Clinical trial NCT04046549: 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
Official title: A Phase 2a Single-arm, Prospective, Open-label Pilot 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Allografts
Rejection; Transplant, Kidney
Transplant Rejection
Kidney Transplantation
Keywords: Renal allograft dysfunction
Cell-mediated rejection
Antibody mediated rejection
Immunosuppression
Acute rejection
VIB4920
MEDI4920
Belatacept
Thymoglobulin
Methylprednisolone
Corticosteroids
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2019-08-06
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief 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.

Detailed description: 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.

Primary outcomes:
measure: Percentage of Participants With Treated Biopsy-proven Acute Rejection (tBPAR) of Grade 1A or Higher, Graft Loss or Death at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of Participants With Treated Biopsy-proven Acute Rejection (tBPAR) of Grade 1A or Higher, Graft Loss or Death at Weeks 12 and 48
timeFrame: Weeks 12 and 48
measure: Percentage of Participants With Treated Biopsy-proven Acute Rejection (tBPAR), Graft Loss, Death or Loss to Follow-up (LTFU)
timeFrame: Week 12, 24, 48
measure: Percentage of Participants With Antibody-Mediated Rejection
timeFrame: Week 12, 24, 48
measure: Percentage of Participants With Treated Biopsy-proven Acute Rejection (tBPAR)
timeFrame: Week 12, 24, 48
measure: Percentage of Participants With Biopsy Proven Acute Rejection (BPAR)
timeFrame: Week 12, 24, 48
measure: Percentage of Participants With Treated Acute Rejections
timeFrame: Week 12, 24, 48
measure: Percentage of Participants With De Novo Donor-specific Antibodies (dnDSA)
timeFrame: Week 12, 24, 48
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Keck Medical Center of USC
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Durham
country: United States
facility: Duke University School of Medicine
state: North Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: