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

Sanofi

Status and phase: Enrolling; Phase 3

Conditions: Sickle Cell Disease

Treatments: Drug: Rilzabrutinib; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06975865

U1111-1311-1896 (Other Grant/Funding Number)

2024-518645-17 (Registry Identifier)

EFC17872

Details and patient eligibility

About

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

Enrollment: 192 estimated patients

Sex: All

Ages: 10 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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192 participants in 2 patient groups, including a placebo group

Rilzabrutinib

Experimental group

Description:

Rilzabrutinib

Treatment:

Drug: Rilzabrutinib

Placebo

Placebo Comparator group

Description:

Placebo

Treatment:

Drug: Placebo