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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Highly Sensitized Patients on Waiting List for Kidney Transplantation

Intervention / Treatment
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* Drug: Inebilizumab
* Drug: VIB4920
* Drug: Inebilzumab+VIB4920


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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. 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. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half lives of enrollment, whichever is longer. Subjects who have had more than one episode of severe infection requiring parenteral antimicrobial treatment within 12 months prior to screening. Subjects with a history of opportunistic infection within 12 months prior to screening (except for PO candidiasis, vaginal candidiasis, and cutaneous fungal infections). Subjects who have had more than one episode of herpes zoster within 12 months prior to screening. Subjects with uncontrolled diabetes mellitus (hemoglobin A1c ≥ 8.0% at screening). 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) 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. 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 carcinoma treated with apparent success with curative therapy. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inebilzumab Treatment<br>Infusion of Inebilizumab | Drug: Inebilizumab<br>* Infusion of Inebilizumab<br>|
| Experimental: VIB4920 Treatment<br>Infusion of VIB4920 | Drug: VIB4920<br>* Infusion of VIB4920<br>|
| Experimental: Inebilzumab+VIB4920 Treatment<br>Infusion of Inebilizumab and VIB4920 | Drug: Inebilzumab+VIB4920<br>* Infusion of Inebilizumab and VIB4920<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cPRA, HLA antibodies, kidney transplantation