Efficacy and Safety of Tocilizumab for Acute Chest Syndrome Treatment in Patients With Sickle Cell Disease

NCT06818266 | Not Yet Recruiting Phase 3 DMC

• 2 other identifiers: APHP2207972023-505109-17-00
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether a single infusion of tocilizumab is effective in reducing the time to successful weaning from both supplemental oxygen and any respiratory support, in pediatric and adult patients with sickle cell disease (SCD) during acute chest syndrome (ACS).

Conditions

Sickle Cell Disease; Acute Chest Syndrome

Keywords

Sickle cell disease; Acute chest syndrome; Tocilizumab

Outcome Measures

Primary Outcomes (1)

• Time to successful weaning from both supplemental oxygen and any respiratory support

  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

  During hospitalization for ACS, from randomization until day 28 after randomization

Secondary Outcomes (15)

• Adverse events during hospitalization and within 3 months following tocilizumab or placebo injection

  Within 3 months after randomization

• Time to discharge

  From the date of randomization until the date of end of hospitalization, assessed up to 3 months

• Mortality

  Within 3 months after randomization

• Need for transfusion

  From the date of randomization until the date of end of hospitalization, assessed up to 3 months

• Total number of red blood cell units received

  From the date of randomization until the date of end of hospitalization, assessed up to 3 months

Study Arms (2)

Arms A : Tocilizumab (RoActemra®, 20 mg/mL)

EXPERIMENTAL

One single intravenous infusion at 8 mg/kg (up to a maximum of 800 mg) for patients ≥ 30 kg and 12 mg/kg for patients \< 30 kg.

Drug: Tocilizumab (RoActemra®, 20 mg/mL).

Arm B : Placebo (NaCl 0.9%)

PLACEBO COMPARATOR

One single intravenous infusion

Drug: Placebo (NaCl 0.9%)

Interventions

Tocilizumab (RoActemra®, 20 mg/mL). DRUG

One single intravenous infusion at 8 mg/kg (up to a maximum of 800 mg) for patients ≥ 30 kg and 12 mg/kg for patients \< 30 kg

Arms A : Tocilizumab (RoActemra®, 20 mg/mL)

Placebo (NaCl 0.9%) DRUG

One single intravenous infusion

Arm B : Placebo (NaCl 0.9%)

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• SCD patient of all genotypes (SS, SC, S/β0 and S/β+)
• Age ≥ 2 years old
• Hospitalized 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)
• 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
• Negative pregnancy test for girls or women of childbearing age
• Freely given, informed and written consent of patient or legal representatives
• Affiliation to the social security (or health insurance)
• Effective contraception up to 3 months after the administration of treatment (tocilizumab or placebo)

You may not qualify if:

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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Department of General Pediatrics and Sickle Cell Center, Necker-Enfants malades Hospital

Paris, 75015, France

Location

MeSH Terms

Conditions

Anemia, Sickle Cell; Acute Chest Syndrome

Interventions

tocilizumab; Sodium Chloride

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Slimane ALLALI, MD, PhD

  Department of General Pediatrics and Sickle Cell Center, Necker-Enfants malades Hospital, Paris, France

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Slimane ALLALI, MD, PhD

CONTACT

01 44 49 48 96; slimane.allali@aphp.fr

Aminata TRAORE, Project advisor

CONTACT

aminata.traore@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2025
• First Posted: February 10, 2025
• Study Start: April 1, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: March 11, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)