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

NCT04046549 | Completed Phase 2 Results FDA Drug

• 1 other identifier: VIB4920.P2.S1
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 4

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.

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

Outcome Measures

Primary Outcomes (1)

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

  Histological grading of acute allograft rejection from biopsy specimens was based on Banff criteria 2017. Grade IA: Moderate tubulitis and at least moderate total cortical inflammation and at least moderate scarred cortical inflammation and other known causes ruled out. Grade IB: Severe tubulitis and at least moderate total cortical inflammation and at least moderate scarred cortical inflammation and other known causes ruled out. Grade II. Arterial intimal fibrosis with mononuclear cell inflammation, formation of neointima.

  Week 24

Secondary Outcomes (7)

• Percentage of Participants With Treated Biopsy-proven Acute Rejection (tBPAR) of Grade 1A or Higher, Graft Loss or Death at Weeks 12 and 48

  Weeks 12 and 48

• Percentage of Participants With Treated Biopsy-proven Acute Rejection (tBPAR), Graft Loss, Death or Loss to Follow-up (LTFU)

  Week 12, 24, 48

• Percentage of Participants With Antibody-Mediated Rejection

  Week 12, 24, 48

• Percentage of Participants With Treated Biopsy-proven Acute Rejection (tBPAR)

  Week 12, 24, 48

• Percentage of Participants With Biopsy Proven Acute Rejection (BPAR)

  Week 12, 24, 48

Study Arms (1)

Belatacept+VIB4920

EXPERIMENTAL

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.

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

Interventions

Belatacept DRUG

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.

Belatacept+VIB4920

VIB4920 DRUG

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.

Belatacept+VIB4920

Thymoglobulin DRUG

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.

Belatacept+VIB4920

Methylprednisolone DRUG

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.

Belatacept+VIB4920

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead

Study Sites (4)

Keck Medical Center of USC

Los Angeles, California, 90033, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Duke University School of Medicine

Durham, North Carolina, 27710, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Rejection, Psychology

Interventions

Abatacept; thymoglobulin; Methylprednisolone

Condition Hierarchy (Ancestors)

Social Behavior; Behavior

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Todd Wilson, DO
• Organization: Horizon Therapeutics USA, Inc.

clinicaltrials@horizontherapeutics.com

866-479-6742

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2019
• First Posted: August 6, 2019
• Study Start: October 30, 2019
• Primary Completion: July 18, 2022
• Study Completion: March 22, 2023
• Last Updated: December 27, 2024
• Results First Posted: October 10, 2023

Record last verified: 2024-12

Locations

US (4)