 48.
Protocol versions 3 and 4: VIB4920 1500 mg by IV infusion on post-op Days 1, repeated on post-op Day 3 or 4 (timing is at investigator's discretion), Week 2, and at the end of Weeks 4, 6, 8, and 10; then 1500 mg every 4 weeks from Week 12 to Week 48.; Protocol versions 1 and 2: Thymoglobulin 3.0 mg/kg by intravenous (IV) infusion prior to reperfusion of the allograft on the day of transplantation surgery (Day 0) (1 dose).
Protocol versions 3 and 4: Thymoglobulin 1.5 mg/kg by intravenous infusion prior to reperfusion of the allograft on the day of transplantation surgery (Day 0), prior to VIB4920+belatacept infusion on post-op Day 1, on post-op Day 2, and prior to VIB4920+belatacept infusion on post-op Day 3 or 4.; Protocol versions 1 and 2: Methylprednisolone by IV infusion (500, 250, 125 and 60 mg on Days 0, 1, 2 and 3, respectively) followed by oral administration of prednisone 30 mg per day on Days 4, 5, and 6.
Protocol versions 3 and 4: Methylprednisolone by IV infusion (500, 250, 125 and 60 mg on Days 0, 1, 2 and 3, respectively) followed by oral administration of prednisone 30 mg per day on Days 4, 5, 6 and 7. Participants may be tapered to at least 20 mg per day on Day 8, to at least 10 mg per day on Day 15, and to at least 5 mg per day on Day 22. Discontinuation of prednisone following the post-op Day 28 visit.
Intervention MeSH terms: Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Abatacept; Prednisolone hemisuccinate; Prednisolone phosphate; Thymoglobulin
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Renal allograft dysfunction; Cell-mediated rejection; Antibody mediated rejection; Immunosuppression; Acute rejection; VIB4920; MEDI4920; Belatacept; Thymoglobulin; Methylprednisolone; Corticosteroids

Summary:

      The purpose of this study is to evaluate the efficacy, safety and tolerability of dual
      costimulation blockade with VIB4920 in combination of belatacept in adult male or female
      recipients of a renal allograft from a deceased, living unrelated or human leukocyte antigen
      (HLA) non-identical living related donor.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Recipients of a first renal transplant from standard criteria deceased, living
             unrelated or HLA non-identical living related donor.

          -  Recipients who are at low immunologic risk:

               1. No donor specific antibodies (DSA), and

               2. Negative cross-match testing.

          -  Recipients with up to date vaccination as per local immunization schedules.

          -  Male and female participants who agree to follow protocol defined contraceptive
             methods.

        Exclusion Criteria:

          -  Participants receiving an allograft from an ABO-incompatible donor.

          -  Participants treated with systemic immunosuppressive drug therapy for more than a
             total of 2 weeks within 24 weeks prior to informed consent form signature.

          -  Participants who have undergone lymphodepleting therapy.

          -  Participants with medical history of confirmed venous thromboembolism, arterial
             thrombosis, coagulopathy or known platelet disorders.

          -  Participants with risk factors for venous thromboembolism or arterial thrombosis,
             prothrombotic status.

          -  Participants requiring treatment with antithrombotic drugs (clopidogrel, prasugrel,
             warfarin, others).

          -  Participants requiring long-term systemic anticoagulation after transplantation, which
             would interfere with obtaining biopsies.

          -  Participants with any contraindication to kidney biopsy.

          -  Cytomegalovirus (CMV)-seronegative recipients of a CMV-seropositive donor kidney, or
             unknown CMV serostatus.

          -  Epstein-Barr virus (EBV)-seronegative or with unknown EBV serostatus.

          -  Receipt of live (attenuated) vaccine within the 4 weeks before screening.

          -  Participants with high potential of graft loss due to recurrence of underlying kidney
             disease.

          -  Prior solid organ transplant or potential to require a concurrent organ or cell
             transplant.

          -  Previous treatment with belatacept and cluster of differentiation 40 (CD40) or
             anti-CD40L agents.

          -  Use of B cell depleting therapy, non-depleting B cell directed therapy e.g., belimumab
             or abatacept within 1 year prior to enrolment.

          -  At screening blood tests any of the following:

               1. Aspartate aminotransferase (AST) > 2.5 × upper limit of normal (ULN)

               2. Alanine aminotransferase (ALT) > 2.5 × ULN

               3. Alkaline phosphatase (ALP) > 2.5 × ULN

               4. Total bilirubin (TBL) > 2 × ULN

               5. Hemoglobin < 75 g/L

               6. Neutrophils < 1.5 × 10^9/L

               7. Platelets < 100 × 10^9/L

          -  Participants with severe systemic infections, current or within the 2 weeks prior to
             transplant surgery.

          -  Positive test for chronic hepatitis B infection at screening or within the last 12
             months.

          -  Positive test for hepatitis C virus antibody at screening or within the last 12
             months.

          -  Positive test for human immunodeficiency viruses antibody at screening or within the
             last 12 months.

          -  History of or active tuberculosis (TB), or a positive QuantiFERON®-TB Gold test at
             screening, unless previously treated for latent tuberculosis.

          -  History of cancer, except as follows:

               1. In situ carcinoma of the cervix treated with apparent success with curative
                  therapy > 12 months prior to screening; or

               2. Cutaneous basal cell or squamous cell carcinoma treated with apparent success
                  with curative therapy.

          -  Lactating or pregnant females.