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

NCT04520451 | Completed Phase 2 DMC FDA Drug

• 4 other identifiers: ACT17125PRN1008-017U1111-1260-39722022-002959-18
• Study Type: interventional
• Target: 27
• Locations: 5 countries
• Sites: 9

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.

Conditions

Immunoglobulin G4 Related Disease

Keywords

+IgG4; glucocorticoid; IgG4-RD; BTK; Bruton's

Outcome Measures

Primary Outcomes (3)

• Proportion of participants who are without disease flare following the first dose of rilzabrutinib until the end of treatment

  Disease flare is defined as an increase in IgG4-RD responder index (RI) \>2 or initiation of rescue treatment.

  Up to 64 weeks

• 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 Outcomes (6)

• Proportion of participants with reduction from baseline IgG4-RD RI activity score by ≥2 points over time

  At Week 52

• Proportion of patients with an IgG4-RD RI activity score = 0 at over time

  Up to 64 weeks

• Level and change from baseline of each subclass of the serological markers over time

  Up to 64 weeks

• Proportion of participants achieving reduction in baseline serum IgG4 level of 10% over time

  Up to 64 weeks

• Change from baseline in IgG4-RD RI over time

  From baseline up to 64 weeks

Study Arms (2)

Rilzabrutinib + glucocorticoids

EXPERIMENTAL

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; Drug: Glucocorticoids

Glucocorticoids

ACTIVE COMPARATOR

Glucocorticoids (20 to 40 mg/day prednisone equivalent tapered to 0 mg/day within 12 weeks on study)

Drug: Glucocorticoids

Interventions

rilzabrutinib DRUG

oral tablet

Also known as: PRN1008/SAR444671

Rilzabrutinib + glucocorticoids

Glucocorticoids DRUG

oral tablet or capsule

Glucocorticoids; Rilzabrutinib + glucocorticoids

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Principia Biopharma, a Sanofi Company: lead
• Massachusetts General Hospital: collaborator

Study Sites (9)

Investigational Site Number 84019

Stanford, California, 94305, United States

Location

Investigational Site Number 84016

Boston, Massachusetts, 02114, United States

Location

Investigational Site Number 84018

Detroit, Michigan, 48202, United States

Location

Investigational Site Number 84030

New York, New York, 10021, United States

Location

Investigational Site Number 84036

Portland, Oregon, 97239, United States

Location

Investigational Site Number 12403

Vancouver, V6K 2V8, Canada

Location

Investigational Site Number 25013

Marseille, France

Location

Investigational Site Number 38016

Milan, Italy

Location

Investigational Site Number 72415

Barcelona, Spain

Location

Related Publications (1)

• 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.

  PMID: 30612117 BACKGROUND

MeSH Terms

Conditions

Immunoglobulin G4-Related Disease

Interventions

Glucocorticoids

Condition Hierarchy (Ancestors)

Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2020
• First Posted: August 20, 2020
• Study Start: August 22, 2020
• Primary Completion: October 15, 2024
• Study Completion: October 15, 2024
• Last Updated: October 14, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

IT (1); US (5); ES (1); FR (1); CA (1)