This is a parallel-group, Phase 3, double-blind, 2-arm study to investigate the efficacy, safety, PK and PD of oral rilzabrutinib in achieving durable Hb response (DHR) compared with placebo in approximately 90 male and female participants ≥ 18 years of age with a confirmed diagnosis of primary wAIHA.
Following a 4-week screening period, eligible participants will be randomized in a 2:1 ratio to receive rilzabrutinib or placebo in primary analysis period (PAP) for a duration of up to 24 weeks. All participants who completed PAP will then continue in open-label period (OLP) to receive rilzabrutinib for a duration of 28 weeks. Upon the completion of OLP, only participants who demonstrate Hb increase during the last 8 weeks of OLP per specified criteria in the protocol will be eligible to continue in long-term extension (LTE) of the study. The duration of the LTE period will be from the first-participant-in (FPI)-LTE until the last participant completes 52 weeks in LTE. The safety follow-up period of this study following treatment completion or discontinuation will be 2 weeks.
Male and female participants with a documented (confirmed) diagnosis of primary wAIHA for at least 6 months.
Participants who have previously failed to maintain a sustained response after treatment with CS (CS-resistance [defined as failure to obtain hemoglobin response within 3 weeks on at least 1 mg/kg or 60 mg prednisone or equivalent per day], CS-dependent wAIHA [defined as need to continue on prednisone or equivalent at a dose of >10 mg/day to maintain a response]), or are intolerant or ineligible to CS (defined as with contraindications, pre-existing medical conditions or CS-related complications that may render CS intolerant or ineligible per the best clinical judgement of the investigators).
Participants with Eastern Cooperative Oncology Group (ECOG) performance status Grade 2 or lower.
Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Participants with 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.
Participants with symptomatic herpes zoster within 3 months prior to screening.
Participants with mixed wAIHA, or secondary wAIHA from any cause including drugs, Evans Syndrome, 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.
Parallel
rilzabrutinib
DrugPharmaceutical form:tablet-Route of administration:oral
placebo
DrugPharmaceutical form:tablet-Route of administration:oral
Proportion of participants achieving DHR. DHR is defined as an increase of Hb by ≥2 g/dL from baseline on at least two thirds of evaluable scheduled visits between Week 12 and Week 24 (inclusive) in the PAP
DHR is defined as an increase of Hb by ≥2 g/dL from baseline on at least two thirds of evaluable scheduled visits between Week 12 and Week 24 (inclusive) in the PAP in the absence of rescue medication and transfusion.
Proportion of participants achieving overall Hb response (response [R] or complete response [CR]) by Week 24 of treatment in the PAP
Response is defined as an increase in Hb by ≥2 g/dL from baseline in the absence of transfusion and rescue medication. Complete Response is defined as Hb ≥12 g/dL (women) or ≥13 g/dL (men) without evidence of hemolysis (ie, normal indirect bilirubin, lactate dehydrogenase \[LDH\], haptoglobin, and reticulocytes), in the absence of transfusion and rescue medication.
Change from baseline in fatigue total score as measured by Functional Assessment of Chronic Illness Therapy (FACIT) - fatigue at Week 24
The time taken (days) to achieve the first Hb increase by ≥2 g/dL from baseline during the PAP in the previous 14 days and in the absence of rescue medication in the previous 6 weeks
Change from baseline in levels of LDH at Week 24
