Clinical trial NCT04520451: Open Label Two-Arm Study to Evaluate Rilzabrutinib in IgG4-Related Disease Participants
Official title: An Open Label, Two-Arm Study to Evaluate the Effect of Rilzabrutinib (PRN1008/SAR444671) on Safety and Disease Activity in Participants With IgG4-Related Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Immunoglobulin G4 Related Disease
Keywords: +IgG4
glucocorticoid
IgG4-RD
BTK
Bruton's
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Massachusetts General Hospital
First posted: 2020-08-20
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of participants who are without disease flare following the first dose of rilzabrutinib until the end of treatment
timeFrame: Up to 64 weeks
measure: Incidence of SAE, AE leading to discontinuation and possible glucocorticoid-related AE
timeFrame: Up to 68 weeks
measure: Number of participants with Potentially clinically significant abnormalities (PCSAs) for clinical laboratory tests, vital signs and ECG
timeFrame: Up to 68 weeks
Secondary outcomes:
measure: Proportion of participants with reduction from baseline IgG4-RD RI activity score by ≥2 points over time
timeFrame: Up to 64 weeks
measure: Proportion of patients with an IgG4-RD RI activity score = 0 over time
timeFrame: Up to 64 weeks
measure: Level and change from baseline of each subclass of the serological markers over time
timeFrame: Up to 64 weeks
measure: Proportion of participants achieving reduction in baseline serum IgG4 level of 10% over time
timeFrame: Up to 64 weeks
measure: Change from baseline in IgG4-RD RI over time
timeFrame: From baseline up to 64 weeks
measure: Change from baseline over time in IgG4-RD damage, as recorded on the damage portion of the IgG4-RD RI over time
timeFrame: From baseline up to 64 weeks
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Investigational Site Number 84019
state: California
city: Boston
country: United States
facility: Investigational Site Number 84016
state: Massachusetts
city: Detroit
country: United States
facility: Investigational Site Number 84018
state: Michigan
city: New York
country: United States
facility: Investigational Site Number 84030
state: New York
city: Portland
country: United States
facility: Investigational Site Number 84036
state: Oregon
city: Vancouver
country: Canada
facility: Investigational Site Number 12403
city: Marseille
country: France
facility: Investigational Site Number 25013
city: Milan
country: Italy
facility: Investigational Site Number 38016
city: Barcelona
country: Spain
facility: Investigational Site Number 72415
Study officials:
References:
citation: Wallace ZS, Zhang Y, Perugino CA, Naden R, Choi HK, Stone JH; ACR/EULAR IgG4-RD Classification Criteria Committee. Clinical phenotypes of IgG4-related disease: an analysis of two international cross-sectional cohorts. Ann Rheum Dis. 2019 Mar;78(3):406-412. doi: 10.1136/annrheumdis-2018-214603. Epub 2019 Jan 5.