Efficacy and Safety of Tocilizumab for Acute Chest Syndrome Treatment in Patients With Sickle Cell Disease
Recruiting
Phase 3Interventional Study
Sickle Cell DiseaseAcute Chest Syndrome
Pivotal Trial
This treatment is in the last trial phase before FDA approval.
Prior Safety Data
This treatment has already been tested in at least one earlier human trial.
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At a Glance
Age
2 and older
Sex
Any
Trial phase
Phase 3
Study type
Interventional
Purpose
Treatment
Participants needed
130 (estimated)
Sponsor
Assistance Publique - Hôpitaux de Paris · Other
Who this trial is looking for
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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).
Trial Locations
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Eligibility Criteria
Inclusion Criteria:
1. SCD patient of all genotypes (SS, SC, S/β0 and S/β+ or other major SCD syndrome)
2. Age ≥ 2 years old
3. 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 ultra…
Inclusion Criteria:
1. SCD patient of all genotypes (SS, SC, S/β0 and S/β+ or other major SCD syndrome)
2. Age ≥ 2 years old
3. 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)
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
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 3 months after the administration of treatment (tocilizumab or placebo)
Exclusion Criteria:
1. Impossibility to perform tocilizumab/placebo injection within the first 48 hours of supplemental oxygen ≥2L/min 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. Current enrolment in another interventional research concerning a medicinal product for human use
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