A Phase 3 Study of Obexelimab in Patients With IgG4-Related Disease

Study Overview
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Brief Summary
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This study aims to examine the efficacy and safety of obexelimab for the prevention of flare of IgG4-related disease (IgG4-RD)

Detailed Description
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This study consists of a 1-year randomized control period (RCP), followed by an additional 1-year open label extension (OLE) period. To enter the Screening Period (Day -28 to Day -1), patients must have active IgG4-RD signs/symptoms (i.e., flare) that require steroid therapy. On Day 1, patients will be randomized in a ratio of 1:1 to receive either obexelimab or placebo administered as subcutaneous (SC) injections. All patients will begin a steroid taper on Day 1 to discontinuation by Week 8. Patients will be monitored for flares during scheduled in clinic visits and any unscheduled visits. The primary endpoint is time to first IgG4-RD flare that requires initiation of rescue therapy in the opinion of the investigator and the Adjudication Committee (AC). Following the 52-week RCP, patients will have the opportunity to continue in an OLE period where all patients will receive obexelimab. Patients who do not wish to enroll into the OLE period will return for an in-clinic safety follow-up visit 8 weeks after the Week 52 visit (i.e., Week 60). Including screening and follow-up, the maximum duration of participation in this study for an individual patient is 116 weeks (i.e., 28-day screening, 52-week RCP, 52-week OLE, and an 8-week follow-up).

Official Title
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A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Obexelimab in Patients With IgG4-Related Disease (INDIGO)

Conditions
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IgG4 Related Disease

Intervention / Treatment
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* Drug: Obexelimab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females, ≥ 18 years of age Clinical diagnosis of IgG4-RD Patients must meet the 2019 ACR/EULAR Classification Criteria for IgG4-RD Patients must have active IgG4-RD signs/symptoms (i.e., flare) that require the initiation of GC therapy or the increase in background long-term GC therapy Other inclusion criteria apply Exclusion Criteria: Has disease in only 1 organ system whose primary manifestation is fibrosis Has received prednisone equivalent given orally at a dose greater than 60 mg/day within the 4 weeks prior to screening or during screening Has received a non-biologic, disease-modifying anti-rheumatological drug or immunosuppressive agent other than GCs within the 4 weeks prior to screening Has received an investigational treatment or direct medical intervention on another clinical study within 12 weeks or < 5 half-lives of the investigational treatment, whichever is shorter, prior to screening Has received live vaccine or live therapeutic infectious agent within the 2 weeks prior to screening Active tuberculosis or high risk for tuberculosis; hepatitis C infection in absence of curative treatment; evidence of hepatitis B infection Use of B cell depleting or targeting agents within 6 months of randomization Other exclusion criteria apply

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: ZB012<br>Obexelimab administered as an SC injection. | Drug: Obexelimab<br>* Obexelimab is a monoclonal antibody that simultaneously binds CD19 and FcγRIIb, resulting in down regulation of B cell activity.<br>|
| Placebo Comparator: Placebo<br>Placebo administered as an SC injection. | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary outcome measure | Time to first IgG4-RD flare, defined as the reappearance of previous signs/symptoms or appearance of new signs/symptoms of IgG4-RD that requires initiation of rescue therapy in the opinion of the investigator and the Adjudication Committee (AC), from randomization to Week 52. | Randomization to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IgG4, IgG4-RD