The efficacy and safety of rilzabrutinib in participants aged 10 to 65 years with sickle-cell disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

7 Oct 2025 → ongoing

Decision date (initial)

2025-05-23

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2024-518645-17-00

WHO UTN

U1111-1311-1896

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Efficacy, Therapy, Pharmacokinetic, Pharmacogenomic

To assess the efficacy of rilzabrutinib for the prevention of clinical vaso-occlusive crisis (VOC)
(acute painful crisis in sickle-cell disease [SCD] patients).

Secondary objectives 9

1. To evaluate the time to first clinical VOC (vaso-occlusive crisis).
2. To evaluate the rate of visits due to SCD related complications
3. To evaluate the annualized rate of home- managed VOCs.
4. To evaluate the effect of rilzabrutinib on fatigue in adults.
5. To evaluate the effect of rilzabrutinib on hemoglobin (Hb) levels.
6. To evaluate the effect of rilzabrutinib on fatigue in pediatric participants.
7. To evaluate the safety of rilzabrutinib
8. To evaluate the effect of rilzabrutinib on blood transfusion requirement.
9. To evaluate the effect of rilzabrutinib on analgesic usage during the double-blind period

Conditions and MedDRA coding

Blood and lymphatic diseases

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share 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

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Participants who have been diagnosed with SCD.
2. - Participants who have had between ≥2 and ≤10 episodes of documented clinical VOC within 12 months of the screening events.
3. 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.
4. Participants with Eastern Cooperative Oncology Group (ECOG) performance status grade 2 or lower.
5. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
6. 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 8

1. 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
2. Clinically relevant cardiac abnormality, in the opinion of the Investigator or electrocardiogram (ECG) findings.
3. Participants with history of stroke, or history of abnormal transcranial doppler.
4. Participants with uncontrolled or active HBV and/or HCV infection including those receiving antiviral therapy at the time of screening.
5. HIV infection.
6. A history of active or latent tuberculosis (TB)
7. Positive COVID-19 molecular test.
8. Participant is taking or has received crizanlizumab (ADAKVEO®) within 90 days and/or voxelotor (OXBRYTA®) within 30 days prior to the Screening visit.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Annualized rate of clinical VOC

Secondary endpoints 10

1. Time to first clinical VOC incidence
2. Annualized rate of visits due to SCD-related complications as assessed by the Investigator
3. Annualized rate of home-managed VOCs as reported in the Sickle Cell Pain Crisis (SCPC) eDiary
4. Change in fatigue as measured by the PROMIS SF v1.0 Fatigue 13a total score (adults)
5. Change in Hb levels
6. Change in fatigue as measured by the PedsQL Multidimensional Fatigue Scale total score (pediatric participants)
7. Incidence of treatment emergent adverse events (TEAEs), including serious adverse events (SAEs), adverse events of special interest (AESIs) and adverse events leading to discontinuation.
8. Incidence of potentially clinically significant laboratory, vital signs, and ECG abnormalities
9. Absolute number of simple and exchange blood transfusion
10. Number of days requiring acetaminophen, NSAID and/or short-acting opioid usage

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

82 Avenue Raspail

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Global regulatory Affairs

Public contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Global regulatory Affairs

Third parties 11

Locations

7 EU/EEA countries · 27 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 129 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications