Clinical trial • Phase III • Haematology

RILZABRUTINIB for Sickle cell disease

Phase III trial of RILZABRUTINIB for Sickle cell disease.

Overview

Trial Therapeutic Area
Haematology
Trial Disease
Sickle cell disease
Trial Stage
Phase III
Drug Modality
Small molecule
Paediatric Trial
Yes
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
24-01-2025
First CTIS Authorization Date
20-05-2025

Trial design

Randomised, sar444671 placebo - matched placebo for test (placebo comparator); dose and schedule not specified in provided record-controlled, adaptive Phase III trial in Belgium, Netherlands, Germany and others.

Randomised
Yes
Comparator
Sar444671 placebo - matched placebo for test (placebo comparator); dose and schedule not specified in provided record
Adaptive
True, group sequential design (group sequential, implying planned interim analyses/group sequential stopping boundaries)
Target Sample Size
135
Trial Duration For Participant
364

Eligibility

Recruits 135 paediatric patients.

Vulnerable Population
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. Assent from minors is not explicitly described in the provided criteria.

Inclusion criteria

  • {"criterion_text":"- Participants who have been diagnosed with SCD.\n- Participants who have had between ≥2 to ≤10 episodes of documented acute clinical VOC within 12 months of the screening visit.\n- 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.\n- Participants with Eastern Cooperative Oncology Group (ECOG) performance status grade 2 or lower.\n- Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.\n- 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

  • {"criterion_text":"- 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\n- Clinically relevant cardiac abnormality, in the opinion of the Investigator or electrocardiogram (ECG) findings.\n- Participants with history of stroke, or history of abnormal transcranial doppler.\n- Participants with uncontrolled or active HBV and/or HCV infection including those receiving antiviral therapy at the time of screening.\n- HIV infection.\n- A history of active or latent tuberculosis (TB)\n- Positive COVID-19 molecular test.\n- 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 endpoints

  • {"endpoint_text":"- Annualized rate of clinical VOC","definition_or_measurement_approach":""}

Secondary endpoints

  • {"endpoint_text":"- Time to first clinical VOC incidence","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Annualized rate of visits due to SCD-related complications as assessed by the Investigator","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Annualized rate of home-managed VOCs as reported in the Sickle Cell Pain Crisis (SCPC) eDiary","definition_or_measurement_approach":"As reported in the Sickle Cell Pain Crisis (SCPC) eDiary"}
  • {"endpoint_text":"- Change in fatigue as measured by the PROMIS SF v1.0 Fatigue 13a total score (adults)","definition_or_measurement_approach":"Measured by the PROMIS SF v1.0 Fatigue 13a total score (adults)"}
  • {"endpoint_text":"- Change in Hb levels","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Change in fatigue as measured by the PedsQL Multidimensional Fatigue Scale total score (pediatric participants)","definition_or_measurement_approach":"Measured by the PedsQL Multidimensional Fatigue Scale total score (pediatric participants)"}
  • {"endpoint_text":"- Incidence of treatment emergent adverse events (TEAEs), including serious adverse events (SAEs), adverse events of special interest (AESIs) and adverse events leading to discontinuation.","definition_or_measurement_approach":"Includes TEAEs, SAEs, AESIs and AEs leading to discontinuation as reported during treatment"}
  • {"endpoint_text":"- Incidence of potentially clinically significant laboratory, vital signs, and ECG abnormalities","definition_or_measurement_approach":"Potentially clinically significant abnormalities in laboratory tests, vital signs, and ECG"}
  • {"endpoint_text":"- Absolute number of simple and exchange blood transfusion","definition_or_measurement_approach":"Count of simple and exchange blood transfusions"}
  • {"endpoint_text":"- Number of days requiring acetaminophen, NSAID and/or short-acting opioid usage","definition_or_measurement_approach":"Number of days with acetaminophen, NSAID and/or short-acting opioid use"}

Recruitment

Registry Or Advocacy Recruitment
True, Patient advocacy groups (not specified by name)
Digital Remote Recruitment
True, includes banner ads, patient-advocacy-group emails, medical-trigger-email and other digital recruitment materials (e.g., online advertisements); eDiary (SCPC) used for outcome reporting
Planned Sample Size
135
Recruitment Window Months
38
Consent Approach
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." Subject information and informed consent form documents are available in multiple languages (English, Dutch, French, Greek, German, Italian, Spanish). Assent procedures for minors are not explicitly described in the provided materials.

Methods

  • HCP referral letters (country-specific HCP referral letters listed in recruitment materials)
  • Patient-advocacy-group emails (patient-advocacy-group-email files present)
  • Posters (country/language-specific recruitment posters)
  • Banner advertisements (online banner ads)
  • K1 recruitment arrangements (general recruitment arrangements documents in English and other languages)
  • Medical-trigger emails (country-specific medical-trigger-email listed for Italy)
  • Advertisement banners (country-specific advertisement/banner materials)

Geography

Total Number Of Sites
25
Total Number Of Participants
58

Belgium

Earliest CTIS Part Ii Submission Date
17-04-2025
Latest Decision Or Authorization Date
23-05-2025
Processing Time Days
36
Number Of Sites
3
Number Of Participants
9

Sites

Site Name
UZ Leuven
Department Name
UZ Leuven - Gasthuisberg Campus
Contact Person Name
Timothy Devos
Contact Person Email
timothy.devos@uzleuven.be
Site Name
Association Hospitaliere De Bruxelles Et De Schaerbeek Centre Hospitalier Universitaire Brugmann
Department Name
Centre Hospitalier Universitaire Brugmann
Contact Person Name
Marie-Agnes Azerad
Contact Person Email
inv.1870719.25@dd-proxy.com
Site Name
Hopital Erasme
Department Name
HUB Erasme
Contact Person Name
Martin Colard
Contact Person Email
martin.colard@hubruxelles.be

Netherlands

Earliest CTIS Part Ii Submission Date
15-04-2025
Latest Decision Or Authorization Date
26-05-2025
Processing Time Days
41
Number Of Sites
1
Number Of Participants
6

Sites

Site Name
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Department Name
Afdeling Hematologie
Contact Person Name
Anita Rijneveld
Contact Person Email
a.rijneveld@erasmusmc.nl

Germany

Earliest CTIS Part Ii Submission Date
22-04-2025
Latest Decision Or Authorization Date
11-08-2025
Processing Time Days
111
Number Of Sites
3
Number Of Participants
10

Sites

Site Name
University Hospital Cologne AöR
Department Name
Universitätsklinikum Köln
Contact Person Name
Janine Boell
Contact Person Email
janine.boell@uk-koeln.de
Site Name
Universitaetsklinikum Essen AöR
Department Name
Hämatologie/Stammzellentransplantation
Contact Person Name
Ferras Alashkar
Contact Person Email
ferras.alashkar@uk-essen.de
Site Name
Robert Bosch Gesellschaft fuer medizinische Forschung mbH
Department Name
Robert Bosch Gesellschaft für Medizinische Forschung mbH
Contact Person Name
Anette Hoferer
Contact Person Email
anette.hoferer@rbk.de

France

Earliest CTIS Part Ii Submission Date
11-04-2025
Latest Decision Or Authorization Date
26-05-2025
Processing Time Days
45
Number Of Sites
4
Number Of Participants
9

Sites

Site Name
Hôpital Henri Mondor
Department Name
Unité des Maladies Génétiques du Globule Rouge (UMGGR) – Centre de Drépanocytose
Contact Person Name
Gonzalo De Luna
Contact Person Email
gonzalo.deluna@aphp.fr
Site Name
Oncopole Claudius Regaud
Department Name
Service de Médecine Interne
Contact Person Name
Pierre Cougoul
Site Name
Centre Hospitalier Regional De Marseille
Department Name
Centre de Référence des Syndromes Drépanocytaires Majeurs
Contact Person Name
Estelle Jean-Mignard
Contact Person Email
estelle.jean@ap-hm.fr
Site Name
Hopital Necker Enfants Malades
Department Name
Hopital Necker Enfants Malades
Contact Person Name
Laure Joseph
Contact Person Email
laure.joseph@aphp.fr

Greece

Earliest CTIS Part Ii Submission Date
06-02-2025
Latest Decision Or Authorization Date
20-05-2025
Processing Time Days
103
Number Of Sites
3
Number Of Participants
6

Sites

Site Name
Nosokomeio Paidon I Agia Sofia
Department Name
1st Department of Pediatrics
Contact Person Name
Antonis Kattamis
Contact Person Email
ankatt@med.uoa.gr
Site Name
Laiko General Hospital Of Athens
Department Name
Center of Expertise in Rare Hematological Diseases
Contact Person Name
Maria Dimopoulou
Contact Person Email
mdimkma@gmail.com
Site Name
General University Hospital Of Patras
Department Name
Department of Hematology
Contact Person Name
Alexandros Spyridonidis
Contact Person Email
aspyridonidis183@gmail.com

Italy

Earliest CTIS Part Ii Submission Date
17-04-2025
Latest Decision Or Authorization Date
21-05-2025
Processing Time Days
34
Number Of Sites
8
Number Of Participants
11

Sites

Site Name
Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
Department Name
U.O.C. Ematologia per le Malattie Rare del Sangue e degli Organi Ematopoietici
Contact Person Name
Rosario Di Maggio
Contact Person Email
rdm83@hotmail.it
Site Name
Azienda Ospedaliero Universitaria Careggi
Department Name
DH Ematologia - PAD 16 San Luca Vecchio
Contact Person Name
Valentina Carrai
Contact Person Email
carraiv@aou-careggi.toscana.it
Site Name
Centro Ricerche Cliniche Di Verona S.r.l.
Department Name
UOC Medicina Generale B AOUI Verona
Contact Person Name
Lucia De Franceschi
Contact Person Email
lucia.defranceschi@univr.it
Site Name
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Department Name
SS Emoglobinopatie, disordini ereditari del metabolismo e del sistema immunitario
Contact Person Name
Giovanna Graziadei
Site Name
Azienda Ospedaliero-Universitaria San Luigi Gonzaga
Department Name
S.C.D.U.Microcitemie e malattie rare ematologiche
Contact Person Name
Vincenzo Voi
Contact Person Email
vincenzo.voi@unito.it
Site Name
Ospedale Pediatrico Bambino Gesu
Department Name
Oncohaematology and Cell Therapy Clinical Trials Area
Contact Person Name
Franco Locatelli
Contact Person Email
franco.locatelli@opbg.net
Site Name
Ente Ospedaliero Ospedali Galliera Di Genova
Department Name
S.S.D. Microcitemia e delle Anemie Congenite
Contact Person Name
Manuela Balocco
Contact Person Email
manuela.balocco@galliera.it
Site Name
Azienda Ospedaliera Universita' Degli Studi Della Campania Luigi Vanvitelli
Department Name
Dipartimento della donna, del bambino e di chirugia generale e specialistica
Contact Person Name
Silverio Perrotta

Spain

Earliest CTIS Part Ii Submission Date
16-04-2025
Latest Decision Or Authorization Date
20-05-2025
Processing Time Days
34
Number Of Sites
3
Number Of Participants
7

Sites

Site Name
Hospital General Universitario Gregorio Maranon
Department Name
Unidad Hemato-oncológica pediátrica y del adolescente
Contact Person Name
Elena Cela de Julian
Contact Person Email
elena.cela@salud.madrid.org
Site Name
Hospital Sant Joan De Deu Barcelona
Department Name
Servicio de Hematología Pediátrica
Contact Person Name
Anna Ruiz Llobet
Site Name
Hospital Universitario La Paz
Department Name
Hematology
Contact Person Name
Ana Martinez Mendoza
Contact Person Email
anamendoz94@gmail.com

Sponsor

Primary sponsor

Full Name
Sanofi-Aventis Recherche & Developpement
Organisation Type
Pharmaceutical company
Country Of Registered Address
France

Contract research organisations

Name
Clinigma ApS
Responsibilities
sponsorDuties codes: [15]; In-trial interviews
Name
Fisher Clinical Services UK Limited
Responsibilities
sponsorDuties codes: [14]
Name
Suvoda LLC
Responsibilities
sponsorDuties codes: [3]
Name
Eresearchtechnology Inc.
Responsibilities
sponsorDuties codes: [7]
Name
MARKEN Germany GmbH
Responsibilities
sponsorDuties codes: [14] (logistics)
Name
Labcorp Central Laboratory Services SARL
Responsibilities
sponsorDuties codes: [4] (central laboratory services)
Name
Azenta US Inc.
Responsibilities
sponsorDuties codes: [4] (sample services / lab vendor)
Name
ESMS Global Limited
Responsibilities
sponsorDuties codes: [15]; Centralized 24-Hour Emergency System

Third parties

  • {"country":"Greece","full_name":"Bioiatriki Private Medical Polyclinic S.A.","duties_or_roles":"sponsorDuties codes: [4]; contact: apapadaki@bioiatriki.gr","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"Germany","full_name":"MARKEN Germany GmbH","duties_or_roles":"sponsorDuties codes: [14]; contact: Francine.duc@marken.com","organisation_type":"Pharmaceutical company (logistics/vendor)"}
  • {"country":"Denmark","full_name":"Clinigma ApS","duties_or_roles":"sponsorDuties codes: [15]; value: \"In-trial interviews\"; contact: JHK@clinigma.com","organisation_type":"Pharmaceutical company / Clinical vendor"}
  • {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"sponsorDuties codes: [4]; contact: isabelle.sagardoy@labcorp.com","organisation_type":"Pharmaceutical company / Central laboratory"}
  • {"country":"United Kingdom","full_name":"Fisher Clinical Services UK Limited","duties_or_roles":"sponsorDuties codes: [14]; contact: rita.fitzpatrick@esmsglobal.com","organisation_type":"Pharmaceutical company / Vendor"}
  • {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"sponsorDuties codes: [3]; contact: qualityassurance@suvoda.com","organisation_type":"Non-Pharmaceutical company / eClinical vendor"}
  • {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"sponsorDuties codes: [4]; contact: Michael.Haussmann@azenta.com","organisation_type":"Pharmaceutical company / Laboratory services"}
  • {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"sponsorDuties codes: [7]; contact: customercare@ert.com","organisation_type":"Pharmaceutical company / Vendor (ERT)"}
  • {"country":"United Kingdom","full_name":"ESMS Global Limited","duties_or_roles":"sponsorDuties codes: [15]; value: \"Centralized 24-Hour Emergency System\"; contact: rita.fitzpatrick@esmsglobal.com","organisation_type":"Pharmaceutical company / Vendor"}

Investigational products

Investigational Product Name
Rilzabrutinib
Active Substance
RILZABRUTINIB
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Authorised (prodAuthStatus:1 present in product dictionary)
Orphan Designation
Yes
Maximum Dose
800 mg (max daily dose amount 800 mg)
Investigational Product Name
Sar444671 placebo - matched placebo for test
Modality
Other

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