The Efficacy and Safety of Rilzabrutinib in Participants Aged 10 to 65 Years With Sickle-cell Disease

NCT06975865 | Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: EFC178722024-518645-17U1111-1311-1896
• Study Type: interventional
• Target: 192
• Locations: 15 countries
• Sites: 54

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.

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (1)

• Annualized rate of clinical VOC

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

  At Week 52

Secondary Outcomes (10)

• 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

Study Arms (2)

Rilzabrutinib

EXPERIMENTAL

Rilzabrutinib

Drug: Rilzabrutinib

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Placebo DRUG

Pharmaceutical form:Tablet -Route of administration:Oral

Placebo

Rilzabrutinib DRUG

Pharmaceutical form:Tablet -Route of administration:Oral

Also known as: SAR444671

Rilzabrutinib

Eligibility Criteria

• Age: 10 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (54)

University of Alabama at Birmingham- Site Number : 8400003

Birmingham, Alabama, 35233, United States

RECRUITING

Phoenix Children's Hospital- Site Number : 8400028

Phoenix, Arizona, 85016, United States

RECRUITING

University of California San Francisco- Site Number : 8400040

Fresno, California, 93701, United States

RECRUITING

Oncology & Hematology Associates of West Broward- Site Number : 8400029

Coral Springs, Florida, 33065, United States

RECRUITING

Sylvester Comprehensive Cancer Center- Site Number : 8400020

Miami, Florida, 33136, United States

RECRUITING

University of Illinois-Chicago - College of Medicine- Site Number : 8400054

Chicago, Illinois, 60612, United States

RECRUITING

Indiana University Health Riley Hospital for Children- Site Number : 8400056

Indianapolis, Indiana, 46202, United States

RECRUITING

Louisiana State University Health Sciences Center - Shreveport- Site Number : 8400037

Shreveport, Louisiana, 71130, United States

RECRUITING

University of Maryland School of Medicine - Baltimore- Site Number : 8400041

Baltimore, Maryland, 21201, United States

RECRUITING

University of Michigan Health System - Ann Arbor- Site Number : 8400035

Ann Arbor, Michigan, 48109, United States

RECRUITING

Southern Specialty Research- Site Number : 8400059

Flowood, Mississippi, 39232, United States

RECRUITING

Richmond University Medical Center- Site Number : 8400038

Staten Island, New York, 10310, United States

RECRUITING

Baylor College of Medicine- Site Number : 8400055

Houston, Texas, 77030, United States

RECRUITING

VCU Massey Cancer Center: Dalton Oncology Clinic- Site Number : 8400012

Richmond, Virginia, 23298, United States

RECRUITING

Investigational Site Number : 0560003

Brussels, 1020, Belgium

RECRUITING

Investigational Site Number : 0560002

Brussels, 1070, Belgium

RECRUITING

Investigational Site Number : 0560001

Leuven, 3000, Belgium

RECRUITING

Hospital Santa Izabel- Site Number : 0760006

Salvador, Estado de Bahia, 40050-410, Brazil

RECRUITING

Universidade Federal de Goias- Site Number : 0760002

Goiânia, Goiás, 74605-020, Brazil

RECRUITING

Fundação Faculdade Regional de Medicina de São José do Rio Preto- Site Number : 0760001

São José do Rio Preto, São Paulo, 15090-000, Brazil

RECRUITING

Pontifícia Universidade Católica do Rio de Janeiro- Site Number : 0760009

Rio de Janeiro, 22451-900, Brazil

RECRUITING

Hospital Samaritano De Sao Paulo- Site Number : 0760005

São Paulo, 01232-010, Brazil

RECRUITING

Investigational Site Number : 2500002

Créteil, 94010, France

RECRUITING

Investigational Site Number : 2500005

Marseille, 13885, France

RECRUITING

Investigational Site Number : 2500001

Paris, 75015, France

RECRUITING

Investigational Site Number : 2500004

Toulouse, 31100, France

RECRUITING

Investigational Site Number : 2760002

Essen, 45147, Germany

RECRUITING

Investigational Site Number : 2760004

Stuttgart, 70736, Germany

RECRUITING

Investigational Site Number : 2880004

Kintampo, Ghana

ACTIVE NOT RECRUITING

Investigational Site Number : 2880002

Navrongo, UK-0043-7777, Ghana

ACTIVE NOT RECRUITING

Investigational Site Number : 3000001

Athens, 115 27, Greece

RECRUITING

Investigational Site Number : 3000003

Athens, 115 27, Greece

RECRUITING

Investigational Site Number : 3000002

Pátrai, 265 04, Greece

RECRUITING

Investigational Site Number : 3760001

Afula, 1834111, Israel

RECRUITING

Investigational Site Number : 3760002

Afula, 1834111, Israel

RECRUITING

Investigational Site Number : 3760005

Haifa, 3109601, Israel

RECRUITING

Investigational Site Number : 3760006

Haifa, 3109601, Israel

RECRUITING

Azienda Ospedaliero Universitaria Careggi SOD Ematologia-Site Number : 3800006

Florence, Firenze, 50134, Italy

RECRUITING

Investigational Site Number : 3800004

Milan, Milano, 20122, Italy

RECRUITING

Azienda Ospedaliera Universitaria, Università della Campania "Luigi Vanvitelli" Napoli-Site Number : 3800005

Naples, Napoli, 80138, Italy

RECRUITING

IRCCS Ospedale Pediatrico Bambino Gesù-Site Number : 3800001

Rome, Roma, 00165, Italy

RECRUITING

Azienda Ospedaliera Universitaria San Luigi Gonzaga, SSD Microcitemie Malattie Rare Ematologiche-Site Number : 3800007

Orbassano, Torino, 10043, Italy

RECRUITING

Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello-Site Number : 3800002

Palermo, 90146, Italy

RECRUITING

Centro Ricerche Cliniche Verona s.r.l. presso Ospedale G.B. Rossi Borgo Roma-Site Number : 3800003

Verona, 37134, Italy

RECRUITING

Investigational Site Number : 5280002

Rotterdam, 3015 CE, Netherlands

RECRUITING

Investigational Site Number : 5120001

Muscat, 123, Oman

RECRUITING

Investigational Site Number : 7240002

Madrid, 28007, Spain

RECRUITING

Investigational Site Number : 7240001

Madrid, 28046, Spain

RECRUITING

Investigational Site Number : 8340003

Mwanza, 1462, Tanzania

ACTIVE NOT RECRUITING

Investigational Site Number : 7920001

Adana, 01330, Turkey (Türkiye)

RECRUITING

Investigational Site Number : 7920002

Adana, 01330, Turkey (Türkiye)

RECRUITING

Investigational Site Number : 7920003

Mersin, 33330, Turkey (Türkiye)

RECRUITING

Investigational Site Number : 8260002

London, Harrow, NW10 7NS, United Kingdom

RECRUITING

Investigational Site Number : 8260001

London, London, City of, SE5 9RL, United Kingdom

RECRUITING

Related Links

• EFC17872 Plain Language Results Summary

MeSH Terms

Conditions

Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Central Study Contacts

Trial Transparency email recommended (Toll free for US & Canada)

CONTACT

800-633-1610; contact-us@sanofi.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2025
• First Posted: May 16, 2025
• Study Start: August 12, 2025
• Primary Completion (Estimated): July 23, 2027
• Study Completion (Estimated): December 29, 2028
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

BR (5); DE (2); US (14); NL (1); GH (2); GR (3); GB (2); FR (4); TU (3); IL (4); TA (1); OM (1); BE (3); IT (7); ES (2)