Long-Term Safety Evaluation of Oxytocin Nasal Spray in Children with Prader-Willi Syndrome from the OTBB3 Trial

The primary objective of this study is to confirm the long-term **safety** profile, including the associated main comorbidities, in all children with **Prader-Willi syndrome** (PWS) who have been treated in the OTBB3 study. This objective is clinically relevant as it aims to ensure the continued safety of therapeutic interventions in a vulnerable pediatric population, potentially impacting treatment guidelines and patient management strategies for PWS.

The clinical trial involves a study population of children diagnosed with **Prader-Willi syndrome** (PWS). The trial includes both male and female participants, indicating a mixed-gender cohort. The age range for the treated cohort is approximately 16 months, while the untreated cohort includes children around 30 months of age. Participants are selected based on a genetically confirmed diagnosis of PWS, and the trial includes both children who have previously participated in the OTBB3 study and those who have not received the treatment. The trial population is considered vulnerable due to the young age of the participants. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed as a **randomized**, double-blind, controlled study to evaluate the long-term safety profile of **oxytocin** administered as a nasal spray solution in children with **Prader-Willi syndrome**. The trial will span a period of approximately four years, with the estimated end date set for June 1, 2025. Participants will be divided into two cohorts: a treated cohort, consisting of children who previously participated in the OTBB3 study, and an untreated cohort, comprising children who have never received oxytocin. The primary objective is to assess the number and percentage of patients experiencing adverse events and serious adverse events, as well as the occurrence of main comorbidities and any medications, surgeries, or rehabilitations undertaken.

The sequence of study visits includes an initial inclusion (screening) visit, followed by routine follow-up visits, and concludes with an end-of-study visit. The inclusion visit will be aligned with the next routine consultation for both cohorts. The treated cohort will include children aged 16±4 months, while the untreated cohort will include children aged 30±6 months. The expected length of participant involvement is up to four years, with regular assessments to monitor safety and efficacy. Conditions that may lead to early termination from the study include the occurrence of significant adverse events or withdrawal of consent by the parents or legal representatives.

Participants will receive the **Otwillo 44.44 IU/mL** nasal spray solution, with a maximum daily dose of 4 units, administered intranasally. The trial is categorized as a Phase 4 study, focusing on the observation of long-term efficacy and safety of the treatment. The study will not include any pediatric-specific formulations, and the product is not classified as an orphan drug. The trial aims to provide comprehensive data on the long-term impact of oxytocin treatment in children with Prader-Willi syndrome, contributing valuable insights into the management of this rare condition.

The clinical trial involves the administration of **Otwillo 44.44 IU/mL**, a **nasal spray solution** containing the active substance **oxytocin**. This pharmaceutical form is specifically designed for **intranasal use**. The dosage regimen for this experimental medication is set at a maximum daily dose of 4 IU, with the total dose not exceeding 4 IU per day. The treatment period is limited to a maximum of 8 weeks. The oxytocin used in this formulation is derived from a protein of other origin, and the product is classified as a biochemical product. The administration of the nasal spray is intended to be monitored for compliance throughout the study duration.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is on evaluating the long-term safety profile of the experimental medication in children with Prader-Willi Syndrome who have previously participated in the OTBB3 clinical trial. The study aims to confirm the safety and monitor any associated main comorbidities in the treated cohort compared to an untreated cohort. Participant compliance with the dosing schedule will be closely monitored to ensure adherence to the prescribed regimen.

Efficacy in this clinical trial will be assessed through the evaluation of primary endpoints, which include the number and percentage of patients experiencing adverse events (AEs) and serious adverse events (SAEs), as well as the occurrence of main comorbidities. Additionally, the trial will monitor the occurrence of medications, surgeries, and rehabilitations by collecting data on type, age at start and stop, dosing, or frequency. These parameters will provide insights into the long-term safety profile of the treatment in children with **Prader-Willi Syndrome** (PWS) who participated in the OTBB3 study.