A 52-week Study of Rilzabrutinib Efficacy and Safety Compared to Placebo in Adults Diagnosed With IgG4-related Disease (RILIEF)

June 1, 2026 updated by: Sanofi

A Randomized, Phase 3, Double-blind, 52-week Study to Evaluate the Efficacy and Safety of Rilzabrutinib (SAR444671) Compared to Placebo in Adult Participants With Active IgG4-related Disease

This is a Phase 3, parallel group, 2-arm, randomized, double blind, placebo-controlled, 52-week treatment study to assess the efficacy and safety of rilzabrutinib as a treatment for adult patients with active IgG4-RD.

The purpose of this study is to measure time to IgG4-RD clinical disease flare, and other relevant efficacy endpoints including flare-free rate, control of IgG4-RD disease activity, use of GC rescue and safety parameters such as treatment-emergent adverse events, clinical laboratory values and electrocardiograms (ECG) in participants aged 18 years and above, diagnosed with IgG4-RD and treated with rilzabrutinib tablets over a 52-week placebo-controlled period.

Study details include:

The study duration will be up to 60 weeks, including a 4 to 6-week screening period, a 52-week double blind treatment period, and 2 weeks of follow up (plus an optional OLE of 108 weeks).

The number of visits will be 16 (plus an optional 9 visits during the OLE).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

124

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

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

Study Locations

  • Argentina
      • Buenos Aires, Argentina, 1015
        • Recruiting
        • Investigational Site Number : 0320004
    • Buenos Aires
      • Berazategui, Buenos Aires, Argentina, 1886
        • Recruiting
        • Investigational Site Number : 0320005
      • San Isidro, Buenos Aires, Argentina, B1643CRO
        • Recruiting
        • Investigational Site Number : 0320003
    • Chaco Province
      • Resistencia, Chaco Province, Argentina, 3500
        • Recruiting
        • Investigational Site Number : 0320002
  • Belgium
      • Leuven, Belgium, 3000
        • Recruiting
        • Investigational Site Number : 0560001
  • Canada
    • Quebec
      • Sherbrooke, Quebec, Canada, J1G 2E8
        • Recruiting
        • Investigational Site Number : 1240001
  • Chile
    • Biobio
      • Concepción, Biobio, Chile, 4070038
        • Recruiting
        • Investigational Site Number : 1520005
    • Reg Metropolitana de Santiago
      • Santiago, Reg Metropolitana de Santiago, Chile, 8330032
        • Recruiting
        • Investigational Site Number : 1520002
      • Santiago, Reg Metropolitana de Santiago, Chile, 8207257
        • Recruiting
        • Investigational Site Number : 1520006
      • Santiago, Reg Metropolitana de Santiago, Chile, 8320325
        • Recruiting
        • Investigational Site Number : 1520001
      • Santiago, Reg Metropolitana de Santiago, Chile, 7500504
        • Recruiting
        • Centro de estudios G y C-Site Number : 1520003
        • Principal Investigator:
          • Ivan Gonzalez
        • Contact:
  • China
      • Beijing, China, 100730
        • Recruiting
        • Investigational Site Number : 1560001
      • Beijing, China, 100034
        • Recruiting
        • Investigational Site Number : 1560008
      • Beijing, China, 100050
        • Recruiting
        • Investigational Site Number : 1560004
      • Chengdu, China, 610041
        • Recruiting
        • Investigational Site Number : 1560012
      • Hangzhou, China, 310009
        • Recruiting
        • Investigational Site Number : 1560010
      • Jiazhuang, China, 050000
        • Recruiting
        • Investigational Site Number : 1560003
      • Taiyuan, China, 030001
        • Recruiting
        • Investigational Site Number : 1560013
      • Taiyuan, China, 030032
        • Recruiting
        • Investigational Site Number : 1560005
      • Wuhan, China, 430030
        • Recruiting
        • Investigational Site Number : 1560011
      • Yantai, China, 264001
        • Recruiting
        • Investigational Site Number : 1560009
  • France
      • Clichy, France, 92110
        • Active, not recruiting
        • AP-HP - Hôpital Beaujon-Site Number : 2500002
      • Marseille, France, 13885
        • Recruiting
        • Investigational Site Number : 2500001
      • Pessac, France, 33600
        • Active, not recruiting
        • CHU Bordeaux - Hôpital Haut Leveque-Site Number : 2500003
  • Germany
      • Berlin, Germany, 13353
        • Recruiting
        • Investigational Site Number : 2760001
      • Erlangen, Germany, 91054
        • Recruiting
        • Investigational Site Number : 2760003
      • Minden, Germany, 32429
        • Recruiting
        • Investigational Site Number : 2760004
      • Ulm, Germany, 89081
        • Recruiting
        • Investigational Site Number : 2760006
  • Israel
    • Central District
      • Petah Tikva, Central District, Israel, 4941492
        • Recruiting
        • Rabin MC, Outpatient Clinics Building-Site Number : 3760001
        • Contact:
        • Principal Investigator:
          • Elisheva Pokroy Shapira
      • Tel Aviv, Central District, Israel, 6423906
        • Recruiting
        • Sourasky Rheumatology Dept, Rishonim Building-Site Number : 3760005
        • Contact:
        • Principal Investigator:
          • Yael Lahat Goldstein
  • Italy
    • Firenze
      • Florence, Firenze, Italy, 50139
        • Recruiting
        • AOU Meyer IRCCS-Site Number : 3800003
        • Contact:
        • Contact:
        • Principal Investigator:
          • Prof. Augusto Vaglio
    • Lombardy
      • Milan, Lombardy, Italy, 20132
        • Recruiting
        • IRCCS Ospedale San Raffaele-Site Number : 3800001
        • Contact:
        • Principal Investigator:
          • Prof. Lorenzo Dagna
    • Veneto
      • Verona, Veneto, Italy, 37134
        • Recruiting
        • Centro Ricerche Cliniche di Verona s.r.l. c/o Policlinico G.B.Rossi-Site Number : 3800002
        • Contact:
        • Principal Investigator:
          • Prof. Luca Frulloni
        • Contact:
  • Japan
      • Tokyo, Japan, 160-8582
        • Recruiting
        • Investigational Site Number : 3920009
    • Hiroshima
      • Hiroshima, Hiroshima, Japan, 734-8551
        • Recruiting
        • Hiroshima University Hospital-Site Number : 3920007
        • Principal Investigator:
          • Shintaro Hirata
        • Contact:
    • Hokkaido
      • Sapporo, Hokkaido, Japan, 060-8543
        • Recruiting
        • Investigational Site Number : 3920011
    • Ishikawa-ken
      • Kahoku, Uchinada, Ishikawa-ken, Japan, 920-0293
        • Recruiting
        • Kanazawa Medical University Hospital-Site Number : 3920002
        • Principal Investigator:
          • Yasufumi Masaki
        • Contact:
      • Kanazawa, Ishikawa-ken, Japan, 920-8641
        • Recruiting
        • Investigational Site Number : 3920001
    • Osaka
      • Hirakata, Osaka, Japan, 573-1191
        • Recruiting
        • Investigational Site Number : 3920003
    • Tokyo
      • Bunkyo-ku, Tokyo, Japan, 113-8677
        • Recruiting
        • Investigational Site Number : 3920008
      • Minato-ku, Tokyo, Japan, 108-8639
        • Recruiting
        • The Institute of Medical Science, The University of Tokyo-Site Number : 3920006
        • Contact:
        • Principal Investigator:
          • Motohisa Yamamoto
  • Netherlands
      • Groningen, Netherlands, 9713 GZ
        • Active, not recruiting
        • UMCG-Site Number : 5280002
    • South Holland
      • Rotterdam, South Holland, Netherlands, 3015 GD
        • Active, not recruiting
        • Erasmus Medisch Centrum-Site Number : 5280001
  • Poland
    • Lesser Poland Voivodeship
      • Krakow, Lesser Poland Voivodeship, Poland, 30-002
        • Recruiting
        • Malopolskie Badania Kliniczne sp. z. o.o.-Site Number : 6160001
        • Principal Investigator:
          • Bogdan Batko
        • Contact:
    • Lower Silesian Voivodeship
      • Wroclaw, Lower Silesian Voivodeship, Poland, 50-556
        • Recruiting
        • Investigational Site Number : 6160002
    • Pomeranian Voivodeship
      • Gdansk, Pomeranian Voivodeship, Poland, 80-214
        • Recruiting
        • Uniwersyteckie Centrum Kliniczne, Centrum Wsparcia Badan Klinicznych UCK Osrodek Badan Wczesnych Faz-Site Number : 6160003
        • Contact:
        • Principal Investigator:
          • Anna Masiak
  • Saudi Arabia
      • Riyadh, Saudi Arabia, 12713
        • Recruiting
        • Investigational Site Number : 6820001
      • Riyadh, Saudi Arabia, 12372
        • Recruiting
        • Investigational Site Number : 6820002
  • South Korea
    • Gyeonggi-do
      • Suwon, Gyeonggi-do, South Korea, 16499
        • Recruiting
        • Investigational Site Number : 4100002
    • Seoul-teukbyeolsi
      • Seoul, Seoul-teukbyeolsi, South Korea, 03080
        • Recruiting
        • Investigational Site Number : 4100001
  • Spain
      • Madrid, Spain, 28034
        • Recruiting
        • Investigational Site Number : 7240004
    • Barcelona [Barcelona]
      • Barcelona, Barcelona [Barcelona], Spain, 08035
        • Recruiting
        • Investigational Site Number : 7240001
    • Catalunya [Cataluña]
      • Barcelona, Catalunya [Cataluña], Spain, 08041
        • Recruiting
        • Investigational Site Number : 7240002
  • Sweden
      • Huddinge, Sweden, 141 57
        • Recruiting
        • Investigational Site Number : 7520001
      • Uppsala, Sweden, 751 85
        • Recruiting
        • Investigational Site Number : 7520002
  • Taiwan
      • Kaohsiung City, Taiwan, 833
        • Recruiting
        • Investigational Site Number : 1580004
      • Taipei, Taiwan, 10016
        • Recruiting
        • Investigational Site Number : 1580001
      • Taoyuan City, Taiwan, 333
        • Recruiting
        • Investigational Site Number : 1580002
  • United Kingdom
    • Norfolk
      • Norwich, Norfolk, United Kingdom, NR4 7UY
        • Recruiting
        • Investigational Site Number : 8260004
  • United States
    • California
      • Fontana, California, United States, 92335
        • Recruiting
        • Kaiser Permanente - Fontana Medical Center- Site Number : 8400015
      • San Jose, California, United States, 95128
        • Recruiting
        • San Jose Clinical Trials- Site Number : 8400016
        • Contact:
        • Principal Investigator:
          • Slawomir Wojtowicz-Praga
      • Tustin, California, United States, 92780
        • Recruiting
        • Solace Clinical Research - Tustin- Site Number : 8400020
        • Principal Investigator:
          • Roger Kornu
        • Contact:
    • Florida
      • Margate, Florida, United States, 33063
        • Recruiting
        • Life Clinical Trials - Margate - Colonial Drive- Site Number : 8400002
        • Principal Investigator:
          • Jigar Shah
        • Contact:
      • Miami, Florida, United States, 33136
        • Recruiting
        • Schiff Center for Liver Diseases- Site Number : 8400010
      • Palm Beach Gardens, Florida, United States, 33410
        • Recruiting
        • Vitalia Medical Research - Margate- Site Number : 8400025
        • Principal Investigator:
          • Clifford Stermer
        • Contact:
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory University School of Medicine - Atlanta- Site Number : 8400013
      • Fayetteville, Georgia, United States, 30214
        • Recruiting
        • Primeway Clinical Research- Site Number : 8400019
        • Contact:
        • Principal Investigator:
          • Charlita Worthy
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital- Site Number : 8400008
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic in Rochester - Minnesota- Site Number : 8400017
        • Contact:
        • Principal Investigator:
          • Motaz Ashkar
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic - Cleveland- Site Number : 8400001
        • Contact:
        • Principal Investigator:
          • James Fernandez
      • Columbus, Ohio, United States, 43215
        • Recruiting
        • Ohio State University Wexner Medical Center- Site Number : 8400024
      • Middleburg Heights, Ohio, United States, 44140
        • Recruiting
        • Paramount Medical Research and Consulting LLC- Site Number : 8400018
        • Principal Investigator:
          • Isam Diab
        • Contact:
    • Texas
      • Plano, Texas, United States, 75093
        • Recruiting
        • Stryde Research- Site Number : 8400011
        • Contact:
        • Principal Investigator:
          • Rahul Patel
      • Red Oak, Texas, United States, 75154
        • Recruiting
        • Epic Medical Research - Red Oak- Site Number : 8400003
        • Principal Investigator:
          • Sunny Patel
        • Contact:
      • Wichita Falls, Texas, United States, 76301
        • Recruiting
        • Digestive Health Research of North Texas- Site Number : 8400021
        • Contact:
        • Principal Investigator:
          • Vanya Wagler
    • Washington
      • Seattle, Washington, United States, 98105
        • Recruiting
        • Velocity Clinical Research - Seattle- Site Number : 8400005
        • Principal Investigator:
          • Kris Kowdley
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Participants must have an adjudicated clinical diagnosis of IgG4-RD
  • Participants meeting Step 1 Entry criteria of 2019 ACR/EULAR classification criteria for IgG4-RD and Total inclusion points are ≥20
  • Participants with active disease at screening in at least one organ system, excluding lymph nodes, as an IgG4-RD Responder Index total activity score ≥ 2
  • Participants with history or current involvement of at least 1 organ/site (excluding lymph nodes) affected with IgG4-RD.
  • Participants with active IgG4-RD controlled for at least 2 weeks while on a stable dose of GC.
  • Participants willing to taper off GC after starting IMP.
  • Participants willing and able to participate in repeated study protocol mandated or clinically indicated imaging procedures to assess IgG4-RD such as computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), or ultrasound.
  • Participants who have an up-to-date vaccination status as per local guidelines. The last dose of live vaccines should be received at least 30 days before Day 1.
  • Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Exclusion Criteria:

  • Meet any Step 2 Exclusion criteria from the 2019 ACR/EULAR classification criteria for IgG4-RD.
  • History of retroperitoneal fibrosis, sclerosing mesenteritis, fibrosing mediastinitis, or other overwhelmingly fibrotic expression of IgG4-RD that is the sole disease manifestation.
  • Active malignancy or history of malignancy within 5 years before Day 1, except completely treated in situ carcinoma of the cervix, completely treated, and resolved nonmetastatic squamous or basal cell carcinoma of the skin.
  • Known or suspected immunodeficiency, including history of invasive opportunistic infections (eg, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, and aspergillosis) despite infection resolution, or otherwise recurrent infections of abnormal frequency or prolonged duration suggesting an immune compromised status, as judged by the Investigator.
  • History of serious infections with the potential for recurrence (as judged by the Investigator), with less than 4 weeks interval between resolution of serious infection and first dose of study drug, or currently active moderate to severe infection at Screening (Grade 2 or higher).
  • Current or chronic history of liver disease unrelated to IgG4-RD.
  • Refractory nausea and vomiting, malabsorption, external biliary shunt, bariatric surgery, or significant bowel resection that would preclude adequate rilzabrutinib/placebo absorption.
  • History of solid organ transplant.
  • Planned major surgical procedure during the participation in this study.
  • History of drug abuse within the previous 12 months.
  • Alcoholism or excessive alcohol use, defined as regular consumption of more than approximately 3 standard drinks per day.
  • Prior participation in any rilzabrutinib studies or other BTK inhibitor studies.
  • History of treatment with an investigational drug within 6 months or 5 half-lives of the investigational drug, whichever is longer.
  • Laboratory abnormalities at the screening visit identified by the central laboratory The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Glucocorticoid
Pharmaceutical form:Tablet, solution, suspension formulations according to local standard practices-Route of administration:Oral
Drug: Placebo
Pharmaceutical form:Tablet-Route of administration:Oral
Experimental: Rilzabrutinib
Drug: Rilzabrutinib
Pharmaceutical form:Tablet-Route of administration:Oral
Other Names:
  • SAR444671
Drug: Glucocorticoid
Pharmaceutical form:Tablet, solution, suspension formulations according to local standard practices-Route of administration:Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to first adjudicated clinical disease flare treated by the investigator during the Blinded Treatment period
Time Frame: Until Week 52
The Adjudication Committee will include internationally recognized independent experts in diagnosis and management of patients with IgG4-RD, blinded to participant, investigator, and site identifiers
Until Week 52

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of participants without IgG4-RD adjudicated clinical disease flare and off glucocorticoids and immunomodulators
Time Frame: At Week 52
At Week 52
Percentage of participants without IgG4-RD adjudicated clinical disease flare and off glucocorticoids
Time Frame: At Week 52
At Week 52
Annualized rate of clinical disease flares
Time Frame: At Week 52
At Week 52
Proportion of participants with reduction of ≥2 points from the baseline IgG4-RD RI total activity score
Time Frame: At Week 12, Week 24, and Week 52
At Week 12, Week 24, and Week 52
Cumulative glucocorticoid dose for treatment of IgG4-RD
Time Frame: At Week 52
At Week 52
Proportion of participants with potentially clinically significant abnormalities in laboratory tests, vital signs, and electrocardiograms in the Safety Population
Time Frame: Until Week 160
Until Week 160
Proportion of participants with TEAEs, AESIs, SAEs in the Safety Population
Time Frame: Until Week 160
Until Week 160
Change in IgG4-RD RI total activity scores from baseline to Week 52
Time Frame: From baseline to Week 52
From baseline to Week 52
Percent change in IgG4-RD RI total activity scores form baseline to Week 52
Time Frame: From baseline to Week 52
From baseline to Week 52
Change in IgG4-RD RI total activity scores from baseline to Week 12
Time Frame: From baseline to Week 12
From baseline to Week 12
Proportion of participants in complete remission
Time Frame: At Week 52
Defined by an IgG4-RD RI total activity score = 0 or absence of evident disease activity assessed by the Investigator
At Week 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sanofi

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 26, 2025

Primary Completion (Estimated)

June 28, 2028

Study Completion (Estimated)

December 25, 2030

Study Registration Dates

First Submitted

September 17, 2025

First Submitted That Met QC Criteria

September 17, 2025

First Posted (Actual)

September 24, 2025

Study Record Updates

Last Update Posted (Actual)

June 2, 2026

Last Update Submitted That Met QC Criteria

June 1, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EFC17359
  • U1111-1316-0266 (Registry Identifier: WHO ICTRP)
  • 2025-521398-15 (Registry Identifier: CTIS)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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