Rilzabrutinib for Sickle Cell Disease

(LIBRA Trial)

Recruiting at 43 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Sanofi

Must be taking: Hydroxyurea, L-glutamine

Must not be taking: Crizanlizumab, Voxelotor

Disqualifiers: Lymphoma, Leukemia, Stroke, HIV, 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: Unknown

Duration: 52 weeks

192 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called rilzabrutinib for individuals with sickle cell disease (SCD). The goal is to evaluate its effectiveness and safety for patients who frequently experience painful episodes known as vaso-occlusive crises (2 to 10 times a year). Participants should have SCD and either not be on certain other medications or be stable on them for at least three months. The trial involves taking the treatment or a placebo (a non-active substance) for a year, with regular check-ins to monitor progress. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for SCD.

Will I have to stop taking my current medications?

If you are taking hydroxyurea or L-glutamine, you can continue them at a stable dose during the study. However, if you are taking crizanlizumab or voxelotor, you must stop them before joining the trial.

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

Research has shown that rilzabrutinib was safe in earlier studies. It was tested in individuals with immune thrombocytopenia (ITP), where it was well-tolerated and improved platelet levels. This suggests rilzabrutinib could be safe for humans.

Additionally, rilzabrutinib has received orphan drug status for sickle cell disease, indicating promising evidence of its safety and potential benefits. However, while these early results are encouraging, ongoing studies are essential to confirm the safety of rilzabrutinib specifically for sickle cell disease. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sickle cell disease?

Rilzabrutinib is unique because it targets Bruton’s tyrosine kinase (BTK), a mechanism not typically addressed by current sickle cell disease treatments. While most treatments focus on managing pain or increasing red blood cell count, Rilzabrutinib aims to reduce inflammation and improve blood flow by inhibiting BTK. This approach could potentially offer a new way to alleviate the complications of sickle cell disease, sparking excitement among researchers for its innovative action in tackling the disease's underlying issues.

What evidence suggests that rilzabrutinib might be an effective treatment for sickle cell disease?

Research suggests that rilzabrutinib, which participants in this trial may receive, may help treat sickle cell disease. Studies in mice have shown that this drug can reduce blood vessel blockages, a major issue in sickle cell disease. Rilzabrutinib also decreases inflammation and improves blood flow by reducing cell adhesion. Although limited data exist on its effects in humans with sickle cell disease, these findings indicate that rilzabrutinib might improve symptoms related to blood flow and inflammation. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for patients aged 10 to 65 with Sickle-cell Disease who've had 2-10 acute clinical VOC episodes in the past year. They should have an ECOG status of ≤2, use contraception, and either not be on hydroxyurea/L-glutamine or have been on a stable dose for at least 6 months.

Inclusion Criteria

I have been diagnosed with sickle cell disease.

I've had 2 to 10 episodes of acute pain crises in the last year.

I am following local guidelines for contraception while in this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either rilzabrutinib or placebo during a 52-week double-blind period

52 weeks

Weekly visits based on the Schedule of Assessments

Open-label extension (LTE)

Participants who complete the double-blind period may continue to receive rilzabrutinib in an open-label extension

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Rilzabrutinib

Trial Overview The study tests Rilzabrutinib's effectiveness and safety against a placebo in SCD patients over a year. It starts with a double-blind phase where neither doctors nor participants know who gets the drug or placebo, followed by an open-label period where everyone knows.

How Is the Trial Designed?

Group I: Rilzabrutinib Experimental Treatment 1 Intervention

Rilzabrutinib

Group II: Placebo Placebo Group 1 Intervention

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. clinicaltrials.gov clinicaltrials.gov/study/NCT06975865

NCT06975865 | The Efficacy and Safety of Rilzabrutinib in ... ... efficacy, and safety of rilzabrutinib in participants with sickle-cell disease (SCD). Study details include: Study duration: a 52-week double-blind period ...

2. sanofi.com sanofi.com/en/media-room/press-releases/2025/2025-06-03-05-00-00-3092429

Press Release: Rilzabrutinib granted orphan drug ... Preclinical data on sickle cell disease was presented at ASH 2024 showing that rilzabrutinib helped reduce vaso-occlusion –blockage of blood ...

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

Efficacy and Safety Results With Rilzabrutinib, an Oral ... Nine (35%) patients achieved the primary endpoint. Platelet counts ≥ 50 × 109/L or ≥ 30 × 109/L and doubling from baseline without rescue ...

4. hematologyadvisor.com hematologyadvisor.com/news/rilzabrutinib-designated-orphan-drug-for-sickle-cell-disease/

Rilzabrutinib Designated Orphan Drug for Sickle Cell ... Preclinical findings show the drug reduces vaso-occlusion, markers of inflammation, and adhesion in transgenic mice with sickle cell disease.

5. hematology.org hematology.org/newsroom/press-releases/2024/researchers-report-new-opportunities-to-improve-quality-of-life

Researchers Report New Opportunities to Improve Quality ... Secondary endpoints revealed that participants treated with rilzabrutinib showed improvements in platelet counts, fatigue, and bleeding, and a ...

6. clinicaladvisor.com clinicaladvisor.com/news/rilzabrutinib-designated-orphan-drug-for-sickle-cell-disease/

Rilzabrutinib Designated Orphan Drug for Sickle Cell ... The safety and efficacy of rilzabrutinib in patients with sickle cell disease will be evaluated in the phase 3 LIBRA trial (ClinicalTrials.gov ...

7. sanofistudies.com sanofistudies.com/cwout/CW-V9DEXS//gb/en/listing/313062/the-efficacy-and-safety/

The Efficacy and Safety of Rilzabrutinib in Patients Clinical Studies for Sickle Cell Disease , The Efficacy and Safety of Rilzabrutinib in Patients Aged 10 to 65 Years With Sickle-cell Disease.