A Randomized, Open-Label Study on Palivizumab Prophylaxis for Prevention of Respiratory Morbidity in Preterm Infants with RSV Bronchiolitis

The primary objective of this study is to compare the incidence rate of overall **respiratory morbidity** in otherwise healthy preterm infants born between 29+0 and 35+6 weeks of gestational age. The comparison is between those exposed to prophylaxis with **palivizumab** (Group A) and those not exposed to this prophylaxis (Group B). This objective is clinically relevant as it aims to determine the effectiveness of palivizumab in reducing respiratory complications in preterm infants, which can have significant implications for their long-term health outcomes.

Secondary objectives include:

• Evaluating the difference in **RSV-related hospitalization** due to lower respiratory infections during the first RSV season (November 1st to March 31st) between Group A and Group B.
• Assessing direct and indirect costs related to respiratory sequelae in both groups. This includes collecting data on hospitalization length, need for mechanical ventilation and other support therapies, intensive care unit admissions and length of stay, medical specialist visits, drug usage, diagnostic exams, and parental workdays lost due to child illness.

The clinical trial involves a study population of **preterm infants** aged 29+0 to 35+6 weeks gestational age (wGA), both male and female, who are otherwise healthy and do not exhibit any major short- or long-term morbidity related to prematurity. Participants are younger than 6 months of age at the onset of the **Respiratory Syncytial Virus (RSV)** season, which begins on November 1st. The trial includes a vulnerable population, as it involves neonates. The sponsor has not provided information regarding the total number of participants. The trial population was selected based on specific inclusion criteria, including the requirement for written informed consent obtained from parents or legal guardians. The study does not specify any particular lifestyle considerations such as diet or physical activity for the participants.

The clinical trial is a **randomized**, multicenter, open-label study designed to evaluate the efficacy of **palivizumab** in preventing respiratory sequelae of **respiratory syncytial virus (RSV) bronchiolitis** in preterm infants. The trial involves two groups: Group A, which receives prophylaxis with palivizumab, and Group B, which does not receive the prophylaxis. The primary objective is to compare the incidence rate of overall respiratory morbidity between these groups. The study is expected to run from June 29, 2020, to June 29, 2025, with participant involvement lasting up to five months, corresponding to the RSV season from November 1st to March 31st.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as being a healthy preterm infant aged 29+0 to 35+6 weeks gestational age and younger than six months at the start of the RSV season. Written informed consent must be obtained from parents or legal guardians. Follow-up visits will occur throughout the RSV season to monitor health status and collect data on respiratory morbidity, including lower respiratory tract infections and recurrent wheezing. The end-of-study visit will assess the primary and secondary endpoints, including the difference in RSV-related hospitalizations and healthcare resource utilization between the two groups.

Participants may be withdrawn from the study if they experience adverse events related to the intervention, if they no longer meet the inclusion criteria, or if consent is withdrawn by the parents or guardians. The trial's primary endpoint is the overall respiratory morbidity, defined as lower respiratory tract infections by any pathogen and recurrent wheezing. Secondary endpoints include the difference in RSV-related hospitalizations and the direct and indirect costs associated with healthcare resource use and parental work loss due to child illness. The trial is conducted under the sponsorship of AstraZeneca AB, with the investigational product being Synagis 50 mg/0.5 ml solution for injection, administered via injection.

The clinical trial involves the administration of **palivizumab**, marketed under the name Synagis, which is a **solution for injection**. This experimental medication is provided in a concentration of 50 mg/0.5 ml. The pharmaceutical form is a solution intended for injection, and the route of administration is via injection. The dosage is calculated based on the participant's weight, with a maximum daily dose of 15 mg/kg. The treatment is administered once every month, with a maximum treatment period of 5 months. The active substance, palivizumab, is a protein-based therapeutic agent, specifically classified under the ATC code J06BB16. The medication is produced by AstraZeneca AB and is not formulated specifically for pediatric use, although it is used in a pediatric population in this study.

In this study, the experimental group (Group A) receives prophylaxis with palivizumab, while the control group (Group B) does not receive this prophylaxis. There is no mention of a placebo or other comparator treatments being used in this trial. The study aims to compare the incidence rate of overall respiratory morbidity in preterm babies who are otherwise healthy. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment protocol. The trial is designed to assess the efficacy of palivizumab in preventing respiratory sequelae of RSV bronchiolitis in preterm infants.

Efficacy in the clinical trial titled "Randomized, multicenter, open-label study on PREvention of respiratory SEquelae of RSV bronchiolitis in preterm babies (PRESERV)" will be assessed using both primary and secondary endpoints. The primary endpoint is the overall respiratory morbidity, which is a composite measure including **lower respiratory tract infections (LRTIs)** by any pathogen and recurrent wheezing, quantified by the presence of wheezing days and/or the need for antiwheezing drugs, with or without asthma. Secondary endpoints include the difference in the number of RSV-related hospitalizations due to low respiratory tract infection during the first RSV season between the two groups, as well as direct and indirect costs associated with health resource utilization and loss of working days due to child illness.

The trial will compare the incidence rate of overall respiratory morbidity in otherwise healthy preterm babies aged 29+0 to 35+6 weeks gestational age (wGA) who are exposed to prophylaxis with **palivizumab** (Group A) versus those not exposed (Group B). The study will collect data on hospitalizations, mechanical ventilation, ICU admissions, outpatient visits, drug usage, and diagnostic tests to evaluate direct costs, while indirect costs will be assessed based on the loss of working days. The trial is designed as a phase 3, open-label, randomized, and controlled study, with the estimated recruitment start date being June 29, 2020, and the estimated end date being June 29, 2025.