Rilzabrutinib for Immune Thrombocytopenia

(LUNA 3 Trial)

Not currently recruiting at 321 trial locations

Overseen By Sibel Ucpinar

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Principia Biopharma, a Sanofi Company

Must not be taking: Immunosuppressants, Rituximab, BTK inhibitors

Disqualifiers: Secondary ITP, Pregnancy, Malignancy, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests rilzabrutinib, a new treatment, to determine its effectiveness for individuals with Immune Thrombocytopenia (ITP), a condition that causes low platelet counts and can lead to easy bruising or bleeding. The study compares rilzabrutinib to a placebo to assess its effectiveness and safety over several months. It seeks participants who have had ITP for over six months (or three months for adults) and experienced a temporary increase in platelet counts from previous treatments like IVIg (immune globulin therapy) but did not maintain those levels. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

The trial requires that you do not change your dose of corticosteroids (CS) or thrombopoietin receptor agonists (TPO-RA) within 14 days before starting the study. You also cannot take immunosuppressant drugs other than CSs within a certain period before the study. It's best to discuss your current medications with the study team to see if any adjustments are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that rilzabrutinib is generally safe for treating immune thrombocytopenia (ITP). Common side effects include mild to moderate issues such as diarrhea, nausea, headache, and stomach pain. These side effects occurred more frequently in patients taking rilzabrutinib than in those taking a placebo. Importantly, most side effects were not serious, and no major safety concerns have been reported. This suggests that patients usually tolerate rilzabrutinib well. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ITP?

Unlike the standard treatments for immune thrombocytopenia, such as corticosteroids and immunoglobulins, Rilzabrutinib targets the condition with a unique mechanism. It is a Bruton tyrosine kinase (BTK) inhibitor, which works by modulating the immune system to prevent the destruction of platelets. This targeted approach potentially offers a more precise intervention, reducing the broad immune suppression seen with current therapies. Researchers are excited about Rilzabrutinib because it might provide effective treatment with fewer side effects and a more favorable safety profile compared to existing options.

What evidence suggests that rilzabrutinib might be an effective treatment for immune thrombocytopenia?

In this trial, participants will receive either rilzabrutinib or a placebo. A previous study showed that rilzabrutinib quickly and effectively increased platelet counts in patients with immune thrombocytopenia (ITP). Research has shown that about 40% of patients experienced lasting improvement in their platelet levels. This treatment also reduced the need for additional medications and decreased bleeding episodes. Additionally, patients reported feeling less physically tired while taking rilzabrutinib. Overall, rilzabrutinib appears to be both effective and safe for treating ITP. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

Adults and adolescents with persistent or chronic immune thrombocytopenia (ITP) who have a very low platelet count are eligible for this trial. They must not be pregnant, planning surgery soon, or have had certain treatments like blood transfusions recently. Participants need to agree to use contraception and cannot have other health conditions that might interfere with the study.

Inclusion Criteria

My child needs treatment for ITP as decided by our doctor.

All contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Your blood platelet count has been consistently low, and no single platelet count has been higher than 35,000/µL in the last 14 days before starting the study drug.

Exclusion Criteria

Pregnant or lactating women

I haven't changed my CS or TPO-RA dose significantly in the last 14 days.

I am scheduled for surgery during the treatment period.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 4 weeks

Blinded Treatment

Participants receive rilzabrutinib or placebo 400mg twice daily

12 to 24 weeks

Open-Label Period

Participants receive open-label rilzabrutinib

28 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term Extension

Participants may opt into continuation of treatment long-term

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Rilzabrutinib

Trial Overview The trial is testing Rilzabrutinib, a potential new treatment for ITP. Patients will either receive Rilzabrutinib or a placebo twice daily over several weeks to see if it helps increase their platelet counts compared to no active treatment.

How Is the Trial Designed?

Group I: Rilzabrutinib Experimental Treatment 1 Intervention

Patients receive rilzabrutinib 400mg orally twice daily for up to 24 weeks followed by 28 weeks of open label period

Group II: Placebo Placebo Group 1 Intervention

Patients receive matching placebo 400mg orally twice daily for up to 24 weeks

Who Is Running the Clinical Trial?

Principia Biopharma, a Sanofi Company

Lead Sponsor

Trials

10

Recruited

670+

Published Research Related to This Trial

In a phase 1-2 clinical trial involving 60 patients with immune thrombocytopenia, rilzabrutinib demonstrated a platelet response in 40% of participants, indicating its efficacy in increasing platelet counts through dual mechanisms of action.

The treatment was well-tolerated, with only low-level, transient side effects and no serious bleeding or thrombotic events, suggesting a favorable safety profile for further testing at the identified effective dose of 400 mg twice daily.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rilzabrutinib, an Oral BTK Inhibitor, in Immune Thrombocytopenia. Kuter, DJ., Efraim, M., Mayer, J., et al.[2022]

Fostamatinib is an oral spleen tyrosine kinase inhibitor that effectively increases platelet counts in adults with immune thrombocytopenia who did not respond adequately to previous treatments, as shown in two Phase III trials.

The treatment is generally well tolerated, with lower rates of severe bleeding-related side effects, although common adverse events include diarrhea, nausea, and liver function test elevations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fostamatinib for the treatment of immune thrombocytopenia in adults. Moore, DC., Gebru, T., Muslimani, A.[2021]

Fostamatinib, a recently approved SYK-inhibitor for chronic immune thrombocytopenia, showed a complete response in a patient who had previously failed multiple treatments, indicating its efficacy in difficult cases.

This case is notable as it demonstrates that fostamatinib can be safely discontinued after achieving a sustained response, with the patient's platelet count remaining stable even after reducing and stopping the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustained response off therapy after fostamatinib: A chronic refractory ITP case report. Auteri, G., Biondo, M., Mazzoni, C., et al.[2023]

Citations

1. 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 ... Rilzabrutinib in patients who failed multiple previous ITP therapies showed rapid and durable platelet response, reduced rescue medication and bleeding, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04562766

NCT04562766 | Study to Evaluate Rilzabrutinib in Adults ... This is a randomized, double-blind study of rilzabrutinib in patients with persistent or chronic ITP, with an average platelet count of <30,000/μL (and no ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12134720/

Rilzabrutinib for the Treatment of Immune Thrombocytopenia Results from the phase 1/2 LUNA 2 trial and its long‐term extension demonstrated that Rilzabrutinib induced a durable platelet response in 40% of patients, with ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2110297

Rilzabrutinib, an Oral BTK Inhibitor, in Immune ... Overall, treatment with oral rilzabrutinib led to rapid and durable clinical activity in 40% of these patients with immune thrombocytopenia, who ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0006497125006081

Safety and efficacy of rilzabrutinib vs placebo in adults with ... Rilzabrutinib had rapid and durable platelet response, reduced rescue use and bleeding, improved physical fatigue, and favorable safety.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03395210

NCT03395210 | A Study of Rilzabrutinib in Adult Patients ... This is a 2 part (Part A and B) adaptive, open-label, dose-finding study of PRN1008 in patients with ITP who are refractory or relapsed with no available ...