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

Official title

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

Overview

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

• Drug Rilzabrutinib
  Pharmaceutical form:Tablet -Route of administration:Oral
• Drug Placebo
  Pharmaceutical form:Tablet -Route of administration:Oral

Primary outcome measures

• Annualized rate of clinical VOC [Time frame: At Week 52]

Secondary outcome measures (10)

• Time to first clinical VOC incidence [Time frame: Until Week 52]
• Annualized rate of visits due to SCD-related complications as assessed by the Investigator [Time frame: At Week 52]
• Annualized rate of home-managed VOCs as reported in the Sickle Cell Pain Crisis (SCPC) eDiary [Time frame: 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]
• Change in Hb levels [Time frame: 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]
• 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]
• Incidence of potentially clinically significant laboratory, vital signs, and ECG abnormalities [Time frame: Until Week 52]
• Absolute number of simple and exchange blood transfusion [Time frame: Until Week 52]
• Number of days requiring acetaminophen, NSAID and/or short-acting opioid usage [Time frame: Until Week 52]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 16 centers

• University of Alabama at Birmingham- Site Number : 8400003 — Birmingham
• Phoenix Children's Hospital- Site Number : 8400028 — Phoenix
• University of California San Francisco- Site Number : 8400040 — Fresno
• Oncology & Hematology Associates of West Broward- Site Number : 8400029 — Coral Springs
• Sylvester Comprehensive Cancer Center- Site Number : 8400020 — Miami
• University of Illinois-Chicago - College of Medicine- Site Number : 8400054 — Chicago
• Indiana University Health Riley Hospital for Children- Site Number : 8400056 — Indianapolis
• Louisiana State University Health Sciences Center - Shreveport- Site Number : 8400037 — Shreveport
• … and 8 more centers

Italy · 7 centers

• Azienda Ospedaliero Universitaria Careggi SOD Ematologia-Site Number : 3800006 — Florence
• Investigational Site Number : 3800004 — Milan
• Azienda Ospedaliera Universitaria, Università della Campania "Luigi Vanvitelli" Napoli-Sit — Naples
• IRCCS Ospedale Pediatrico Bambino Gesù-Site Number : 3800001 — Rome
• Azienda Ospedaliera Universitaria San Luigi Gonzaga, SSD Microcitemie Malattie Rare Ematol — Orbassano
• Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello-Site Number : 3800002 — Palermo
• Centro Ricerche Cliniche Verona s.r.l. presso Ospedale G.B. Rossi Borgo Roma-Site Number : — Verona

Brazil · 5 centers

• Hospital Santa Izabel- Site Number : 0760006 — Salvador
• Universidade Federal de Goias- Site Number : 0760002 — Goiânia
• Fundação Faculdade Regional de Medicina de São José do Rio Preto- Site Number : 0760001 — São José do Rio Preto
• Pontifícia Universidade Católica do Rio de Janeiro- Site Number : 0760009 — Rio de Janeiro
• Hospital Samaritano De Sao Paulo- Site Number : 0760005 — São Paulo

France · 4 centers

• Investigational Site Number : 2500002 — Créteil
• Investigational Site Number : 2500005 — Marseille
• Investigational Site Number : 2500001 — Paris
• Investigational Site Number : 2500004 — Toulouse

Israel · 4 centers

• Investigational Site Number : 3760001 — Afula
• Investigational Site Number : 3760002 — Afula
• Investigational Site Number : 3760005 — Haifa
• Investigational Site Number : 3760006 — Haifa

Belgium · 3 centers

• Investigational Site Number : 0560003 — Brussels
• Investigational Site Number : 0560002 — Brussels
• Investigational Site Number : 0560001 — Leuven

Greece · 3 centers

• Investigational Site Number : 3000001 — Athens
• Investigational Site Number : 3000003 — Athens
• Investigational Site Number : 3000002 — Pátrai

Turkey (Türkiye) · 3 centers

• Investigational Site Number : 7920001 — Adana
• Investigational Site Number : 7920002 — Adana
• Investigational Site Number : 7920003 — Mersin

Germany · 2 centers

• Investigational Site Number : 2760002 — Essen
• Investigational Site Number : 2760004 — Stuttgart

Spain · 2 centers

• Investigational Site Number : 7240002 — Madrid
• Investigational Site Number : 7240001 — Madrid

United Kingdom · 2 centers

• Investigational Site Number : 8260002 — London
• Investigational Site Number : 8260001 — London

Netherlands · 1 center

• Investigational Site Number : 5280002 — Rotterdam

Oman · 1 center

• Investigational Site Number : 5120001 — Muscat

Identifiers

NCT: NCT06975865 · EFC17872 · 2024-518645-17 · U1111-1311-1896

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗