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

Sponsor

Viela Bio (acquired by Horizon Therapeutics) (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04046549

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Allografts Rejection; Transplant, Kidney Transplant Rejection Kidney Transplantation	Drug: Belatacept Drug: VIB4920	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

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

Actual Study Start Date :

Oct 30, 2019

Actual Primary Completion Date :

Jun 18, 2022

Anticipated Study Completion Date :

Mar 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Belatacept+VIB4920 Participants will be admitted to the transplant center for the administration of VIB4920 and belatacept 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.	Drug: Belatacept Belatacept Dose 1 will be administered intravenously on post-op Day 1, repeated on post-op Day 3 or 4, and at the end of Weeks 2, 4, 8 and 12; then Dose 2 every four weeks from Week 16 to Week 48. Drug: VIB4920 VIB4920 Dose 1 will be administered intravenously on post-op Days 1, and 14, and at the end of Weeks 4, 6, 8 and 10; then will continue every four weeks from Week 12 to Week 48.

Arm

Intervention/Treatment

Experimental: Belatacept+VIB4920

Participants will be admitted to the transplant center for the administration of VIB4920 and belatacept 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.

Drug: Belatacept

Belatacept Dose 1 will be administered intravenously on post-op Day 1, repeated on post-op Day 3 or 4, and at the end of Weeks 2, 4, 8 and 12; then Dose 2 every four weeks from Week 16 to Week 48.

Drug: VIB4920

VIB4920 Dose 1 will be administered intravenously on post-op Days 1, and 14, and at the end of Weeks 4, 6, 8 and 10; then will continue every four weeks from Week 12 to Week 48.

Outcome Measures

Primary Outcome Measures

Number of Participants With Treated Biopsy-proven Acute Rejection (tBPAR) of Grade 1A or Higher, Graft Loss or Death at Week 24 [Week 24]

Secondary Outcome Measures

Incidence of Treated Biopsy-proven Acute Rejection (tBPAR), graft loss, death or loss to follow-up (LTFU) [Week 12, 24, 48]
Incidence of antibody-mediated rejection [Week 12, 24, 48]
Incidence of Treated Biopsy-proven Acute Rejection (tBPAR) [Week 12, 24, 48]
Incidence of Biopsy Proven Acute Rejection (BPAR) [Week 12, 24, 48]
Incidence of treated acute rejections [Week 12, 24, 48]
Proportion of Participants with De novo donor-specific antibodies (dnDSA) [Week 12, 24, 48]
Serum samples will be collected at the timepoints specified for de novo donor-specific antibodies (dnDSA) using solid phase (bead-based) assays.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts 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:

No donor specific antibodies (DSA), and
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:

Aspartate aminotransferase (AST) > 2.5 × upper limit of normal (ULN)
Alanine aminotransferase (ALT) > 2.5 × ULN
Alkaline phosphatase (ALP) > 2.5 × ULN
Total bilirubin (TBL) > 2 × ULN
Hemoglobin < 75 g/L
Neutrophils < 1.5 × 10^9/L
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:

In situ carcinoma of the cervix treated with apparent success with curative therapy > 12 months prior to screening; or
Cutaneous basal cell or squamous cell carcinoma treated with apparent success with curative therapy.

Lactating or pregnant females.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Keck Medical Center of USC	Los Angeles	California	United States	90033
2	University of California, San Francisco	San Francisco	California	United States	94143
3	Duke University School of Medicine	Durham	North Carolina	United States	27710
4	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390