A Study of Inebilizumab Efficacy and Safety in IgG4- Related Disease

Study Overview
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Brief Summary
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This study aims to evaluate the efficacy and safety of inebilizumab for the prevention of flare of Immunoglobulin G4-related disease (IgG4-RD).

Detailed Description
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After a screening period of up to 28 days, subjects with IgG4-RD at high risk of flare due to multi-organ disease and recent active disease will be randomized in a 1:1 ratio to receive intravenous (IV) inebilizumab or placebo after premedication during the 52-week randomized control period (RCP). All subjects will receive an initial tapering dose of glucocorticoids (GCs) to complete treatment of their active disease. Flares occurring during study will be treated. The primary endpoint is time to a first adjudication committee-determined, investigator-treated disease flare during the RCP. The primary analysis will be conducted when the last subject completes the RCP visit or discontinues the RCP. This study includes an optional 3-year open-label treatment period. The study also includes a Safety Follow-up Period (SFUP) after IP discontinuation of up to 730 days. The expected duration of each subject's participation in this study is up to 400 days (screening and RCP), plus up to 1095 days for eligible subjects who enroll in the optional open label period (OLP), and up to 730 days for the SFUP after IP discontinuation, for a total maximum duration of up to 2273 days (screening, RCP, interval between RCP and OLP, OLP, and FSUP).

Official Title
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A Phase 3, Randomized, Double-blind, Multicenter, Placebo Controlled Study of Inebilizumab Efficacy and Safety in IgG4-Related Disease

Conditions
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IgG4 Related Disease

Intervention / Treatment
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* Drug: Inebilizumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or female adults, ≥ 18 years of age at time of informed consent. Clinical diagnosis of IgG4-RD. Fulfillment of the 2019 ACR/EULAR classification criteria. Experiencing (or recently experienced) an IgG4-RD flare that requires initiation or continuation of glucocorticoid (GC) treatment at the time of informed consent. IgG4-RD affecting at least 2 organs/sites at any time in the course of IgG4-RD Non-sterilized male subjects who are sexually active with a female partner of childbearing potential must use a condom with spermicide from Day 1 through to the end of the study and must agree to continue using such precautions for at least 6 months after the final dose of IP. Females of childbearing potential who are sexually active with a non-sterilized male partner must use a highly effective method of contraception Key Exclusion Criteria: History of solid organ or cell-based transplantation or known immunodeficiency disorder. Active malignancy or history of malignancy that was active within the last 10 years (some specific situations for cervical, skin or prostate cancer are acceptable). Receipt of any biologic B cell-depleting therapy or non-depleting B-cell-directed therapy in the 6 months prior to screening. Receipt of non-biologic DMARD or immunosuppressive agent other than GCs within 4 weeks prior to screening. Active tuberculosis or high risk for tuberculosis; hepatitis C infection in absence of curative treatment; evidence of hepatitis B infection. Receipt of live vaccine or live therapeutic infectious agent within 2 weeks prior to screening. Estimated glomerular filtration rate < 30 mL/min/1.73 m^2.

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VIB0551<br>Inebilizumab administered as an IV infusion. | Drug: Inebilizumab<br>* Inebilizumab is a monoclonal antibody that depletes B cells.<br>|
| Placebo Comparator: Placebo<br>Placebo administered as an IV infusion. | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to disease flare, defined as the time in days from Day 1 (dosing) to the date of the first treated and Adjudication Committee-determined IgG4 RD flare within the 52-week RCP. |  | Day 1 to Day 365 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Treatment Emergent Adverse Events (TEAEs) |  | Day 1 to Day 2273 | 
| Number of participants with Treatment Emergent Serious Adverse Events (TESAEs) |  | Day 1 to Day 2273 | 
| Number of participants with Treatment Emergent Adverse Events of Special Interest (TE AESIs) |  | Day 1 to Day 2273 | 
| Number of Participants with positive Anti Drug Antibodies (ADAs) directed against inebilizumab |  | Day 1 to Day 365 | 
| Annualized flare rate for treated flares |  | Day 1 to Day 365 | 
| Annualized flare rate for Adjudication Committee (AC) determined flares |  | Day 1 to Day 365 | 
| Annualized flare rate for AC-determined treated flares |  | Day 1 to Day 365 | 
| Annualized flare rate for AC-determined untreated flares |  | Day 1 to Day 365 | 
| Proportion of participants achieving flare-free complete remission |  | Day 1 to Day 365 | 
| Time to initiation of first treatment for new or worsening disease activity |  | Day 1 to Day 365 | 
| GC use for the purpose of IgG4-RD disease control |  | Day 1 to Day 365 |