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

Phase 2

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Rilzabrutinib + glucocorticoids	Glucocorticoids	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)
Glucocorticoids	Glucocorticoids	Glucocorticoids (20 to 40 mg/day prednisone equivalent tapered to 0 mg/day within 12 weeks on study)
Rilzabrutinib + glucocorticoids	rilzabrutinib	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)

Primary Outcome Measures

Name	Time	Method
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
Proportion of participants who are without disease flare following the first dose of rilzabrutinib.	At Week 52	Disease flare is defined as an increase in IgG4-RD responder index (RI) \>2 or initiation of rescue treatment.

Secondary Outcome Measures

Name	Time	Method
Proportion of patients with an IgG4-RD RI activity score = 0 at Week 12	At 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
Proportion of participants with reduction from baseline IgG4-RD RI activity score ≥2 points at Week 12	At Week 52
Level and change from baseline of each subclass of the serological markers	At Week 52	serum protein electrophoresis to determine IgG subclasses and complement factors C3 and C4
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
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

Locations (9): Investigational Site Number 84016
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Boston, Massachusetts, United States
Investigational Site Number 25013
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Marseille, France
Investigational Site Number 84019
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Stanford, California, United States
Investigational Site Number 84018
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Detroit, Michigan, United States
Investigational Site Number 84036
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Portland, Oregon, United States
Investigational Site Number 84030
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New York, New York, United States
Investigational Site Number 12403
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Vancouver, Canada
Investigational Site Number 38016
🇮🇹
Milan, Italy
Investigational Site Number 72415
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Barcelona, Spain