Clinical trial NCT06975865: The Efficacy and Safety of Rilzabrutinib in Patients Aged 10 to 65 Years With Sickle-cell Disease
Official title: A 52-week, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Group Sequential, Phase 3 Study to Evaluate the Efficacy and Safety of Rilzabrutinib in Patients Aged 10 to 65 Years With Sickle-cell Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Sickle Cell Disease
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2025-05-16
Enrollment: 192
Sex: ALL
Minimum age (years): 10
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Annualized rate of clinical VOC
timeFrame: At Week 52
Secondary outcomes:
measure: Time to first clinical VOC incidence
timeFrame: Until Week 52
measure: Annualized rate of visits due to SCD-related complications as assessed by the Investigator
timeFrame: At Week 52
measure: Annualized rate of home-managed VOCs as reported in the Sickle Cell Pain Crisis (SCPC) eDiary
timeFrame: At Week 52
measure: Change in fatigue as measured by the PROMIS SF v1.0 Fatigue 13a total score (adults)
timeFrame: From baseline to Week 52
measure: Change in Hb levels
timeFrame: From baseline to Week 52
measure: Change in fatigue as measured by the PedsQL Multidimensional Fatigue Scale total score (pediatric participants)
timeFrame: From baseline to Week 52
measure: Incidence of treatment emergent adverse events (TEAEs), including serious adverse events (SAEs), adverse events of special interest (AESIs) and adverse events leading to discontinuation
timeFrame: Until Week 52
measure: Incidence of potentially clinically significant laboratory, vital signs, and ECG abnormalities
timeFrame: Until Week 52
measure: Absolute number of simple and exchange blood transfusion
timeFrame: Until Week 52
measure: Number of days requiring acetaminophen, NSAID and/or short-acting opioid usage
timeFrame: Until Week 52
Other outcomes:
Locations:
city: Hialeah
country: United States
facility: Bioresearch Partners- Site Number : 8400005
state: Florida
city: London
country: United Kingdom
facility: Investigational Site Number : 8260002
Study officials:
References: