A 52-week study of rilzabrutinib efficacy and safety compared to placebo in adults diagnosed with IgG4-related disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

4 Dec 2025 → ongoing

Decision date (initial)

2025-10-24

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2025-521398-15-00

WHO UTN

U1111-1316-0266

ClinicalTrials.gov

NCT07190196

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy, Pharmacodynamic, Therapy, Pharmacogenetic

To assess the efficacy of rilzabrutinib compared to placebo in prolonging flare-free period in
participants with active IgG4-RD

Secondary objectives 4

1. To evaluate clinical disease flare-free rate
2. To assess the effect of rilzabrutinib compared to placebo on control of disease activity
3. To assess need for glucocorticoids to maintain disease control in both treatment arms
4. To evaluate the safety and tolerability in both treatment arms

Conditions and MedDRA coding

Immune system diseases

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share 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

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Participants must have an adjudicated clinical diagnosis of IgG4-RD
2. Participants meeting Step 1 Entry criteria of 2019 ACR/EULAR classification criteria for IgG4-RD and Total inclusion points are ≥20
3. 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
4. Participants with history or current involvement of at least 1 organ/site (excluding lymph nodes) affected with IgG4-RD.
5. Participants with active IgG4-RD controlled for at least 2 weeks while on a stable dose of GC
6. Participants willing to taper off GC after starting IMP.
7. 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.
8. 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.
9. 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 14

1. Meet any Step 2 Exclusion criteria from the 2019 ACR/EULAR classification criteria for IgG4-RD.
2. History of retroperitoneal fibrosis, sclerosing mesenteritis, fibrosing mediastinitis, or other overwhelmingly fibrotic expression of IgG4-RD that is the sole disease manifestation.
3. 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.
4. 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.
5. 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).
6. Current or chronic history of liver disease unrelated to IgG4-RD.
7. Refractory nausea and vomiting, malabsorption, external biliary shunt, bariatric surgery, or significant bowel resection that would preclude adequate rilzabrutinib/placebo absorption.
8. History of solid organ transplant.
9. Planned major surgical procedure during the participation in this study.
10. History of drug abuse within the previous 12 months.
11. Alcoholism or excessive alcohol use, defined as regular consumption of more than approximately 3 standard drinks per day.
12. Prior participation in any rilzabrutinib studies or other BTK inhibitor studies
13. History of treatment with an investigational drug within 6 months or 5 half- lives of the investigational drug, whichever is longer.
14. Laboratory abnormalities at the screening visit identified by the central laboratory

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to first adjudicated clinical disease flare treated by the investigator during the Blinded Treatment period

Secondary endpoints 11

1. Percentage of participants without IgG4-RD adjudicated clinical disease flare and off glucocorticoids and immunomodulators
2. Percentage of participants without IgG4-RD adjudicated clinical disease flare and off glucocorticoids
3. Annualized rate of clinical disease flares
4. Change in IgG4-RD RI total activity scores from baseline to Week 52
5. Percent change in IgG4-RD RI total activity scores form baseline to Week 52
6. Change in IgG4-RD RI total activity scores from baseline to Week 12
7. Proportion of participants with reduction of ≥2 points from the baseline IgG4-RD RI total activity score
8. Proportion of participants in complete remission
9. Cumulative glucocorticoid dose for treatment of IgG4-RD
10. Proportion of participants with potentially clinically significant abnormalities in laboratory tests, vital signs, and electrocardiograms in the Safety Population
11. Proportion of participants with TEAEs, AESIs, SAEs in the Safety Population

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

13 Quai Jules Guesde

City

Vitry Sur Seine

Postcode

94400

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Third parties 10

Locations

8 EU/EEA countries · 27 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 71 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications