Open Label Two-Arm Study to Evaluate Rilzabrutinib in IgG4-Related Disease Patients

Study Overview
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Brief Summary
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This is a Phase 2a, multi-center, open-label, two-arm study of approximately 25 patients with active IgG4-related disease (IgG4-RD). The two arms include (1) Experimental: rilzabrutinib with glucocorticoids and (2) Active Comparator: glucocorticoids only.

Detailed Description
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4 weeks of screening, 12 weeks of main treatment, 12 weeks of cross-over (for GC-only group), 40 weeks of extension treatment and 4-week follow-up.

Official Title
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An Open Label, Two-Arm Study to Evaluate the Effect of Rilzabrutinib (PRN1008/SAR444671) on Safety and Disease Activity in Patients With IgG4-Related Disease

Conditions
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Immunoglobulin G4 Related Disease

Intervention / Treatment
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* Drug: rilzabrutinib
* Drug: Glucocorticoids


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Be male or female with age ≥18 years. Have a clinical diagnosis of IgG4-RD. Be willing to taper off an equivalent prednisone dose of between 20-40 mg/day in 2 weeks. Key Exclusion Criteria: Currently or within 6 months of screening taking rituximab, other B-cell depleting agents, or alkylating agents unless B cell concentrations have been demonstrated by flow cytometry to return to normal values (defined as 5 cells per cubic mm). History of solid organ transplant Positive at Screening for HIV, hepatitis B, hepatitis C, or TB Female patients who are pregnant or nursing. NOTE: Other Inclusion/Exclusion criteria may 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rilzabrutinib + glucocorticoids<br>Rilzabrutinib tablets, 400 mg twice daily from Week 0 to Week 12 plus glucocorticoids (20 to 40 mg/day prednisone equivalent tapered to 0 mg/day within 2 weeks on study) | Drug: rilzabrutinib<br>* oral tablet<br>* Other names: PRN1008/SAR444671;Drug: Glucocorticoids<br>* oral tablet or capsule<br>|
| Active Comparator: Glucocorticoids<br>Glucocorticoids (20 to 40 mg/day prednisone equivalent tapered to 0 mg/day within 12 weeks on study) | Drug: Glucocorticoids<br>* oral tablet or capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants who are without disease flare following the first dose of rilzabrutinib. | Disease flare is defined as an increase in IgG4-RD responder index (RI) >2 or initiation of rescue treatment. | At Week 52 | 
| Incidence of SAE, AE leading to discontinuation and possible glucocorticoid-related AE |  | Up to 68 weeks | 
| Number of participants with Potentially clinically significant abnormalities (PCSAs) for clinical laboratory tests, vital signs and ECG |  | Up to 68 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with reduction from baseline IgG4-RD RI activity score ≥2 points at Week 12 |  | At Week 52 | 
| Proportion of patients with an IgG4-RD RI activity score = 0 at Week 12 |  | At Week 52 | 
| Level and change from baseline of each subclass of the serological markers | serum protein electrophoresis to determine IgG subclasses and complement factors C3 and C4 | At Week 52 | 
| Proportion of participants achieving reduction in baseline serum IgG4 level of 10% at 12 weeks |  | At Week 12 | 
| Change from baseline in IgG4-RD RI over time |  | From baseline to Week 52 | 
| Proportion of participants with no disease flares between Week 4 and Week 12, and between Week 12 and Week 52 (or the end of the treatment extension period) among the participants who have treatment extension |  | Until Week 52 | 
| Change from baseline over time in IgG4-RD damage, as recorded on the damage portion of the IgG4-RD RI |  | From baseline to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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+IgG4, glucocorticoid, IgG4-RD, BTK, Bruton's