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

NCT ID: NCT04046549

Last Updated: 2024-12-27

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

25 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-30

Study Completion Date

2023-03-22

Brief Summary

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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

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Study with completed results acquired from Horizon in 2024.

Conditions

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Allografts Rejection; Transplant, Kidney Transplant Rejection Kidney Transplantation

Keywords

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Renal allograft dysfunction Cell-mediated rejection Antibody mediated rejection Immunosuppression Acute rejection VIB4920 MEDI4920 Belatacept Thymoglobulin Methylprednisolone Corticosteroids

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Belatacept+VIB4920

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.

Group Type EXPERIMENTAL

Belatacept

Intervention Type 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.

VIB4920

Intervention Type 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.

Thymoglobulin

Intervention Type 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.

Methylprednisolone

Intervention Type 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.

Interventions

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Belatacept

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.

Intervention Type DRUG

VIB4920

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.

Intervention Type DRUG

Thymoglobulin

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.

Intervention Type DRUG

Methylprednisolone

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.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MD

Role: STUDY_DIRECTOR

Amgen

Locations

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Keck Medical Center of USC

Los Angeles, California, United States

Site Status

University of California, San Francisco

San Francisco, California, United States

Site Status

Duke University School of Medicine

Durham, North Carolina, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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VIB4920.P2.S1

Identifier Type: -

Identifier Source: org_study_id