Rilzabrutinib for Immunoglobulin-Related Disease

(RILIEF Trial)

Recruiting at 14 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Sanofi

Must be taking: GC

Disqualifiers: Active malignancy, Immunodeficiency, Liver disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 25

Duration: 52 weeks

124 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how well rilzabrutinib, a new potential drug, works for people with IgG4-RD, a condition where the immune system causes inflammation in various body parts. The study will determine if this treatment can prevent flare-ups and control the disease better than a placebo over a year. It also assesses the treatment's safety by monitoring side effects. Adults with active IgG4-RD affecting at least one organ and managing it with stable steroid doses might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially bringing a new treatment to market.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that participants should be willing to taper off glucocorticoids (a type of steroid) after starting the study medication. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that rilzabrutinib is likely to be safe for humans?

Research shows that rilzabrutinib has been tested for safety in treating IgG4-related disease. In earlier studies, most participants tolerated rilzabrutinib well. Common side effects included diarrhea in 23% of participants, nausea in 17%, headache in 8%, and stomach pain in 6%. These side effects occurred more frequently than in those who took a placebo, a harmless pill used for comparison.

Rilzabrutinib has also been safe for individuals with other conditions, such as immune thrombocytopenic purpura, a bleeding disorder. This suggests that the treatment might be safe for humans, although some may experience mild to moderate side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for IgG4-RD?

Rilzabrutinib is unique because it targets Bruton's tyrosine kinase (BTK), a key player in the immune system's response, which is different from most treatments for immunoglobulin-related diseases that usually focus on suppressing symptoms. This new mechanism allows Rilzabrutinib to potentially modulate the immune system more precisely, reducing unwanted immune reactions without broadly weakening the body's defenses. Researchers are excited about this treatment because it could offer a more effective and safer option, with fewer side effects than current therapies.

What evidence suggests that rilzabrutinib might be an effective treatment for IgG4-RD?

Research has shown that rilzabrutinib, which participants in this trial may receive, can help reduce flare-ups in people with IgG4-related disease (IgG4-RD). In one study, patients who took rilzabrutinib experienced fewer flare-ups and showed improvement in other important health markers. These improvements occurred quickly and lasted a long time, aiding in better control of the condition. The treatment targets specific proteins involved in the disease, helping to manage symptoms and reduce flare-ups. This suggests that rilzabrutinib could be a promising option for those with IgG4-RD. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

Adults with active IgG4-related Disease (IgG4-RD) who are willing to undergo imaging tests like CT, MRI, PET, or ultrasound. They must have a history of the disease affecting at least one organ and be able to control it with stable doses of glucocorticoids (GC). Participants should agree to taper off GC after starting the study medication and be up-to-date on vaccinations.

Inclusion Criteria

I meet the criteria for IgG4-related disease with a score of 20 or more.

My vaccinations are up-to-date according to local guidelines.

I am following local guidelines for contraception during this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4-6 weeks

Treatment

Participants receive rilzabrutinib or placebo tablets in a double-blind manner to assess efficacy and safety over a 52-week period

52 weeks

16 visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term with rilzabrutinib

108 weeks

9 visits

What Are the Treatments Tested in This Trial?

Interventions

• Rilzabrutinib

Trial Overview The trial is testing Rilzabrutinib's effectiveness compared to a placebo in treating IgG4-RD over 52 weeks. It will measure time until disease flare-up, flare-free rate, control of disease activity, need for additional GC treatment, and safety through adverse events monitoring and lab tests including ECGs.

How Is the Trial Designed?

Group I: Rilzabrutinib Experimental Treatment 2 Interventions

Rilzabrutinib

Group II: Placebo Placebo Group 2 Interventions

Placebo

Who Is Running the Clinical Trial?

Sanofi

Lead Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Citations

1. sanofi.com sanofi.com/en/media-room/press-releases/2025/2025-06-12-08-30-00-3098093

Media Update: EULAR: rilzabrutinib data in IgG4-related ... New data from a phase 2 study showed that treatment with rilzabrutinib led to a considerable reduction in disease flares and other key disease markers.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07190196

NCT07190196 | A 52-week Study of Rilzabrutinib Efficacy ... 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 IgG ...

3. rarediseaseadvisor.com rarediseaseadvisor.com/news/study-compare-safety-efficacy-rilzabrutinib-vs-placebo-igg4-rd/

New Study Will Compare Safety, Efficacy of Rilzabrutinib vs ... A 52-week study of rilzabrutinib efficacy and safety compared to placebo in adults diagnosed with IgG4-related disease (RILIEF). ClinicalTrials.

4. ashpublications.org ashpublications.org/blood/article/145/24/2914/536104/Safety-and-efficacy-of-rilzabrutinib-vs-placebo-in

Safety and efficacy of rilzabrutinib vs placebo in adults with ... Treatment with rilzabrutinib resulted in statistically and clinically meaningful improvements in all aspects of the disease, including rapid and durable ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12427540/

Evaluating rilzabrutinib in the treatment of immune ... Data from clinical studies showed that rilzabrutinib, when taken twice a day, increased platelet count levels rapidly and for long periods. Additionally, ...

6. sanofi.com sanofi.com/assets/dotcom/pressreleases/2025/2025-06-12-08-30-00-3098093-en.pdf

EULAR: rilzabrutinib data in IgG4-related disease show ... New data from a phase 2 study showed that treatment with rilzabrutinib led to a considerable reduction in disease flares and other key disease ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39844469/

Efficacy and Safety Results With Rilzabrutinib, an Oral ... Rilzabrutinib continues to demonstrate durable platelet responses with favorable safety profile in previously treated ITP patients.