Rilzabrutinib for Immune Thrombocytopenia

(LUNA 3 Trial)

Recruiting at 272 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

232 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests rilzabrutinib, a drug that may help people with chronic ITP who have very low platelet counts. The drug works by blocking a substance that causes the immune system to destroy platelets. Participants will take the drug for several months to see if it helps increase their platelet levels.

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.

What data supports the effectiveness of the drug Rilzabrutinib for treating immune thrombocytopenia?

Research shows that Rilzabrutinib, a drug that blocks a specific protein involved in immune responses, can help increase platelet counts in people with immune thrombocytopenia by reducing platelet destruction and lowering harmful antibody production. In a study, 40% of patients experienced a positive platelet response, indicating its potential effectiveness. ^{1 2 3 4 5}

Is Rilzabrutinib safe for humans?

Rilzabrutinib has been studied in patients with immune thrombocytopenia and showed a well-tolerated safety profile with only mild, temporary side effects. ^{1 2 3 6 7}

How is the drug Rilzabrutinib different from other treatments for immune thrombocytopenia?

Rilzabrutinib is unique because it is an oral drug that works by inhibiting Bruton's tyrosine kinase, which helps reduce the destruction of platelets and the production of harmful antibodies. This dual mechanism of action sets it apart from other treatments that typically focus on either reducing platelet destruction or increasing platelet production. ^{1 2 8 9 10}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Rilzabrutinib, an Oral BTK Inhibitor, in Immune Thrombocytopenia. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Rilzabrutinib versus placebo in adults and adolescents with persistent or chronic immune thrombocytopenia: LUNA 3 phase III study. [2023]

3. Italy pubmed.ncbi.nlm.nih.gov

Comparison of up-front treatments for newly diagnosed immune thrombocytopenia -a systematic review and network meta-analysis. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Treatment patterns in adults with immune thrombocytopenia before, during and after use of thrombopoietin receptor agonists: a longitudinal prescription database study from Germany. [2022]

5. China pubmed.ncbi.nlm.nih.gov

[A clinical analysis of treatment with recombinant human thrombopoietin combined with large doses of dexamethasone in primary immune thrombocytopenia]. [2018]

6. Brazil pubmed.ncbi.nlm.nih.gov

Safety and efficacy of romiplostim in children and adolescents with Immune thrombocytopenia: A systematic review. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Rituximab therapy in adult patients with relapsed or refractory immune thrombocytopenic purpura: long-term follow-up results. [2015]

8. England pubmed.ncbi.nlm.nih.gov

Fostamatinib for the treatment of immune thrombocytopenia in adults. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Use and positioning of fostamatinib in the management of primary chronic immune thrombocytopenia: an Italian expert opinion. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Sustained response off therapy after fostamatinib: A chronic refractory ITP case report. [2023]