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

July 28, 2026 updated by: Sanofi

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

192

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Trial Transparency email recommended (Toll free for US & Canada)
  • Phone Number: option 6 800-633-1610
  • Email: contact-us@sanofi.com

Study Locations

  • Belgium
      • Brussels, Belgium, 1020
        • Recruiting
        • Investigational Site Number : 0560003
      • Brussels, Belgium, 1070
        • Recruiting
        • Investigational Site Number : 0560002
      • Leuven, Belgium, 3000
        • Recruiting
        • Investigational Site Number : 0560001
  • Brazil
      • Rio de Janeiro, Brazil, 22451-900
        • Recruiting
        • Pontifícia Universidade Católica do Rio de Janeiro- Site Number : 0760009
      • São Paulo, Brazil, 01232-010
        • Recruiting
        • Hospital Samaritano De Sao Paulo- Site Number : 0760005
    • Estado de Bahia
      • Salvador, Estado de Bahia, Brazil, 40050-410
        • Recruiting
        • Hospital Santa Izabel- Site Number : 0760006
    • Goiás
      • Goiânia, Goiás, Brazil, 74605-020
        • Recruiting
        • Universidade Federal de Goias- Site Number : 0760002
    • São Paulo
      • São José do Rio Preto, São Paulo, Brazil, 15090-000
        • Recruiting
        • Fundação Faculdade Regional de Medicina de São José do Rio Preto- Site Number : 0760001
  • France
      • Créteil, France, 94010
        • Recruiting
        • Investigational Site Number : 2500002
      • Marseille, France, 13885
        • Recruiting
        • Investigational Site Number : 2500005
      • Paris, France, 75015
        • Recruiting
        • Investigational Site Number : 2500001
      • Toulouse, France, 31100
        • Recruiting
        • Investigational Site Number : 2500004
  • Germany
      • Essen, Germany, 45147
        • Recruiting
        • Investigational Site Number : 2760002
      • Stuttgart, Germany, 70736
        • Recruiting
        • Investigational Site Number : 2760004
  • Greece
      • Athens, Greece, 115 27
        • Recruiting
        • Investigational Site Number : 3000001
      • Athens, Greece, 115 27
        • Recruiting
        • Investigational Site Number : 3000003
      • Pátrai, Greece, 265 04
        • Recruiting
        • Investigational Site Number : 3000002
  • Israel
      • Afula, Israel, 1834111
        • Recruiting
        • Investigational Site Number : 3760002
      • Afula, Israel, 1834111
        • Recruiting
        • Investigational Site Number : 3760001
      • Haifa, Israel, 3109601
        • Recruiting
        • Investigational Site Number : 3760005
      • Haifa, Israel, 3109601
        • Recruiting
        • Investigational Site Number : 3760006
  • Italy
      • Palermo, Italy, 90146
        • Recruiting
        • Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello-Site Number : 3800002
        • Contact:
        • Contact:
        • Principal Investigator:
          • Rosario Di Maggio
      • Verona, Italy, 37134
        • Recruiting
        • Centro Ricerche Cliniche Verona s.r.l. presso Ospedale G.B. Rossi Borgo Roma-Site Number : 3800003
        • Contact:
        • Principal Investigator:
          • Lucia De Franceschi
    • Firenze
      • Florence, Firenze, Italy, 50134
        • Recruiting
        • Azienda Ospedaliero Universitaria Careggi SOD Ematologia-Site Number : 3800006
        • Contact:
        • Contact:
        • Principal Investigator:
          • Valentina Carrai
    • Milano
      • Milan, Milano, Italy, 20122
        • Recruiting
        • Investigational Site Number : 3800004
    • Napoli
      • Naples, Napoli, Italy, 80138
        • Recruiting
        • Azienda Ospedaliera Universitaria, Università della Campania "Luigi Vanvitelli" Napoli-Site Number : 3800005
        • Principal Investigator:
          • Silverio Perrotta
        • Contact:
        • Contact:
    • Roma
      • Rome, Roma, Italy, 00165
        • Recruiting
        • IRCCS Ospedale Pediatrico Bambino Gesù-Site Number : 3800001
        • Principal Investigator:
          • Franco Locatelli
        • Contact:
    • Torino
      • Orbassano, Torino, Italy, 10043
        • Recruiting
        • Azienda Ospedaliera Universitaria San Luigi Gonzaga, SSD Microcitemie Malattie Rare Ematologiche-Site Number : 3800007
        • Contact:
        • Contact:
        • Principal Investigator:
          • Vincenzo Voi
  • Netherlands
      • Rotterdam, Netherlands, 3015 CE
        • Recruiting
        • Investigational Site Number : 5280002
  • Oman
      • Muscat, Oman, 123
        • Recruiting
        • Investigational Site Number : 5120001
  • Spain
      • Madrid, Spain, 28046
        • Recruiting
        • Investigational Site Number : 7240001
      • Madrid, Spain, 28007
        • Recruiting
        • Investigational Site Number : 7240002
  • Turkey (Türkiye)
      • Adana, Turkey (Türkiye), 01330
        • Recruiting
        • Investigational Site Number : 7920001
      • Adana, Turkey (Türkiye), 01330
        • Recruiting
        • Investigational Site Number : 7920002
      • Mersin, Turkey (Türkiye), 33330
        • Recruiting
        • Investigational Site Number : 7920003
  • United Kingdom
    • Harrow
      • London, Harrow, United Kingdom, NW10 7NS
        • Recruiting
        • Investigational Site Number : 8260002
    • London, City of
      • London, London, City of, United Kingdom, SE5 9RL
        • Recruiting
        • Investigational Site Number : 8260001
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Recruiting
        • University of Alabama at Birmingham- Site Number : 8400003
    • Arizona
      • Phoenix, Arizona, United States, 85016
        • Recruiting
        • Phoenix Children's Hospital- Site Number : 8400028
    • California
      • Fresno, California, United States, 93701
        • Recruiting
        • University of California San Francisco- Site Number : 8400040
    • Florida
      • Coral Springs, Florida, United States, 33065
        • Recruiting
        • Oncology & Hematology Associates of West Broward- Site Number : 8400029
      • Miami, Florida, United States, 33136
        • Recruiting
        • Sylvester Comprehensive Cancer Center- Site Number : 8400020
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Recruiting
        • University of Illinois-Chicago - College of Medicine- Site Number : 8400054
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Indiana University Health Riley Hospital for Children- Site Number : 8400056
    • Louisiana
      • Shreveport, Louisiana, United States, 71130
        • Recruiting
        • Louisiana State University Health Sciences Center - Shreveport- Site Number : 8400037
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Recruiting
        • University of Maryland School of Medicine - Baltimore- Site Number : 8400041
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan Health System - Ann Arbor- Site Number : 8400035
    • Mississippi
      • Flowood, Mississippi, United States, 39232
        • Recruiting
        • Southern Specialty Research- Site Number : 8400059
    • New York
      • Staten Island, New York, United States, 10310
        • Recruiting
        • Richmond University Medical Center- Site Number : 8400038
      • The Bronx, New York, United States, 10467
        • Recruiting
        • Montefiore Medical Center - Moses Campus- Site Number : 8400057
    • South Carolina
      • Greenville, South Carolina, United States, 29605
        • Recruiting
        • Prisma Health- Site Number : 8400051
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • Baylor College of Medicine- Site Number : 8400055
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Recruiting
        • VCU Massey Cancer Center: Dalton Oncology Clinic- Site Number : 8400012

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebo
Pharmaceutical form:Tablet -Route of administration:Oral
Experimental: Rilzabrutinib
Drug: Rilzabrutinib
Pharmaceutical form:Tablet -Route of administration:Oral
Other Names:
  • SAR444671

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
At Week 52

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sanofi

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 12, 2025

Primary Completion (Estimated)

July 23, 2027

Study Completion (Estimated)

December 29, 2028

Study Registration Dates

First Submitted

May 8, 2025

First Submitted That Met QC Criteria

May 8, 2025

First Posted (Actual)

May 16, 2025

Study Record Updates

Last Update Posted (Actual)

July 29, 2026

Last Update Submitted That Met QC Criteria

July 28, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EFC17872
  • 2024-518645-17 (Registry Identifier: CTIS)
  • U1111-1311-1896 (Other Grant/Funding Number: ICTRP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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