the efficacy and safety of rilzabrutinib in patients aged 10 to 65 years with sickle-cell disease

Conditions: Sickle Cell Disease

Summary: this is a phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group, group-sequential study (part a), followed by an open-label lte period (part b) to investigate the efficacy, and safety of rilzabrutinib in participants with sickle-cell disease (scd). study details include: * study duration: a 52-week double-blind period (part a), followed by an open-label lte period (part b). double-blind period has two parts, 50% (adult only) until the interim analysis, and 50% (adult and children) after the interim analysis. only the participants who complete double-blind treatment period (part a) are eligible to continue to the lte period. the duration of the lte period (part b) will be from the first-participant-in (fpi)-lte (part b) until the last participant who enters the lte has completed 52 weeks. * treatment duration: 52-week double-blind period (part a); lte period (part b) from the (fpi until the last participant who enters the lte has completed 52 weeks * visit frequency: week visits based on the schedule of assessments


Eligibility criteria:
inclusion criteria: * participants who have been diagnosed with scd. * participants who have had between ≥2 to ≤10 episodes of documented acute clinical voc within 12 months of the screening visit. * participants who are either not on hydroxyurea and/or l-glutamine at the screening visit and does not plan to receive them during the course of the study or has received hu and/or l-glutamine for a minimum of 6 months. participants on hydroxyurea and/or l-glutamine must have been on a stable weight-based dose level (mg/kg) for at least 3 months prior to the screening visit, with the intent to continue at the same weight-based dose level for the duration of the study, except for safety reasons. * 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. * for participants ≥10 to \<18 years of age: the parent(s)/legal guardian(s) must provide written informed consent prior to any study-related procedures being performed. exclusion criteria: * participants are excluded from the study if any of the following criteria apply: 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. * clinically relevant cardiac abnormality, in the opinion of the investigator or electrocardiogram (ecg) findings. * participants with history of stroke, or history of abnormal transcranial doppler. * participants with uncontrolled or active hbv infection and/or hcv infection including those receiving antiviral therapy at the time of screening. * hiv infection. * a history of active or latent tuberculosis (tb) * positive covid-19 molecular test. * participant is taking or has received crizanlizumab (adakveo®) within 90 days and/or voxelotor (oxbryta®) within 30 days prior to the screening visit. the above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.