FAMODREP : Interest of Famotidine in Reducing Endothelial Expression of P-selectin in Children With Sickle Cell Disease: Pilot Study, Single-center, Prospective, Non-comparative

The primary objective of this study is to evaluate the effect of **famotidine** on the expression of **P-selectin** after 29 days of treatment in children with **Sickle Cell Disease**. P-selectin is a critical marker of endothelial activation, and its reduction could potentially mitigate vascular complications associated with this condition, thereby improving clinical outcomes.

Secondary objectives include:

• Assessing the effect of famotidine on the expression of other endothelial activation markers after 29 days of treatment.
• Evaluating the impact of famotidine on biomarkers of hemolysis and inflammation after 29 days of treatment.
• Investigating the adverse effects of famotidine in a pediatric population suffering from sickle cell disease.
• Assessing the occurrence of CVO (cerebrovascular occlusion).

The clinical trial involves participants diagnosed with **Sickle Cell Disease**, specifically targeting a pediatric population. The study includes both male and female subjects, ranging in age from 1 year to 17 years and 10 months. Participants are required to have experienced at least one vaso-occlusive crisis in the year prior to inclusion. The trial population was selected from individuals followed at the Necker-Enfants Malades Hospital, with a focus on those with major sickle cell syndrome SS or Sβ0. The sponsor has not provided information regarding the total number of participants. Key lifestyle considerations, such as diet and physical activity, are not specified. The study does not involve a vulnerable population, and all participants must have social security coverage or be entitled to it. For young girls of childbearing age, a negative pregnancy test is required. Informed consent from both parents or legal representatives, as well as from the child or adolescent when possible, is mandatory.

The clinical trial is designed to evaluate the effect of **famotidine** on the expression of P-selectin in children with **Sickle Cell Disease**. This is a single-center, prospective, non-comparative study. The trial will involve a treatment period of 29 days, during which participants will receive famotidine in the form of an oral suspension. The study aims to assess the primary endpoint, which is the difference in plasma concentration of soluble P-selectin, measured using the ELISA technique, before and after the treatment period. Secondary endpoints include changes in plasma concentrations of soluble adhesion molecules such as E-selectin, VCAM-1, and ICAM-1, as well as blood values of hemoglobin, reticulocytes, ASAT, free bilirubin, LDH, and CRP. The occurrence of serious or non-serious adverse events and vaso-occlusive crises will also be monitored.

Participants will be children or adolescents aged 1 to 17 years and 10 months, who have experienced at least one vaso-occlusive crisis in the year prior to inclusion. The inclusion visit will involve screening to ensure eligibility based on the criteria, including a negative pregnancy test for females of childbearing age and signed informed consent from parents or legal representatives. The trial will commence with a baseline visit to collect initial data, followed by regular follow-up visits to monitor the participants' health and response to the treatment. The end-of-study visit will occur after the 29-day treatment period to collect final data and assess the primary and secondary endpoints.

The expected duration of participant involvement is approximately 29 days, with the possibility of early termination if adverse events occur or if the participant withdraws consent. The trial is categorized as a Phase IV therapeutic use study, focusing on the safety and efficacy of famotidine in the specified patient population. The study is not classified as low intervention, and the maximum daily dose of famotidine is set at 80 mg. Participants will be closely monitored throughout the trial to ensure their safety and the integrity of the study data.

The clinical trial involves the administration of **famotidine**, a competitive inhibitor of histamine-2 (H2) receptors, as the experimental medication. Famotidine is provided in the form of an **oral suspension**. The active substance, famotidine, is of chemical origin and is identified by the EU substance number SUB07503MIG. The maximum daily dose of famotidine administered to participants is 80 mg, with the total dose not exceeding 80 mg per day. The treatment period is set for a maximum of 29 days. The route of administration is oral, and the medication is not formulated specifically for pediatric use. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are utilized in this study. The trial is designed to assess the effect of famotidine on P-selectin expression in children with sickle cell disease over the specified treatment period. Participants' adherence to the dosing schedule is closely monitored to ensure the integrity of the trial results.

The efficacy of famotidine in reducing endothelial expression of **P-selectin** in children with sickle cell disease will be assessed through a primary endpoint and several secondary endpoints. The primary endpoint involves measuring the difference in plasma concentration of soluble **P-selectin** using the ELISA technique (Human P-selectin / CD62P Quantikine ELISA kit, R&D) before and after 29 days of treatment with famotidine. Secondary endpoints include evaluating the differences in plasma concentrations of soluble adhesion molecules such as E-selectin, VCAM-1, and ICAM-1, also measured by ELISA techniques (Human E-selectin / CD62E, Human sVCAM-1 / CD106, and Human ICAM-1 / CD54 Quantikine ELISA kits, R&D) before and after the treatment period.

Additional secondary endpoints will assess changes in blood values of hemoglobin, reticulocytes, ASAT, free bilirubin, LDH, and CRP, which will be measured in the hematology/hemostasis and biochemistry laboratories of the Necker-Enfants Malades Hospital. The occurrence of serious or non-serious adverse events and the occurrence of vaso-occlusive crises (CVO) will also be monitored. These assessments will be conducted at baseline and after the 29-day treatment period to determine the efficacy of famotidine in this patient population.