Almudena Alonso-Ojembarrena, Brenda Poindexter, Samia Aleem, Helen Healy, Marta Aguar-Carrascosa, Elisenda Moliner-Calderón, María Del Mar Serrano-Martín, Raquel Arroyo, Maximo Vento
{"title":"zelpultide alfa（重组人表面活性剂蛋白D）用于支气管肺发育不良高危早产儿的1b期随机、多中心剂量测定试验","authors":"Almudena Alonso-Ojembarrena, Brenda Poindexter, Samia Aleem, Helen Healy, Marta Aguar-Carrascosa, Elisenda Moliner-Calderón, María Del Mar Serrano-Martín, Raquel Arroyo, Maximo Vento","doi":"10.3389/fped.2025.1639573","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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 vs. air-sham when added to the standard of care in preterm neonates at risk of BPD. Efficacy was a secondary outcome.</p><p><strong>Methods: </strong>A phase 1b, randomized, double-blind, dose-determination study was conducted that enrolled intubated, mechanically ventilated preterm neonates who required ≥1 surfactant treatment within 96 h of birth. Initially, eight subjects [25-28 <sup>6</sup>/<sub>7</sub> 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 h apart. Moreover, 12 additional subjects (23-28 <sup>6</sup>/<sub>7</sub> 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.</p><p><strong>Results: </strong>In total, 37 subjects were randomized and treated. Zelpultide alfa, at its highest dose of 6 mg/kg, had a favorable safety profile. Furthermore, 92.9% of zelpultide alfa subjects vs. 100.0% of those that received air-sham experienced ≥1 adverse event. The mortality rate was 21% in the zelpultide 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%, the incidence of BPD or death was 54% and 67%, and time on mechanical ventilation was 17.7 vs. 25.8 days in the zelpultide alfa group compared to the air-sham group, respectively.</p><p><strong>Conclusions: </strong>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.<b>Clinical Trial Registration</b>: https://clinicaltrials.gov/study/NCT04662151?cond=BPD&term=At-100&rank=1, identifier NCT04662151.</p>","PeriodicalId":12637,"journal":{"name":"Frontiers in Pediatrics","volume":"13 ","pages":"1639573"},"PeriodicalIF":2.0000,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465625/pdf/","citationCount":"0","resultStr":"{\"title\":\"A phase 1b randomized, multicenter, dose determination trial of zelpultide alfa (recombinant human surfactant protein D) in preterm neonates at high risk of developing bronchopulmonary dysplasia.\",\"authors\":\"Almudena Alonso-Ojembarrena, Brenda Poindexter, Samia Aleem, Helen Healy, Marta Aguar-Carrascosa, Elisenda Moliner-Calderón, María Del Mar Serrano-Martín, Raquel Arroyo, Maximo Vento\",\"doi\":\"10.3389/fped.2025.1639573\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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 vs. air-sham when added to the standard of care in preterm neonates at risk of BPD. Efficacy was a secondary outcome.</p><p><strong>Methods: </strong>A phase 1b, randomized, double-blind, dose-determination study was conducted that enrolled intubated, mechanically ventilated preterm neonates who required ≥1 surfactant treatment within 96 h of birth. Initially, eight subjects [25-28 <sup>6</sup>/<sub>7</sub> 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 h apart. Moreover, 12 additional subjects (23-28 <sup>6</sup>/<sub>7</sub> 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.</p><p><strong>Results: </strong>In total, 37 subjects were randomized and treated. Zelpultide alfa, at its highest dose of 6 mg/kg, had a favorable safety profile. Furthermore, 92.9% of zelpultide alfa subjects vs. 100.0% of those that received air-sham experienced ≥1 adverse event. The mortality rate was 21% in the zelpultide 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%, the incidence of BPD or death was 54% and 67%, and time on mechanical ventilation was 17.7 vs. 25.8 days in the zelpultide alfa group compared to the air-sham group, respectively.</p><p><strong>Conclusions: </strong>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.<b>Clinical Trial Registration</b>: https://clinicaltrials.gov/study/NCT04662151?cond=BPD&term=At-100&rank=1, identifier NCT04662151.</p>\",\"PeriodicalId\":12637,\"journal\":{\"name\":\"Frontiers in Pediatrics\",\"volume\":\"13 \",\"pages\":\"1639573\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2025-09-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465625/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Pediatrics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3389/fped.2025.1639573\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"PEDIATRICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Pediatrics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fped.2025.1639573","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"PEDIATRICS","Score":null,"Total":0}
A phase 1b randomized, multicenter, dose determination trial of zelpultide alfa (recombinant human surfactant protein D) in preterm neonates at high risk of developing bronchopulmonary dysplasia.
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 vs. air-sham when added to the standard of care in preterm neonates at risk of BPD. Efficacy was a secondary outcome.
Methods: A phase 1b, randomized, double-blind, dose-determination study was conducted that enrolled intubated, mechanically ventilated preterm neonates who required ≥1 surfactant treatment within 96 h 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 h apart. Moreover, 12 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: In total, 37 subjects were randomized and treated. Zelpultide alfa, at its highest dose of 6 mg/kg, had a favorable safety profile. Furthermore, 92.9% of zelpultide alfa subjects vs. 100.0% of those that received air-sham experienced ≥1 adverse event. The mortality rate was 21% in the zelpultide 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%, the incidence of BPD or death was 54% and 67%, and time on mechanical ventilation was 17.7 vs. 25.8 days in the zelpultide alfa group compared to the air-sham group, respectively.
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.Clinical Trial Registration: https://clinicaltrials.gov/study/NCT04662151?cond=BPD&term=At-100&rank=1, identifier NCT04662151.
期刊介绍：
Frontiers in Pediatrics (Impact Factor 2.33) publishes rigorously peer-reviewed research broadly across the field, from basic to clinical research that meets ongoing challenges in pediatric patient care and child health. Field Chief Editors Arjan Te Pas at Leiden University and Michael L. Moritz at the Children''s Hospital of Pittsburgh are supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
Frontiers in Pediatrics also features Research Topics, Frontiers special theme-focused issues managed by Guest Associate Editors, addressing important areas in pediatrics. In this fashion, Frontiers serves as an outlet to publish the broadest aspects of pediatrics in both basic and clinical research, including high-quality reviews, case reports, editorials and commentaries related to all aspects of pediatrics.
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