Clinical trial • Phase III • Respiratory | Haematology
TOCILIZUMAB for Sickle cell disease
Phase III trial of TOCILIZUMAB for Sickle cell disease.
Overview
- Trial Therapeutic Area
- Respiratory | Haematology
- Trial Disease
- Sickle cell disease
- Trial Stage
- Phase III
- Drug Modality
- Monoclonal antibody | Small molecule
- Paediatric Trial
- Yes
Key dates
- Initial CTIS Submission Date
- 17-06-2024
- First CTIS Authorization Date
- 08-10-2024
Trial design
Randomised, tocilizumab: single intravenous infusion at 8 mg/kg for patients ≥ 30 kg (up to a maximum of 800 mg) and 12 mg/kg for patients < 30 kg; comparator: placebo (chlorure de sodium 0,9 % b. braun, solution injectable en ampoule) administered as an intravenous infusion (single infusion to match active treatment).-controlled Phase III trial in France.
- Randomised
- Yes
- Comparator
- Tocilizumab: single intravenous infusion at 8 mg/kg for patients ≥ 30 kg (up to a maximum of 800 mg) and 12 mg/kg for patients < 30 kg; Comparator: placebo (CHLORURE DE SODIUM 0,9 % B. BRAUN, solution injectable en ampoule) administered as an intravenous infusion (single infusion to match active treatment).
- Target Sample Size
- 130
- Trial Duration For Participant
- 90
Eligibility
Recruits 130 paediatric patients.
- Pregnancy Exclusion
- Pregnancy or breastfeeding
- Vulnerable Population
- Children are included (age ≥ 2 years). The trial requires freely given, informed and written consent of the patient or legal representatives. Age-specific subject information and informed consent forms are provided (documents referencing ages 6-11 and 12-17, parental/guardian authorization forms and assent/consent materials are included), indicating procedures for parental/guardian authorization and minor assent.
Inclusion criteria
- {"criterion_text":"- SCD patient of all genotypes (SS, SC, S/β0 and S/β+) or other major SCD syndrome\n- Age ≥ 2 years old\n- Hospitalised for ACS, defined by the WHO as the association of fever and/or acute respiratory symptoms with a new pulmonary infiltrate on chest imaging, (X-ray, lung ultrasound, or CT scan)\n- Requiring supplemental oxygen ≥ 2 L/min for SpO2 ≥ 95% or non-invasive respiratory support (high flow nasal oxygen or continuous positive airway pressure or bilevel non-invasive ventilation) or invasive mechanical ventilation or ECMO, for less than 48 hours\n- Negative pregnancy test for girls or women of childbearing age (15-50 years old)\n- Freely given, informed and written consent of patient or legal representatives\n- Affiliation to the social security (or health insurance)\n- Effective contraception up to 6 months after treatment administration"}
Exclusion criteria
- {"criterion_text":"- Impossibility to perform tocilizumab/placebo injection within the first 48 hours of supplemental oxygen ≥2L/min or for SpO2≥95% and/or respiratory support (as defined in inclusion criteria n°4). If exchange transfusion is indicated at inclusion, it has to be performed before the injection of tocilizumab/placebo.\n- Imminent and inevitable progression towards death in the opinion of the investigator\n- Absolute neutrophil count < 1.0 G/L or platelets < 50 G/L\n- ALT or AST > 5 fold the upper limit of normal\n- Glomerular Filtration rate (GFR) < 60 mL/min/1,73 m²)\n- History of bowel diverticulitis or gastrointestinal perforation\n- Immunomodulatory or anti-rejection therapy within the last 3 months\n- Current enrolment in another interventional research concerning a medicinal product for human use\n- Known hypersensitivity to tocilizumab or its excipients\n- Known active current severe bacterial, viral, fungal, mycobacterial, or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, hepatitis B and C, and herpes zoster)\n- Immunization with a live/attenuated vaccine within the last 4 weeks\n- Immunomodulatory therapy, anti-rejection therapy, cell depleting therapies and investigational agents within the last 3 months\n- History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies\n- History of diverticulitis, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower gastrointestinal disease such as Crohn's disease, ulcerative colitis, or other symptomatic lower gastrointestinal conditions that might predispose a patient to perforations\n- Evidence of malignant disease or malignancies diagnosed within the last 3 years\n- Pregnancy or breastfeeding"}
Endpoints
Primary endpoints
- {"endpoint_text":"- Time to successful weaning from both supplemental oxygen and any respiratory support, defined as SpO2 ≥ 95% without oxygen during the next 24 hours, and spontaneous breathing without any respiratory support (non-invasive or invasive) during the next 48 hours.","definition_or_measurement_approach":"Time-to-event endpoint: time from randomisation/investigational injection to achievement of the defined weaning criteria (SpO2 ≥ 95% without oxygen for 24 hours and spontaneous breathing without respiratory support for 48 hours)."}
Recruitment
- Planned Sample Size
- 130
- Recruitment Window Months
- 27
- Consent Approach
- Informed and written consent required from the patient or legal representatives. Age-specific subject information and consent/assent forms are provided (including forms for ages 6-11 and 12-17, parental/guardian authorization forms, adult ICF and proxy forms). The documentation set includes multiple subject information and informed consent form versions and parental authorization forms indicating procedures for assent and parental consent.
Geography
- Total Number Of Sites
- 38
- Total Number Of Participants
- 130
France
- Earliest CTIS Part Ii Submission Date
- 29-08-2024
- Latest Decision Or Authorization Date
- 13-03-2026
- Processing Time Days
- 561
- Number Of Sites
- 38
- Number Of Participants
- 130
Sites
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Internal Medicine
- Principal Investigator Name
- Aline SANTIN
- Principal Investigator Email
- aline.santin@aphp.fr
- Contact Person Name
- Aline SANTIN
- Contact Person Email
- aline.santin@aphp.fr
- Site Name
- Centre Hospitalier Universitaire Rouen
- Department Name
- Paediatric intensive care
- Principal Investigator Name
- Aurélie LABARRE
- Principal Investigator Email
- aurelie.labarre@chu-rouen.fr
- Contact Person Name
- Aurélie LABARRE
- Contact Person Email
- aurelie.labarre@chu-rouen.fr
- Site Name
- Centre Hospitalier Universitaire De Toulouse
- Department Name
- Internal Medicine
- Principal Investigator Name
- Pierre COUGOUL
- Principal Investigator Email
- cougoul.pierre@iuct-oncopole.fr
- Contact Person Name
- Pierre COUGOUL
- Contact Person Email
- cougoul.pierre@iuct-oncopole.fr
- Site Name
- Centre Hospitalier Universitaire Rouen
- Department Name
- Paediatric Haematology
- Principal Investigator Name
- Cécile DUMESNIL
- Principal Investigator Email
- cecile.dumesnil@chu-rouen.fr
- Contact Person Name
- Cécile DUMESNIL
- Contact Person Email
- cecile.dumesnil@chu-rouen.fr
- Site Name
- Centre Hospitalier Universitaire Rouen
- Department Name
- Intensive care
- Principal Investigator Name
- Maximilien GRALL
- Principal Investigator Email
- maximilien.grall@chu-rouen.fr
- Contact Person Name
- Maximilien GRALL
- Contact Person Email
- maximilien.grall@chu-rouen.fr
- Site Name
- Centre Hospitalier Intercommunal Creteil
- Department Name
- Intensive care
- Principal Investigator Name
- Francesca SANTI
- Principal Investigator Email
- francesca.santi@chicreteil.fr
- Contact Person Name
- Francesca SANTI
- Contact Person Email
- francesca.santi@chicreteil.fr
- Site Name
- Centre Hospitalier Universitaire Rouen
- Department Name
- Internal Medicine
- Principal Investigator Name
- Maximilien GRALL
- Principal Investigator Email
- maximilien.grall@chu-rouen.fr
- Contact Person Name
- Maximilien GRALL
- Contact Person Email
- maximilien.grall@chu-rouen.fr
- Site Name
- Centre Hospitalier Intercommunal Creteil
- Department Name
- Internal Medicine
- Principal Investigator Name
- Isabelle GENTY
- Principal Investigator Email
- isabelle.genty@chicreteil.fr
- Contact Person Name
- Isabelle GENTY
- Contact Person Email
- isabelle.genty@chicreteil.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Intensive care
- Principal Investigator Name
- Armand MEKONTSO DESSAP
- Principal Investigator Email
- armand.dessap@aphp.fr
- Contact Person Name
- Armand MEKONTSO DESSAP
- Contact Person Email
- armand.dessap@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Internal Medicine
- Principal Investigator Name
- Jean-Benoit ARLET
- Principal Investigator Email
- jean-benoit.arlet@aphp.fr
- Contact Person Name
- Jean-Benoit ARLET
- Contact Person Email
- jean-benoit.arlet@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Paediatric intensive care
- Principal Investigator Name
- Jordi MIATELLO
- Principal Investigator Email
- jordi.matiello@aphp.fr
- Contact Person Name
- Jordi MIATELLO
- Contact Person Email
- jordi.matiello@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Intensive care
- Principal Investigator Name
- Damien ROUX
- Principal Investigator Email
- damien.roux@aphp.fr
- Contact Person Name
- Damien ROUX
- Contact Person Email
- damien.roux@aphp.fr
- Site Name
- Centre Hospitalier Universitaire De Toulouse
- Department Name
- Paediatric intensive care
- Principal Investigator Name
- Sonia PELLUAU
- Principal Investigator Email
- pelluau.s@chu-toulouse.fr
- Contact Person Name
- Sonia PELLUAU
- Contact Person Email
- pelluau.s@chu-toulouse.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Downstream Emergency department
- Principal Investigator Name
- Henri GUILLET
- Principal Investigator Email
- henri.guillet@aphp.fr
- Contact Person Name
- Henri GUILLET
- Contact Person Email
- henri.guillet@aphp.fr
- Site Name
- Hospices Civils De Lyon
- Department Name
- Internal Medicine
- Principal Investigator Name
- Giovanna CANNAS
- Principal Investigator Email
- giovanna.cannas@chu-lyon.fr
- Contact Person Name
- Giovanna CANNAS
- Contact Person Email
- giovanna.cannas@chu-lyon.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Intensive care
- Principal Investigator Name
- Laurent GUERIN
- Principal Investigator Email
- laurent.geurin@aphp.fr
- Contact Person Name
- Laurent GUERIN
- Contact Person Email
- laurent.geurin@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Internal Medicine
- Principal Investigator Name
- Stéphanie GUILLET
- Principal Investigator Email
- stephanie.guillet@aphp.fr
- Contact Person Name
- Stéphanie GUILLET
- Contact Person Email
- stephanie.guillet@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Genetic Red Blood Cell Disease/ Internal Medicine
- Principal Investigator Name
- Anoosha HABIBI
- Principal Investigator Email
- anoosha.habibi@aphp.fr
- Contact Person Name
- Anoosha HABIBI
- Contact Person Email
- anoosha.habibi@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Internal Medicine
- Principal Investigator Name
- Christelle CHANTALAT AUGER
- Principal Investigator Email
- christelle.chantalat@aphp.fr
- Contact Person Name
- Christelle CHANTALAT AUGER
- Contact Person Email
- christelle.chantalat@aphp.fr
- Site Name
- Centre Hospitalier Universitaire De Toulouse
- Department Name
- Paediatric Haematology
- Principal Investigator Name
- Marie-Pierre CASTEX
- Principal Investigator Email
- castex.mp@chu-toulouse.fr
- Contact Person Name
- Marie-Pierre CASTEX
- Contact Person Email
- castex.mp@chu-toulouse.fr
- Site Name
- Centre Hospitalier Regional De Marseille
- Department Name
- Internal Medicine
- Principal Investigator Name
- Estelle JEAN-MIGNARD
- Principal Investigator Email
- estelle.jean@ap-hm.fr
- Contact Person Name
- Estelle JEAN-MIGNARD
- Contact Person Email
- estelle.jean@ap-hm.fr
- Site Name
- Centre Hospitalier Intercommunal Creteil
- Department Name
- Paediatrics
- Principal Investigator Name
- Céline DELESTRAIN
- Principal Investigator Email
- celine.delestrain@chicreteil.fr
- Contact Person Name
- Céline DELESTRAIN
- Contact Person Email
- celine.delestrain@chicreteil.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Paediatrics
- Principal Investigator Name
- Corinne GUITTON
- Principal Investigator Email
- corinne.guitton@aphp.fr
- Contact Person Name
- Corinne GUITTON
- Contact Person Email
- corinne.guitton@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Infectious and tropical disease/Clinical Immunology
- Principal Investigator Name
- William VINDRIOS
- Principal Investigator Email
- william.vindrios@aphp.fr
- Contact Person Name
- William VINDRIOS
- Contact Person Email
- william.vindrios@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Paediatric intensive care
- Principal Investigator Name
- Pierre-Louis LEGER
- Principal Investigator Email
- pierre-louis.leger@aphp.fr
- Contact Person Name
- Pierre-Louis LEGER
- Contact Person Email
- pierre-louis.leger@aphp.fr
- Site Name
- Centre Hospitalier Universitaire De Toulouse
- Department Name
- Intensive care
- Principal Investigator Name
- Jean RUIZ
- Principal Investigator Email
- ruiz.jean@chu-toulouse.fr
- Contact Person Name
- Jean RUIZ
- Contact Person Email
- ruiz.jean@chu-toulouse.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Paediatrics
- Principal Investigator Name
- Bérengère KOEHL
- Principal Investigator Email
- berengere.koehl@aphp.fr
- Contact Person Name
- Bérengère KOEHL
- Contact Person Email
- berengere.koehl@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Internal Medicine
- Principal Investigator Name
- Louis AFFO
- Principal Investigator Email
- louis.affo@aphp.fr
- Contact Person Name
- Louis AFFO
- Contact Person Email
- louis.affo@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Intensive care
- Principal Investigator Name
- Johanna OZIEL
- Principal Investigator Email
- johanna.oziel@aphp.fr
- Contact Person Name
- Johanna OZIEL
- Contact Person Email
- johanna.oziel@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Intensive care
- Principal Investigator Name
- Jean-Benoit ARLET
- Principal Investigator Email
- jean-benoit.arlet@aphp.fr
- Contact Person Name
- Jean-Benoit ARLET
- Contact Person Email
- jean-benoit.arlet@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Paediatric intensive care
- Principal Investigator Name
- Claire HEILBRONNER
- Principal Investigator Email
- claire.heilbronner@aphp.fr
- Contact Person Name
- Claire HEILBRONNER
- Contact Person Email
- claire.heilbronner@aphp.fr
- Site Name
- Hospices Civils De Lyon
- Department Name
- Intensive care
- Principal Investigator Name
- Marion CALMETTES
- Principal Investigator Email
- marion.calmettes@chu-lyon.fr
- Contact Person Name
- Marion CALMETTES
- Contact Person Email
- marion.calmettes@chu-lyon.fr
Sponsor
Primary sponsor
- Full Name
- Assistance Publique Hopitaux De Paris
- Organisation Type
- Hospital/Clinic/Other health care facility
- Country Of Registered Address
- France
Investigational products
- Investigational Product Name
- TOCILIZUMAB
- Active Substance
- TOCILIZUMAB
- Modality
- Monoclonal antibody
- Routes Of Administration
- Intravenous infusion
- Route
- Intravenous infusion
- Starting Dose
- 8 mg/kg (patients ≥ 30 kg, up to a maximum of 800 mg) and 12 mg/kg (patients < 30 kg)
- Dose Levels
- Single-dose weight-based: 8 mg/kg (≥30 kg) / 12 mg/kg (<30 kg)
- Frequency
- Single infusion
- Maximum Dose
- 800 mg
- Investigational Product Name
- CHLORURE DE SODIUM 0,9 % B. BRAUN, solution injectable en ampoule
- Active Substance
- SODIUM CHLORIDE
- Modality
- Small molecule
- Routes Of Administration
- Intravenous infusion
- Route
- Intravenous infusion
- Authorisation Status
- Marketing authorisation number: 34009 560 232 4 0
- Frequency
- Single infusion (placebo)
- Maximum Dose
- 20 ml
Related trials
Other published trials that may interest you.