A 52-week, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Flexible-adaptive, Group Sequential Study to Evaluate the Efficacy and Safety of Rilzabrutinib in Participants Aged 10 to 65 Years With Sickle-cell Disease

Sanofi84 sites in 13 countries192 target enrollmentAugust 12, 2025

InterventionsRilzabrutinib Placebo

DrugsRilzabrutinib Placebo

Overview

Phase: Phase 3
Intervention: Rilzabrutinib
Conditions: Not specified
Sponsor: Sanofi
Enrollment: 192
Locations: 84
Primary Endpoint: Annualized rate of clinical VOC
Status: Recruiting
Last Updated: yesterday

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, flexible-adaptive, 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 (a proof-concept part analogous to a phase 2b study), 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.

Registry

clinicaltrials.gov

Start Date

August 12, 2025

End Date

December 29, 2028

Last Updated

yesterday

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Sanofi

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Participants who have been diagnosed with SCD.
•Participants who have had between ≥2 and ≤10 episodes of documented clinical VOC within 12 months of the screening events.
•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.

Arms & Interventions

Rilzabrutinib

Intervention: Rilzabrutinib

Placebo

Intervention: Placebo

Outcomes

Primary Outcomes

Annualized rate of clinical VOC

Time Frame: At Week 52

Calculated from total number of clinical VOC incidents and total number of days during the observation period

Secondary Outcomes

Time to first clinical VOC incidence(Until Week 52)
Annualized rate of visits due to SCD-related complications as assessed by the Investigator(At Week 52)
Annualized rate of home-managed VOCs as reported in the Sickle Cell Pain Crisis (SCPC) eDiary(At Week 52)
Change in fatigue as measured by the PROMIS SF v1.0 Fatigue 13a total score (adults)(From baseline to Week 52)
Change in Hb levels(From baseline to Week 52)
Change in fatigue as measured by the PedsQL Multidimensional Fatigue Scale total score (pediatric participants)(From baseline to Week 52)
Incidence of treatment emergent adverse events (TEAEs), including serious adverse events (SAEs), adverse events of special interest (AESIs) and adverse events leading to discontinuation(Until Week 52)
Incidence of potentially clinically significant laboratory, vital signs, and ECG abnormalities(Until Week 52)
Absolute number of simple and exchange blood transfusion(Until Week 52)
Number of days requiring acetaminophen, NSAID and/or short-acting opioid usage(Until Week 52)