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

A Phase 2 Open-label, Prospective, Randomized Study of Inebilizumab, VIB4920, or the Combination to Evaluate Safety and Tolerability in Highly Sensitized Candidates Awaiting Kidney Transplantation From a Deceased Donor

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.

Study Overview

• Status: Withdrawn
• Conditions: Highly Sensitized Patients on Waiting List for Kidney Transplantation
• Intervention / Treatment: Drug: Inebilizumab; Drug: VIB4920; Drug: Inebilzumab+VIB4920

Detailed Description

Study acquired from Horizon in 2024.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92123
      • Reserach Site California
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017
      • Pennsylvania Reserach Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects with ESRD who are maintained on hemodialysis.
2. Subjects awaiting first or second kidney transplantation from a deceased donor.
3. 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.
4. 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.

Exclusion Criteria:

1. Subjects awaiting kidney transplantation from a living donor.
2. 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.
3. Candidates for a second kidney allograft if the first allograft was lost within 12 months prior to screening.
4. Subjects who have experienced a sensitizing event (eg, pregnancy, blood transfusion) within 6 months prior to screening.
5. Recipients of a prior non-kidney organ transplant or stem cell transplant.
6. 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).
7. Subjects who have undergone lympho-depleting therapy (eg, Thymoglobulin, alemtuzumab) within 12 months prior to randomization.
8. Subjects with known immunodeficiency.
9. Subjects with known platelet disorders, or history of arterial or venous thromboembolism unrelated to hemodialysis access procedures.
10. 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.
11. Subjects requiring treatment with antithrombotic drugs (clopidogrel, prasugrel, warfarin, others). Low-dose aspirin treatment (up to 325 mg/day) is allowed.
12. Major surgery within 12 weeks prior to screening.
13. Receipt of live (attenuated) vaccine within the 4 weeks prior to screening.
14. Previous treatment with anti-CD40L agents.
15. 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.
16. Use of anti-interleukin (IL)-6 mAbs (eg, tocilizumab, clazakizumab), C1 esterase inhibitors, or complement inhibitors (eg, eculizumab) or imlifidase within 12 months prior to enrollment.
17. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half lives of enrollment, whichever is longer.
18. Subjects who have had more than one episode of severe infection requiring parenteral antimicrobial treatment within 12 months prior to screening.
19. Subjects with a history of opportunistic infection within 12 months prior to screening (except for PO candidiasis, vaginal candidiasis, and cutaneous fungal infections).
20. Subjects who have had more than one episode of herpes zoster within 12 months prior to screening.
21. Subjects with uncontrolled diabetes mellitus (hemoglobin A1c ≥ 8.0% at screening).

22. Subjects who have a positive test for, or have been treated for, hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.

    Regarding hepatitis B, positive test for chronic hepatitis B infection at screening, defined as either (1) positive hepatitis B surface antigen (HBsAg) or (2) a positive hepatitis B core antibody (anti-HBcAb)

23. History of or active tuberculosis (TB), or a positive QuantiFERON®-TB Gold test at screening, unless previously treated for latent TB. Subjects with an indeterminate QuantiFERON®-TB Gold test result can repeat the test, but if the repeat test is also indeterminate, they are excluded.

24. 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 carcinoma treated with apparent success with curative therapy.
25. Any severe cardiovascular, respiratory, endocrine, gastrointestinal, hematological, neurological, psychiatric, or systemic disorder that could impact the evaluation of safety and efficacy assessments or affect the subject's ability to participate in the study or the subject's safety.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Inebilzumab Treatment; Infusion of Inebilizumab	Drug: Inebilizumab; Infusion of Inebilizumab
Experimental: VIB4920 Treatment; Infusion of VIB4920	Drug: VIB4920; Infusion of VIB4920
Experimental: Inebilzumab+VIB4920 Treatment; Infusion of Inebilizumab and VIB4920	Drug: Inebilzumab+VIB4920; Infusion of Inebilizumab and VIB4920

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-drug antibodies (ADA) of inebilizumab and VIB4920	The ADA incidence rate will be summarized, where the incidence is the proportion of the subjects with ADA positive post-baseline only or boosted their pre existing ADA during the study period.	Through study completion, an average of 1 year
Maximum observed concentration of inebilizumab and VIB4920	Pharmacokinetic profile	Treatment phase of study (Day 1 of treatment to Day 197)
Area under the concentration-time curve of inebilizumab and VIB4920	Pharmacokinetic profile	Treatment phase of study (Day 1 of treatment to Day 197)
Total systemic clearance of inebilizumab and VIB4920	Pharmacokinetic profile	Treatment phase of study (Day 1 of treatment to Day 197)

Other Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Study record dates

Study Major Dates

• Study Start (Actual): December 27, 2019
• Primary Completion (Estimated): December 1, 2021
• Study Completion (Estimated): April 1, 2022

Study Registration Dates

• First Submitted: November 5, 2019
• First Submitted That Met QC Criteria: November 21, 2019
• First Posted (Actual): November 22, 2019

Study Record Updates

• Last Update Posted (Actual): June 21, 2024
• Last Update Submitted That Met QC Criteria: June 18, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: cPRA, HLA antibodies, kidney transplantation
• Additional Relevant MeSH Terms: Pathologic Processes; Death
• Other Study ID Numbers: VIB0551.P2.S1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No