TOCIACS : Efficacy and safety of Tocilizumab for acute chest syndrome treatment in paediatric and adult patients with sickle cell disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08], Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

27 Aug 2025 → ongoing

Decision date (initial)

2024-10-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

To evaluate the efficacy over placebo of 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) on time to successful weaning from both supplemental oxygen and any respiratory support (non-invasive or invasive), in paediatric and adult Sickle Cell Disease (SCD) patients with Acute Chest Syndrome (ACS).

Secondary objectives 10

1. To evaluate the safety of tocilizumab in SCD patients with ACS by determining the incidence of severe and not severe adverse events during hospitalisation and within 3 months following tocilizumab or placebo injection (including hypertension, hypersensitivity reactions, hypokalaemia, neutropenia, thrombopenia, bacterial infections, pulmonary embolism/thrombosis, hepatic cytolysis, organ failure).
2. To determine tocilizumab level in the plasma and in the sputum (or in the tracheal aspirations in case of invasive mechanical ventilation) 48 (+/- 12) hours after tocilizumab injection.
3. To determine whether tocilizumab reduces length of hospital stay
4. To determine whether tocilizumab reduces mortality (during hospitalisation and within 3 months following tocilizumab or placebo injection)
5. To determine whether tocilizumab reduces need for transfusion and the total number of red blood cell units received during hospitalisation
6. To determine whether tocilizumab reduces need for non-invasive respiratory support (high flow nasal oxygen, continuous positive airway pressure, or bilevel non-invasive ventilation)
7. To determine whether tocilizumab reduces need for invasive ventilatio
8. To determine whether tocilizumab reduces readmission for VOC or ACS within 3 months following tocilizumab or placebo injection
9. To determine whether tocilizumab reduces biological inflammation: C-reactive protein (CRP), procalcitonin (PCT), plasma and sputum IL-6 levels, 48 (+/- 12) hours after tocilizumab or placebo injection
10. To determine whether tocilizumab reduces pulmonary lesions on chest imaging (X-ray or lung ultrasound), 48 (+/- 12) hours after tocilizumab or placebo injection

Conditions and MedDRA coding

Sickle cell disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. SCD patient of all genotypes (SS, SC, S/β0 and S/β+) or other major SCD syndrome
2. Age ≥ 2 years old
3. 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)
4. 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
5. Negative pregnancy test for girls or women of childbearing age (15-50 years old)
6. Freely given, informed and written consent of patient or legal representatives
7. Affiliation to the social security (or health insurance)
8. Effective contraception up to 6 months after treatment administration

Exclusion criteria 16

1. 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.
2. Known hypersensitivity to tocilizumab or its excipients
3. 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)
4. Immunization with a live/attenuated vaccine within the last 4 weeks
5. Immunomodulatory therapy, anti-rejection therapy, cell depleting therapies and investigational agents within the last 3 months
6. History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
7. 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
8. Evidence of malignant disease or malignancies diagnosed within the last 3 years
9. Pregnancy or breastfeeding
10. Imminent and inevitable progression towards death in the opinion of the investigator
11. Absolute neutrophil count < 1.0 G/L or platelets < 50 G/L
12. ALT or AST > 5 fold the upper limit of normal
13. Glomerular Filtration rate (GFR) < 60 mL/min/1,73 m²)
14. History of bowel diverticulitis or gastrointestinal perforation
15. Immunomodulatory or anti-rejection therapy within the last 3 months
16. Current enrolment in another interventional research concerning a medicinal product for human use

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Dr Slimane ALLALI

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Dr Slimane ALLALI

Locations

1 EU/EEA country · 39 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 32 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