Clinical trial • Phase III • Immunology|Rare Disease

rilzabrutinib for Immunoglobulin G4-related disease

Phase III trial of rilzabrutinib for Immunoglobulin G4-related disease. Randomised, placebo (matching placebo); dose and schedule not specified-controlled.

Overview

Trial Therapeutic Area
Immunology|Rare Disease
Trial Disease
Immunoglobulin G4-related disease
Trial Stage
Phase III
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
14-07-2025
First CTIS Authorization Date
24-10-2025

Trial design

Randomised, placebo (matching placebo); dose and schedule not specified-controlled Phase III trial across 27 sites in Poland, Netherlands, Spain and others.

Randomised
Yes
Comparator
Placebo (matching placebo); dose and schedule not specified
Target Sample Size
94
Trial Duration For Participant
364

Eligibility

Recruits 94 No vulnerable populations selected (isVulnerablePopulationSelected: false). Trial enrols adults; informed consent is required from participants. Subject information and informed consent forms (SIS/ICF) and partner/pregnancy versions are provided in the submitted documentation in multiple languages..

Vulnerable Population
No vulnerable populations selected (isVulnerablePopulationSelected: false). Trial enrols adults; informed consent is required from participants. Subject information and informed consent forms (SIS/ICF) and partner/pregnancy versions are provided in the submitted documentation in multiple languages.

Inclusion criteria

  • {"criterion_text":"- Participants must have an adjudicated clinical diagnosis of IgG4-RD"}
  • {"criterion_text":"- Participants meeting Step 1 Entry criteria of 2019 ACR/EULAR classification criteria for IgG4-RD and Total inclusion points are ≥20"}
  • {"criterion_text":"- 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"}
  • {"criterion_text":"- Participants with history or current involvement of at least 1 organ/site (excluding lymph nodes) affected with IgG4-RD."}
  • {"criterion_text":"- Participants with active IgG4-RD controlled for at least 2 weeks while on a stable dose of GC"}
  • {"criterion_text":"- Participants willing to taper off GC after starting IMP."}
  • {"criterion_text":"- 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."}
  • {"criterion_text":"- 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."}
  • {"criterion_text":"- 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

  • {"criterion_text":"- Meet any Step 2 Exclusion criteria from the 2019 ACR/EULAR classification criteria for IgG4-RD."}
  • {"criterion_text":"- History of drug abuse within the previous 12 months."}
  • {"criterion_text":"- Alcoholism or excessive alcohol use, defined as regular consumption of more than approximately 3 standard drinks per day."}
  • {"criterion_text":"- Prior participation in any rilzabrutinib studies or other BTK inhibitor studies"}
  • {"criterion_text":"- History of treatment with an investigational drug within 6 months or 5 half- lives of the investigational drug, whichever is longer."}
  • {"criterion_text":"- Laboratory abnormalities at the screening visit identified by the central laboratory"}
  • {"criterion_text":"- History of retroperitoneal fibrosis, sclerosing mesenteritis, fibrosing mediastinitis, or other overwhelmingly fibrotic expression of IgG4-RD that is the sole disease manifestation."}
  • {"criterion_text":"- 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 non-metastatic squamous or basal cell carcinoma of the skin."}
  • {"criterion_text":"- 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."}
  • {"criterion_text":"- 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)."}
  • {"criterion_text":"- Current or chronic history of liver disease unrelated to IgG4-RD."}
  • {"criterion_text":"- Refractory nausea and vomiting, malabsorption, external biliary shunt, bariatric surgery, or significant bowel resection that would preclude adequate rilzabrutinib/placebo absorption."}
  • {"criterion_text":"- History of solid organ transplant."}
  • {"criterion_text":"- Planned major surgical procedure during the participation in this study."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Time to first adjudicated clinical disease flare treated by the investigator during the Blinded Treatment period","definition_or_measurement_approach":"Measured as time (duration) from baseline to the first adjudicated clinical disease flare that is treated by the investigator during the blinded treatment period."}

Secondary endpoints

  • {"endpoint_text":"- Percentage of participants without IgG4-RD adjudicated clinical disease flare and off glucocorticoids and immunomodulators","definition_or_measurement_approach":"Measured as the proportion (%) of participants with no adjudicated clinical disease flare and who are off glucocorticoids and immunomodulators at the assessment timepoint(s)."}
  • {"endpoint_text":"- Percentage of participants without IgG4-RD adjudicated clinical disease flare and off glucocorticoids","definition_or_measurement_approach":"Measured as the proportion (%) of participants with no adjudicated clinical disease flare and who are off glucocorticoids at the assessment timepoint(s)."}
  • {"endpoint_text":"- Annualized rate of clinical disease flares","definition_or_measurement_approach":"Calculated as the annualized incidence rate of adjudicated clinical disease flares per participant-year."}
  • {"endpoint_text":"- Change in IgG4-RD RI total activity scores from baseline to Week 52","definition_or_measurement_approach":"Change from baseline in the IgG4-RD Responder Index total activity score at Week 52."}
  • {"endpoint_text":"- Percent change in IgG4-RD RI total activity scores form baseline to Week 52","definition_or_measurement_approach":"Percent change from baseline in IgG4-RD RI total activity score at Week 52."}
  • {"endpoint_text":"- Change in IgG4-RD RI total activity scores from baseline to Week 12","definition_or_measurement_approach":"Change from baseline in IgG4-RD RI total activity score at Week 12."}
  • {"endpoint_text":"- Proportion of participants with reduction of ≥2 points from the baseline IgG4-RD RI total activity score","definition_or_measurement_approach":"Proportion (%) of participants achieving a reduction of ≥2 points in the IgG4-RD RI total activity score from baseline at specified timepoints."}
  • {"endpoint_text":"- Proportion of participants in complete remission","definition_or_measurement_approach":"Proportion (%) of participants meeting protocol-defined criteria for complete remission at specified timepoints."}
  • {"endpoint_text":"- Cumulative glucocorticoid dose for treatment of IgG4-RD","definition_or_measurement_approach":"Total cumulative dose of glucocorticoids administered for IgG4-RD treatment over the assessment period."}
  • {"endpoint_text":"- Proportion of participants with potentially clinically significant abnormalities in laboratory tests, vital signs, and electrocardiograms in the Safety Population","definition_or_measurement_approach":"Proportion (%) of participants with predefined clinically significant abnormalities in labs, vital signs, or ECGs in the safety population."}
  • {"endpoint_text":"- Proportion of participants with TEAEs, AESIs, SAEs in the Safety Population","definition_or_measurement_approach":"Proportion (%) of participants experiencing treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs), and serious adverse events (SAEs) in the safety population."}

Recruitment

Digital Remote Recruitment
Yes
Planned Sample Size
94
Recruitment Window Months
65
Consent Approach
Informed consent obtained from adult participants using provided subject information and informed consent forms (SIS/ICF). SIS/ICF documents and partner/pregnancy versions are available in multiple languages (English, French, Spanish, Italian, Dutch, Polish, Swedish, German). No assent procedures (adults only).

Methods

  • Posters and printed recruitment materials (country-specific posters listed: e.g., PL, ES, IT, FR, NL, SV, DE) distributed at participating hospitals/clinics
  • Advertisements (print/online) - country-specific recruitment advertisements submitted (files labelled advertisement per country)
  • Brochures for patients (country-specific) provided at sites
  • Social media caption (Italy) — K2-recruitment-material-social-caption-it indicates social media channels may be used
  • GP letters and other site-to-GP informational materials (Italy) — L2-other-subject-information-material-gp-letter-it
  • Sponsor-to-doctor materials (Italy) — K2-recruitment-material-sponsor-to-dr-it

Geography

Total Number Of Sites
27
Total Number Of Participants
50

Poland

Earliest CTIS Part Ii Submission Date
06-10-2025
Latest Decision Or Authorization Date
07-11-2025
Processing Time Days
32
Number Of Sites
3
Number Of Participants
5

Sites

Site Name
Uniwersyteckie Centrum Kliniczne
Department Name
Centrum Wsparcia Badan Klinicznych UCK Osrodek Badan Wczesnych Faz
Contact Person Name
Anna Masiak
Contact Person Email
anna.masiak@gumed.edu.pl
Site Name
Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu
Department Name
Oddzial Kliniczny Reumatologii i Chorob Wewnetrznych
Contact Person Name
Piotr Wiland
Contact Person Email
pwiland1@gmail.com
Site Name
Malopolskie Badania Kliniczne Sp. z o.o.
Department Name
Malopolskie Badania Kliniczne sp. z. o.o
Contact Person Name
Bogdan Batko
Contact Person Email
bpbatko@gmail.com

Netherlands

Earliest CTIS Part Ii Submission Date
06-10-2025
Latest Decision Or Authorization Date
27-10-2025
Processing Time Days
21
Number Of Sites
2
Number Of Participants
3

Sites

Site Name
Universitair Medisch Centrum Groningen
Department Name
Department of Rheumatology and Clinical Immunology
Contact Person Name
Abraham Rutgers
Contact Person Email
a.rutgers@umcg.nl
Site Name
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Department Name
EMCR, Section Immunology, Department of internal Medicine
Contact Person Name
Jan Van Laar
Contact Person Email
j.vanlaar@erasmusmc.nl

Spain

Earliest CTIS Part Ii Submission Date
08-10-2025
Latest Decision Or Authorization Date
30-10-2025
Processing Time Days
22
Number Of Sites
3
Number Of Participants
5

Sites

Site Name
Hospital De La Santa Creu I Sant Pau
Department Name
Servicio de Reumatología
Contact Person Name
Patricia Moya Alvarado
Contact Person Email
pmoyaa@santpau.cat
Site Name
Hospital Universitari Vall D Hebron
Department Name
Servicio de Medicina Interna
Contact Person Name
Fernando Martinez-Valle
Site Name
Hospital Universitario Ramon Y Cajal
Department Name
Servicio de Medicina Interna
Contact Person Name
Andres Gonzalez Garcia

Italy

Earliest CTIS Part Ii Submission Date
06-10-2025
Latest Decision Or Authorization Date
07-11-2025
Processing Time Days
32
Number Of Sites
3
Number Of Participants
5

Sites

Site Name
Ospedale San Raffaele S.r.l.
Department Name
San Raffaele Hospital Oncologia
Contact Person Name
Lorenzo Dagna
Contact Person Email
dagna.trials@hsr.it
Site Name
Azienda Ospedaliera Universitaria Meyer IRCCS
Department Name
Azienda Ospedaliero Universitaria Meyer
Contact Person Name
Augusto Vaglio
Contact Person Email
augusto.vaglio@meyer.it
Site Name
Centro Ricerche Cliniche Di Verona S.r.l.
Department Name
Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Roma Neurologia
Contact Person Name
Luca Frulloni
Contact Person Email
luca.frulloni@univr.it

Sweden

Earliest CTIS Part Ii Submission Date
06-10-2025
Latest Decision Or Authorization Date
07-11-2025
Processing Time Days
32
Number Of Sites
2
Number Of Participants
3

Sites

Site Name
Karolinska University Hospital
Department Name
Gastroenerology
Contact Person Name
Miroslav Vujasinovic
Site Name
Uppsala University Hospital
Department Name
Rheumatology
Contact Person Name
Lilian Vasaitis
Contact Person Email
lilian.vasaitis@akademiska.se

France

Earliest CTIS Part Ii Submission Date
28-07-2025
Latest Decision Or Authorization Date
24-10-2025
Processing Time Days
88
Number Of Sites
7
Number Of Participants
12

Sites

Site Name
Hospital Foch
Department Name
Hôpital Foch
Contact Person Name
Matthieu Groh
Contact Person Email
m.groh@hopital-foch.com
Site Name
Centre Hospitalier Universitaire De Bordeaux
Department Name
Centre Hospitalier Universitaire de Bordeaux - Groupe Hospitalier Sud - Hôpital Haut Lévêque
Contact Person Name
Jean-Francois VIALLARD
Site Name
Centre Hospitalier Universitaire De Dijon
Department Name
Hôpital François Mitterrand Service de Pneumologie
Contact Person Name
Sylvain Audia
Contact Person Email
sylvain.audia@chu-dijon.fr
Site Name
Centre Hospitalier Regional De Marseille
Department Name
Hôpital La Timone Medecine interne
Contact Person Name
Nicolas Schleinitz
Contact Person Email
Nicolas.SCHLEINITZ@ap-hm.fr
Site Name
Hopital Beaujon
Department Name
AP-HP - Hopital Beaujon
Contact Person Name
Vinciane Rebours
Contact Person Email
vinciane.rebours@aphp.fr
Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Hôpital Claude Huriez service de médecine interne
Contact Person Name
Emmanuel Ledoult
Contact Person Email
emmanuel.ledoult2@chu-lille.fr
Site Name
Hospices Civils De Lyon
Department Name
Hôpital de la Croix-Rousse Service de Pneumologie
Contact Person Name
Gaëlle RICHARD-COLMANT

Belgium

Earliest CTIS Part Ii Submission Date
28-07-2025
Latest Decision Or Authorization Date
24-10-2025
Processing Time Days
88
Number Of Sites
1
Number Of Participants
5

Sites

Site Name
UZ Leuven
Department Name
UZ Leuven - Gasthuisberg Campus
Contact Person Name
Steven Vanderschueren

Germany

Earliest CTIS Part Ii Submission Date
16-10-2025
Latest Decision Or Authorization Date
07-11-2025
Processing Time Days
22
Number Of Sites
6
Number Of Participants
12

Sites

Site Name
Medizinische Hochschule Hannover
Department Name
Medizinische Hochschule Hannover (Hannover Medical School) Klinik für Rheumatologie und Immunologie
Contact Person Name
Torsten Witte
Contact Person Email
witte.torsten@mh-hannover.de
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Charité-Campus Virchow-Klinikum
Contact Person Name
Toni Herta
Contact Person Email
toni.herta@charite.de
Site Name
Universitaetsklinikum Erlangen AöR
Department Name
Medizin 3 - Studienambulanz
Contact Person Name
Andreas Ramming
Contact Person Email
andreas.ramming@uk-erlangen.de
Site Name
Johannes Wesling Klinikum Minden
Department Name
Klinik für Rheumatologie und klinische Immunologie
Contact Person Name
Gunter Assmann
Site Name
Universitaetsklinikum Ulm AöR
Department Name
Department of Internal Medicine Division of Interdisciplinary Pancreatology
Contact Person Name
Alexandra Kleger
Contact Person Email
alexander.kleger@uni-ulm.de
Site Name
Martin-Luther-Universitaet Halle-Wittenberg
Department Name
Universitätsklinik und Poliklinik für Innere Medizin I
Contact Person Name
Jonas Rosendahl
Contact Person Email
jonas.rosendahl@uk-halle.de

Sponsor

Primary sponsor

Full Name
Sanofi-Aventis Recherche & Developpement
Organisation Type
Pharmaceutical company
Country Of Registered Address
France

Contract research organisations

Name
Suvoda LLC
Name
Eresearchtechnology Inc.
Responsibilities
Patient Responded Outcome
Name
ESMS Global Limited
Responsibilities
Centralized 24-Hour Emergency System: eSMS

Third parties

  • {"country":"Poland","full_name":"Centrala Farmaceutyczna Cefarm S.A.","duties_or_roles":"sponsorDuties codes: [14]","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"ESMS Global Limited","duties_or_roles":"Centralized 24-Hour Emergency System: eSMS","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Massachusetts General Hospital","duties_or_roles":"PRO","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Patient Responded Outcome","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"Poland","full_name":"Centrala Farmaceutyczna Cefarm S.A.","duties_or_roles":"sponsorDuties codes: [14]","organisation_type":"Pharmaceutical company"}
  • {"country":"Italy","full_name":"Depo-pack S.r.l.","duties_or_roles":"sponsorDuties codes: [14]","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
rilzabrutinib (SAR444671)
Active Substance
rilzabrutinib
Modality
Small molecule
Investigational Product Name
Placebo
Modality
Other

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