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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Immunoglobulin G4 Related Disease
• Intervention / Treatment: Drug: rilzabrutinib; Drug: Glucocorticoids

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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Trial Transparency email recommended (Toll free number for US & Canada); Phone Number: option 6 800-633-1610; Email: Contact-US@sanofi.com

Study Locations

• Canada
  • Vancouver, Canada, V6K 2V8
    • Investigational Site Number 12403
• France
  • Marseille, France
    • Investigational Site Number 25013
• Italy
  • Milan, Italy
    • Investigational Site Number 38016
• Spain
  • Barcelona, Spain
    • Investigational Site Number 72415
• United States
  • California
    • Stanford, California, United States, 94305
      • Investigational Site Number 84019
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Investigational Site Number 84016
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Investigational Site Number 84018
  • New York
    • New York, New York, United States, 10021
      • Investigational Site Number 84030
  • Oregon
    • Portland, Oregon, United States, 97239
      • Investigational Site Number 84036

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rilzabrutinib + 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)	Drug: rilzabrutinib; oral tablet; Other Names: PRN1008/SAR444671; Drug: Glucocorticoids; oral tablet or capsule
Active Comparator: Glucocorticoids; Glucocorticoids (20 to 40 mg/day prednisone equivalent tapered to 0 mg/day within 12 weeks on study)	Drug: Glucocorticoids; oral tablet or capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Disease flare is defined as an increase in IgG4-RD responder index (RI) >2 or initiation of rescue treatment.	At Week 52

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

Collaborators and Investigators

• Sponsor: Principia Biopharma, a Sanofi Company
• Collaborators: Massachusetts General Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2020
• Primary Completion (Estimated): August 30, 2024
• Study Completion (Estimated): September 27, 2024

Study Registration Dates

• First Submitted: August 11, 2020
• First Submitted That Met QC Criteria: August 17, 2020
• First Posted (Actual): August 20, 2020

Study Record Updates

• Last Update Posted (Actual): September 7, 2023
• Last Update Submitted That Met QC Criteria: September 6, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: glucocorticoid; BTK; IgG4-RD; +IgG4; Bruton's
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Immunoglobulin G4-Related Disease; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Glucocorticoids
• Other Study ID Numbers: ACT17125; PRN1008-017 (Other Identifier: Principia Biopharma); 2022-002959-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes