Evaluation of Tocilizumab Efficacy and Safety in Treating Acute Chest Syndrome in Pediatric and Adult Sickle Cell Disease Patients

The primary objective of this study is to evaluate the **efficacy** of tocilizumab compared to placebo in reducing the time to successful weaning from both supplemental oxygen and any respiratory support, whether non-invasive or invasive, in pediatric and adult patients with **Sickle Cell Disease** (SCD) experiencing **Acute Chest Syndrome** (ACS). This is clinically relevant as ACS is a severe complication of SCD, and effective management can significantly improve patient outcomes and reduce morbidity.

Secondary objectives include:

• Evaluating the safety of tocilizumab in SCD patients with ACS by determining the incidence of severe and non-severe adverse events during hospitalization and within 3 months following tocilizumab or placebo injection.
• Determining tocilizumab levels in plasma and sputum (or tracheal aspirations in case of invasive mechanical ventilation) 48 hours after injection.
• Assessing whether tocilizumab reduces the length of hospital stay, mortality, need for transfusion, and the total number of red blood cell units received during hospitalization.
• Evaluating whether tocilizumab reduces the need for non-invasive respiratory support and invasive ventilation.
• Determining whether tocilizumab reduces readmission for vaso-occlusive crisis (VOC) or ACS within 3 months following injection.
• Assessing whether tocilizumab reduces biological inflammation markers such as C-reactive protein (CRP), procalcitonin (PCT), and IL-6 levels in plasma and sputum 48 hours after injection.
• Evaluating whether tocilizumab reduces pulmonary lesions on chest imaging 48 hours after injection.

The clinical trial involves participants diagnosed with **Sickle cell disease** (SCD), specifically those experiencing Acute Chest Syndrome (ACS). The study population includes both **male** and **female** subjects, with an age range starting from 2 years old. Participants are required to be hospitalized for ACS, characterized by fever and/or acute respiratory symptoms with a new pulmonary infiltrate on chest imaging. The trial includes individuals who require supplemental oxygen or respiratory support for less than 48 hours. The trial population was selected based on specific inclusion criteria, such as being an SCD patient of any genotype (SS, SC, S/β0, and S/β+), and having a negative pregnancy test for females of childbearing age. Participants must also provide informed consent and have social security or health insurance. The sponsor has not provided information regarding the total number of participants. The study considers vulnerable populations, and effective contraception is required up to six months post-treatment. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the **efficacy** and safety of **tocilizumab** in treating acute chest syndrome in patients with **sickle cell disease**. This is a phase III, randomized, double-blind, multicenter trial comparing **tocilizumab** to a placebo. The trial is expected to commence recruitment on October 1, 2024, and conclude by January 1, 2027. Participants will be randomly assigned to receive either **tocilizumab** or a placebo via intravenous infusion. The primary endpoint is the time to successful weaning from both supplemental oxygen and any respiratory support, defined as maintaining an SpO2 of 95% or higher without oxygen for 24 hours and spontaneous breathing without support for 48 hours.

Study visits will follow a structured sequence, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, hospitalization for acute chest syndrome, and the requirement for respiratory support. Participants must be at least 2 years old and have a confirmed diagnosis of **sickle cell disease**. Follow-up visits will monitor the participants' response to treatment and any adverse events. The end-of-study visit will evaluate the overall outcomes and collect final data. The expected length of participant involvement is up to one month, with conditions for early termination including withdrawal of consent, significant adverse events, or protocol non-compliance.

Participants will receive a single intravenous infusion of **tocilizumab** at a dose of 8 mg/kg for those weighing 30 kg or more, up to a maximum of 800 mg, and 12 mg/kg for those weighing less than 30 kg. The placebo group will receive an equivalent volume of sodium chloride solution. The trial will ensure that all participants provide informed consent and meet the inclusion criteria, including a negative pregnancy test for females of childbearing potential and effective contraception for six months post-treatment. The trial's rigorous design aims to provide robust data on the potential benefits of **tocilizumab** in this patient population.

The clinical trial involves the administration of **tocilizumab**, an experimental medication, to evaluate its efficacy in treating acute chest syndrome in patients with sickle cell disease. Tocilizumab is a monoclonal antibody classified under the ATC code L04AC07. It is administered as a single **intravenous infusion**. The dosage is determined based on the patient's weight: 8 mg/kg for patients weighing 30 kg or more, with a maximum dose of 800 mg, and 12 mg/kg for patients weighing less than 30 kg. The pharmaceutical form of tocilizumab is identified as PHF00231MIG. The treatment is administered once, and the maximum treatment period is one day.

In addition to the experimental treatment, the study utilizes a non-experimental treatment, **sodium chloride** 0.9% solution, which serves as a placebo. This solution is provided in an injectable ampoule form and is administered via **intravenous infusion**. The maximum daily and total dose of sodium chloride is 20 ml, and it is also administered over a single day. The sodium chloride solution is produced by B.BRAUN MELSUNGEN AG and is classified under the ATC code B05XA03. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

The clinical trial aims to assess the efficacy of **Tocilizumab** in treating Acute Chest Syndrome (ACS) in pediatric and adult patients with Sickle Cell Disease (SCD). The primary endpoint for evaluating efficacy is the "time to successful weaning from both supplemental oxygen and any respiratory support." This is defined as achieving an SpO2 of 95% or higher without supplemental oxygen for the subsequent 24 hours, and spontaneous breathing without any respiratory support, either non-invasive or invasive, for the following 48 hours. The trial involves a single intravenous infusion of Tocilizumab at a dose of 8 mg/kg for patients weighing 30 kg or more, with a maximum dose of 800 mg, and 12 mg/kg for patients weighing less than 30 kg.