A Phase 1b Randomized, Multicenter, Dose Determination Trial Of Zelpultide Alfa (recombinant human surfactant protein D, rhSP-D) In Preterm Neonates At High Risk Of Developing Bronchopulmonary Dysplasia

Almudena Alonso-Ojembarrena^1,2Brenda Poindexter³Samia Aleem⁴Helen Healy⁵Marta Aguar-Carrascosa^6,7Elisenda Moliner^8,9María Del Mar Serrano Martin¹⁰Raquel Arroyo¹¹MAXIMO VENTO^12*

• ¹Hospital Universitario Puerta del Mar, Cádiz, Spain
• ²Instituto de Investigacion e Innovacion Biomedica de Cadiz, Cádiz, Spain
• ³Emory University and Children’s Healthcare of Atlanta, Atlanta, United States
• ⁴Duke University Medical Center, Durham, United States
• ⁵Beth Israel Deaconess Medical Center, Boston, United States
• ⁶Hospital Universitari i Politecnic La Fe, Valencia, Spain
• ⁷Instituto de Investigacion Sanitaria La Fe, Valencia, Spain
• ⁸Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
• ⁹Institut de Recerca Sant Pau, Barcelona, Spain
• ¹⁰Hospital Regional Universitario de Malaga, Málaga, Spain
• ¹¹Airway Therapeutics Inc., Madrid, Spain
• ¹²La Fe Hospital, Valencia, Spain

Background: Bronchopulmonary dysplasia (BPD) ranks among the most severe long-term complications of prematurity . Surfactant Protein D, not present in commercial surfactant, regulates the innate immune response of the lungs by clearing infectious pathogens and limiting pulmonary inflammation and inflammatory injury. We aimed to assess the safety and tolerability of zelpultide alfa (rhSP-D) versus air-sham added to the standard of care in preterm neonates at risk of bronchopulmonary dysplasia (BPD). Efficacy was a secondary outcome.Methods: Phase 1b, randomized, double-blind, dose-determination study that enrolled intubated, mechanically-ventilated preterm neonates who required ≥ 1 surfactant treatment within 96 hours of birth. Initially, eight subjects (25-28 6 /7 weeks gestational age, GA) were randomized 3:1 to receive up to two doses of intratracheal zelpultide alfa at each dosing level (2, 4, or 6 mg/kg) or air-sham, 24 hours apart. Twelve additional subjects (23-28 6 /7 weeks GA) were randomized 3:1 to receive the highest-tolerated dose of zelpultide alfa, or air-sham, once daily for up to 7 days.Results: Thirty-seven subjects were randomized and treated. Zelpultide alfa, at its highest dose, 6 mg/kg had a favorable safety profile. 92.9% of zelpultide alfa subjects versus 100.0% air-sham experienced ≥ 1 adverse event. Mortality was 21% in the zelputide alfa group and 0% in the air-sham group, although no deaths were related to the study drug. The incidence of BPD was 32.1% vs 66.7%, BPD or death was 54% and 67%, and time on mechanical ventilation was 17.7 vs 25.8 days in the zelpultide alfa compared to the air-sham group.Conclusions: This study endorses the safety and tolerability of zelpultide alfa up to 6 mg/kg (≤ 7 days) and reinforces the need for further clinical development of zelpultide alfa as a therapy for preventing BPD.