Evaluation of Retinol Palmitate Administration and Serum Levels in Preterm Infants with Bronchopulmonary Dysplasia: A Phase 2a Open-Label Study

The primary objectives of this study are to assess **Retinol** serum concentration at Days 0 and 28 in preterm infants with gestational age (GA) between 22 weeks + 0 day and 29 weeks + 6 days, and to evaluate the safety and tolerability of RetinolX from Day 0 to week 36 post-menstrual age (PMA). These objectives are clinically relevant as they aim to determine the appropriate dosing and safety profile of RetinolX, a new pediatric formulation, in a vulnerable population at risk for **Bronchopulmonary Dysplasia**.

The secondary objectives include:

• Assessing the relative increase of retinol serum concentration to 60% at Day 28.
• Analyzing retinol serum concentration at Day 7 and Day 14.
• Evaluating the need for respiratory support and/or oxygen at 28 days postnatal age.
• Assessing the need for respiratory support and/or oxygen at 36 weeks + 0 day PMA.

The clinical trial focuses on **Bronchopulmonary Dysplasia** in a vulnerable population of preterm infants. The study population includes both male and female infants with a gestational age (GA) of less than 30 weeks. Specifically, the trial involves 12 very preterm infants, comprising 7 extremely preterm infants with a GA of 27 weeks + 6 days or less, and 5 very preterm infants with a GA between 28 weeks + 0 day and 29 weeks + 6 days. Participants are enrolled between 24 and 72 hours after birth. The trial does not specify any particular lifestyle considerations such as diet or physical activity, given the age and condition of the participants. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is a **Phase 2a**, open-label, single-arm study designed to investigate the tolerability of intravenous (IV) or intramuscular (IM) administration of RetinolX, a formulation of **retinol palmitate**, in preterm infants diagnosed with **bronchopulmonary dysplasia**. The primary objectives are to assess the serum concentration of retinol at Days 0 and 28 and to evaluate the safety and tolerability of RetinolX from Day 0 to week 36 post-menstrual age (PMA). The trial is expected to commence on March 31, 2025, and conclude by March 31, 2026.

The study will involve a sequence of visits, beginning with an inclusion (screening) visit, where eligibility criteria are confirmed. Participants will be preterm infants with a gestational age (GA) of less than 30 weeks, enrolled between 24 and 72 hours after birth. The trial will include follow-up visits to monitor serum retinol levels and safety parameters at Days 7, 14, and 28, with additional assessments at 36 weeks PMA. The end-of-study visit will occur at 36 weeks PMA, marking the completion of the trial for each participant.

Participants are expected to be involved in the study for a maximum of 4 weeks, with the possibility of early termination if significant adverse events occur or if the participant's condition necessitates withdrawal. The primary endpoints include the relative increase in serum retinol levels at Day 28 compared to baseline and the incidence of treatment-emergent adverse events (TEAEs) throughout the study. Secondary endpoints focus on the percentage of subjects with a 60% increase in serum retinol levels and the need for respiratory support at specified time points. The trial aims to provide valuable insights into the efficacy and safety of RetinolX in this vulnerable population.

The clinical trial involves the administration of **RetinolX**, a new pediatric formulation of **retinol palmitate**, which is an **orphan drug**. The pharmaceutical form of the experimental medication is a **solution for injection**. The active substance, **retinol palmitate**, is of chemical origin and is provided by Aspire Pharma Limited. The medication is administered either intravenously (IV) or intramuscularly (IM) to preterm infants. The dosing regimen specifies a maximum daily dose of 4750 IU/ml and a maximum total dose of 5250 IU/ml over a treatment period of up to 4 weeks. The study aims to assess the serum concentration of retinol at Days 0 and 28, as well as to evaluate the safety and tolerability of RetinolX from Day 0 to week 36 post-menstrual age (PMA).

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the administration of RetinolX to evaluate its effects and safety profile in the specified patient population. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol and to accurately assess the outcomes related to the administration of RetinolX.

Efficacy in this clinical trial will be assessed primarily by measuring the relative increase in serum **retinol** levels at Day 28 compared to baseline in preterm infants. Secondary efficacy endpoints include the percentage of subjects with a relative increase of 60% in serum retinol levels between Day 0 and Day 28, as well as the relative increase in serum retinol levels at Day 7 and Day 14 compared to baseline. Additionally, the trial will evaluate the percentage of subjects requiring respiratory support and/or oxygen at 28 days postnatal age and at 36 weeks + 0 day post-menstrual age (PMA).

The serum levels of **retinol**, **retinol palmitate**, and **retinol binding protein** (RBP4) will be measured at specified time points, including Days 0, 7, 14, and 28. These measurements will be conducted using validated laboratory tests to ensure accuracy and reliability. The data collected will be analyzed to determine the efficacy of the new pediatric formulation, RetinolX, in increasing serum retinol levels and reducing the need for respiratory support in the target population of preterm infants.