Safety and Tolerability of Inebilizumab, VIB4920, or the Combination in Highly Sensitized Candidates Awaiting Kidney Transplantation From a Deceased Donor

NCT04174677 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: VIB0551.P2.S1
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

Viela Bio is conducting an open-label, randomized study of inebilizumab, VIB4920, or the combination as part of a multi-center study in highly sensitized patients on the deceased donor waiting list for kidney transplantation. Eligible subjects will be randomized to one of three treatment arms, administered the investigational products as an intervention and subsequently followed for safety.

Conditions

Highly Sensitized Patients on Waiting List for Kidney Transplantation

Keywords

cPRA, HLA antibodies, kidney transplantation

Outcome Measures

Primary Outcomes (1)

• Number of subjects with safety events (treatment-emergent adverse events, treatment-emergent serious adverse events, or treatment-emergent adverse events of special interest) during the course of the study

  Through study completion, an average of 1 year

Secondary Outcomes (4)

• Anti-drug antibodies (ADA) of inebilizumab and VIB4920

  Through study completion, an average of 1 year

• Maximum observed concentration of inebilizumab and VIB4920

  Treatment phase of study (Day 1 of treatment to Day 197)

• Area under the concentration-time curve of inebilizumab and VIB4920

  Treatment phase of study (Day 1 of treatment to Day 197)

• Total systemic clearance of inebilizumab and VIB4920

  Treatment phase of study (Day 1 of treatment to Day 197)

Other Outcomes (1)

• Proportion of subjects who achieve at least a 1-, 2-, 3-, or 4-titer reduction in anti-HLA antibody strength in at least 25% of antibodies present before treatment versus any post baseline visit

  Day 1 through study completion, an average of 1 year

Study Arms (3)

Inebilzumab Treatment

EXPERIMENTAL

Infusion of Inebilizumab

Drug: Inebilizumab

VIB4920 Treatment

EXPERIMENTAL

Infusion of VIB4920

Drug: VIB4920

Inebilzumab+VIB4920 Treatment

EXPERIMENTAL

Infusion of Inebilizumab and VIB4920

Drug: Inebilzumab+VIB4920

Interventions

Inebilizumab DRUG

Infusion of Inebilizumab

Inebilzumab Treatment

VIB4920 DRUG

Infusion of VIB4920

VIB4920 Treatment

Inebilzumab+VIB4920 DRUG

Infusion of Inebilizumab and VIB4920

Inebilzumab+VIB4920 Treatment

Eligibility Criteria

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

You may qualify if:

• Subjects with ESRD who are maintained on hemodialysis.
• Subjects awaiting first or second kidney transplantation from a deceased donor.
• Subjects with cPRA 98 100% at Screening Visit 1, calculated using antibodies with titer ≥ 1:16 and/or MFI value ≥ 1400, verified by the central laboratory.
• Subjects with stable anti-HLA antibody titers (a difference of \< 2 titers versus the average titer of antibodies compared to the screening sample) based on 2 legacy samples drawn within 6 to 12 months prior to Screening Visit 1, verified by the central laboratory.

You may not qualify if:

• Subjects awaiting kidney transplantation from a living donor.
• Subjects who have previously undergone desensitization with plasmapheresis/plasma exchange, IVIG, rituximab, imlifidase, tocilizumab or a proteasome inhibitor (eg, bortezomib, carfilzomib, ixazomib, others) within 12 months prior to randomization.
• Candidates for a second kidney allograft if the first allograft was lost within 12 months prior to screening.
• Subjects who have experienced a sensitizing event (eg, pregnancy, blood transfusion) within 6 months prior to screening.
• Recipients of a prior non-kidney organ transplant or stem cell transplant.
• Subjects treated with systemic immunosuppressive drug therapy for more than a total of 2 weeks within 12 months prior to ICF signature (treatment with corticosteroids \< 10 mg/day PO prednisone or equivalent for less than a total of 2 weeks during the 4 weeks prior to screening is allowed).
• Subjects who have undergone lympho-depleting therapy (eg, Thymoglobulin, alemtuzumab) within 12 months prior to randomization.
• Subjects with known immunodeficiency.
• Subjects with known platelet disorders, or history of arterial or venous thromboembolism unrelated to hemodialysis access procedures.
• Subjects with history of prothrombotic status (including but not limited to congenital or inherited deficiency of antithrombin III, protein C, protein S), or confirmed diagnosis of catastrophic antiphospholipid syndrome.
• Subjects requiring treatment with antithrombotic drugs (clopidogrel, prasugrel, warfarin, others). Low-dose aspirin treatment (up to 325 mg/day) is allowed.
• Major surgery within 12 weeks prior to screening.
• Receipt of live (attenuated) vaccine within the 4 weeks prior to screening.
• Previous treatment with anti-CD40L agents.
• Use of B-cell depleting therapy (eg, inebilizumab, rituximab, ocrelizumab, obinutuzumab), non-depleting B-cell directed therapy (eg, belimumab), an anti-CD40 agent, belatacept, or abatacept within 1 year prior to enrollment.

Sponsors & Collaborators

• Amgen: lead

Study Sites (2)

Reserach Site California

San Diego, California, 92123, United States

Location

Pennsylvania Reserach Site

Bethlehem, Pennsylvania, 18017, United States

Location

MeSH Terms

Interventions

inebilizumab

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: November 5, 2019
• First Posted: November 22, 2019
• Study Start: December 27, 2019
• Primary Completion: December 1, 2021
• Study Completion: April 1, 2022
• Last Updated: June 21, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

US (2)