Sickle Cell Disease
Conditions
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.
Interventions
DRUGRilzabrutinib
Pharmaceutical form:Tablet -Route of administration:Oral
DRUGPlacebo
Pharmaceutical form:Tablet -Route of administration:Oral
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
10 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualized rate of clinical VOC | At Week 52 | Calculated from total number of clinical VOC incidents and total number of days during the observation period |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
Countries
Belgium, Brazil, France, Germany, Greece, Israel, Italy, Netherlands, Oman, Spain, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTTrial Transparency email recommended (Toll free for US & Canada)
Outcome results
None listed