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

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

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.

study with completed results acquired from horizon in 2024.

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.

Keywords: renal allograft dysfunction cell-mediated rejection antibody mediated rejection immunosuppression acute rejection vib4920 medi4920 belatacept thymoglobulin methylprednisolone corticosteroids