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

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Status and phase: Completed; Phase 2

Conditions: Kidney Transplantation; Allografts; Rejection; Transplant, Kidney; Transplant Rejection

Treatments: Drug: VIB4920; Drug: Thymoglobulin; Drug: Methylprednisolone; Drug: Belatacept

Study type: Interventional

Funder types: Industry

Identifiers

NCT04046549

VIB4920.P2.S1

Details and patient eligibility

About

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.

Enrollment: 25 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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25 participants in 1 patient group

Belatacept+VIB4920

Experimental group

Description:

Participants will be admitted to the transplant center for the administration of VIB4920 and belatacept (with Thymoglobulin and corticosteroids) and will be discharged on Day 3/4 at the discretion of the investigator. Participants will return to the study center to receive study drugs (VIB4920 and /or belatacept) weekly for 2 visits, then every 2 weeks for 5 visits, and then monthly for 9 visits for safety monitoring.

Treatment:

Drug: VIB4920

Drug: Belatacept

Drug: Methylprednisolone

Drug: Thymoglobulin