Efficacy, Safety and Pharmacokinetics of Rilzabrutinib in Patients With Warm Autoimmune Hemolytic Anemia (wAIHA)

This is a single group treatment, Phase 2, open-label, study to evaluate the efficacy, safety and pharmacokinetics of rilzabrutinib in adult patients with wAIHA.

All participants will receive rilzabrutinib orally. The screening period is up to 28 days, followed by a treatment period of 24 weeks for Part A. Participants who complete Part A and are deemed eligible for Part B will continue to receive the study medication for 52 weeks following the Last Patient In (LPI-Part B). There will be a 7-day safety follow-up period after receiving the last dose of study drug either in Part A (for those not eligible for Part B or early terminated) or Part B. Participants in Part B can continue to receive the study intervention until the LPI-Part B has completed 52 weeks of treatment.

The long-term extension period (Part B) will include two parts: the Core Part B period that will last until the last participant completes 52 weeks in Core Part B and an Extended Part B period following the completion of Core Part B. Each participant will attend an EOT-Core Part B visit when the last participant completes 52 weeks in Part B. Following completion of the Core Part B, eligible participants may continue in the Extended Part B until the study medication becomes commercially available in the study participant's country, or the study medication is no longer being developed by the Sponsor for wAIHA indication, the program is stopped for safety reasons and the Sponsor decides to stop the study.


Eligibility Criteria:
Inclusion Criteria:

* Male and female patients with a confirmed diagnosis of primary wAIHA or systemic lupus erythematosus (SLE)-associated wAIHA (without other SLE-related manifestations apart from cutaneous and musculoskeletal manifestations)
* Participants who have previously failed to maintain a sustained response after treatment with corticosteroids.
* Eastern Cooperative Oncology Group (ECOG) performance status grade 2 or lower.
* Up-to-date vaccination status as per local guidelines.
* Body mass index (BMI) \>17.5 and \<40 kg/m2
* All contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Core Part B

* Evidence of treatment efficacy to rilzabrutinib as defined by achieving overall response during Part A.
* Completion of Part A treatment period (24 weeks). Extended Part B
* Completion of Core Part B period.

Exclusion Criteria:

* Clinically significant medical history or ongoing chronic illness that would jeopardize the safety of the participant or compromise the quality of the data derived from his or her participation in the study as determined by the Investigator.
* Participants with medical history of lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for the past 3 years.
* Secondary wAIHA from any cause including drugs, lymphoproliferative disorders (low-count monoclonal B-cell lymphocytosis is allowed), infectious or autoimmune disease, or active hematologic malignancies. Participants with positive antinuclear antibodies but without a definitive diagnosis of an autoimmune disease are allowed.
* Myelodysplastic syndrome.
* Uncontrolled or active HBV infection: Patients with positive HBsAg and/or HBV DNA.
* HIV infection.
* Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days or 5 half-lives, whichever is greater, prior to treatment start.
* Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.

Part B only

* Participants who receive any therapy during Part A known to be active in wAIHA.
* Presence of unacceptable side effect(s) or toxicity associated with rilzabrutinib such that there is an unfavorable risk-benefit assessment for continued treatment with rilzabrutinib in the opinion of the Investigator and/or Sponsor.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.