Efficacy of Zelpultide Alfa in Preventing Bronchopulmonary Dysplasia in High-Risk Preterm Neonates: A Phase 3 Randomized, Double-Blind, Multicenter Study

The primary objective of this study is to evaluate the **efficacy** of zelpultide alfa, when added to standard of care (SOC), compared to SOC plus placebo (air-sham) in reducing the incidence of grade 2 and grade 3 **bronchopulmonary dysplasia** (BPD) and mortality in neonates at high risk for developing BPD. This is clinically relevant as BPD is a serious lung condition affecting premature infants, and reducing its incidence can significantly improve neonatal outcomes and survival rates.

Secondary objectives include:

• Comparing the efficacy of zelpultide alfa in terms of the incidence of BPD and death in high-risk neonates.
• Assessing the incidence of respiratory comorbidities associated with prematurity and late neurodevelopmental outcomes between the zelpultide alfa group and the SOC plus placebo group.
• Evaluating medical resource utilization and other health economic parameters between the two groups in neonates at high risk for developing BPD.

The clinical trial focuses on neonates at high risk for developing **bronchopulmonary dysplasia** (BPD), specifically targeting those born between gestational ages 23 0/7 to 27 6/7 weeks. The study population includes both male and female subjects, and it is acknowledged as a vulnerable population due to the age and health status of the participants. The trial does not specify the total number of participants, as this information was not provided by the sponsor. Participants are required to have received at least one dose of standard-of-care animal-derived pulmonary surfactant treatment after birth and must be intubated and on invasive mechanical ventilation. The trial population was selected based on these criteria, and informed consent must be obtained from the subject's parent(s) or legal guardian(s). The study does not specify any particular lifestyle considerations such as diet or physical activity, given the age and condition of the participants.

The clinical trial is designed as a **randomized, double-blind, parallel-group, Phase 3 multicenter study** to evaluate the efficacy of **zelpultide alfa** in preventing **bronchopulmonary dysplasia (BPD)** in high-risk preterm neonates compared to standard of care (SOC). The trial aims to compare the efficacy of zelpultide alfa added to SOC versus SOC plus placebo (air-sham) in terms of the incidence of grade 2 and grade 3 BPD and death in neonates at high risk for developing BPD. The trial is expected to commence recruitment on October 1, 2024, and conclude by March 1, 2027.

Participants will be involved in the study for a maximum treatment period of 7 days, with the primary endpoint being the incidence of grade 2 or grade 3 BPD or death at week 36 postmenstrual age (PMA). Secondary endpoints include ventilator-free days from birth to week 36 PMA, incidence of grade 2 or grade 3 BPD at week 36 PMA, and incidence of death at week 36 PMA. The study will include an initial screening visit to confirm eligibility based on criteria such as gestational age between 23 0/7 to 27 6/7 weeks, receipt of at least one dose of SOC-indicated animal-derived pulmonary surfactant treatment, and intubation with invasive mechanical ventilation per SOC.

Following the screening, eligible participants will receive either zelpultide alfa or air-sham at least 15 minutes after surfactant administration but within 96 hours of birth and within 48 hours from the start of invasive mechanical ventilation. Study visits will be scheduled to monitor the participants' health status and treatment efficacy, with the end-of-study visit occurring at week 36 PMA. Participants may be withdrawn from the study if they do not meet the inclusion criteria, experience adverse events, or if consent is withdrawn by the parent(s) or legal guardian(s). The trial is not categorized as low intervention and is conducted under strict regulatory and ethical guidelines to ensure participant safety and data integrity.

The clinical trial involves the administration of **zelpultide alfa**, an experimental medication, to evaluate its efficacy in preventing **bronchopulmonary dysplasia** (BPD) in high-risk preterm neonates. Zelpultide alfa is formulated as an endotracheopulmonary instillation solution and is administered via the endotracheopulmonary route. The active substance in zelpultide alfa is **recombinant human surfactant protein-D**. The dosing regimen for zelpultide alfa is specified as a maximum daily dose of 6 mg/kg, with a total maximum dose of 42 mg/kg over a treatment period of up to 7 days. The pharmaceutical form is specifically designed for endotracheopulmonary use, ensuring targeted delivery to the lungs.

In addition to the experimental treatment, the study includes a **placebo** group, which receives an endotracheopulmonary instillation of room air, serving as an air-sham comparator. This placebo is administered in the same manner as the experimental drug to maintain the double-blind nature of the trial. The placebo is used to assess the efficacy of zelpultide alfa when added to the standard of care (SOC) therapy, which is provided to all participants. The SOC therapy is not specified in the trial data but typically includes treatments commonly used in clinical practice for managing high-risk preterm neonates.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol. The trial is designed to compare the incidence of grade 2 and grade 3 BPD and mortality rates between the zelpultide alfa group and the placebo group, providing insights into the potential benefits of the experimental treatment in this vulnerable population.

The efficacy of zelpultide alfa in preventing **Bronchopulmonary Dysplasia (BPD)** in high-risk preterm neonates will be assessed through a randomized, double-blind, parallel-group, Phase 3 multicenter study. The primary endpoint for evaluating efficacy is the incidence of grade 2 or grade 3 BPD or death at week 36 postmenstrual age (PMA). Secondary endpoints include the number of ventilator-free days from birth to week 36 PMA, the incidence of grade 2 or grade 3 BPD at week 36 PMA, and the incidence of death at week 36 PMA.

Measurements will be collected at specified timepoints, with the primary endpoint assessed at week 36 PMA. The study will compare the efficacy of zelpultide alfa added to standard of care (SOC) versus SOC plus placebo (air-sham). The trial is designed to ensure that data collection and analysis are conducted in a manner that maintains the integrity and reliability of the results. The study will follow a rigorous protocol to ensure that all efficacy parameters are accurately measured and analyzed.