Clinical trial NCT06897839: Efficacy of Zelpultide Alfa in Preterm Neonates at High Risk of Developing Bronchopulmonary Dysplasia (BPD)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Bronchopulmonary Dysplasia
Keywords: BPD
Zelpultide alfa
AT-100
Lead sponsor: Airway Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2025-03-27
Enrollment: 316
Sex: ALL
Minimum age (years): 0
Maximum age (years): 96
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The goal of this Randomized, Double-Blind, Parallel-Group, Phase 3 Multicenter Study is to determine if an investigational drug, Zelpultide Alfa, can reduce the occurrence of Bronchopulmonary Dysplasia (BPD) in extremely premature babies.

The main objective is to compare the efficacy of zelpultide alfa added to standard of care (SOC) versus SOC plus placebo (air-sham) in terms of incidence of grade 2 and grade 3 bronchopulmonary dysplasia (BPD) and death in neonates at high risk for developing BPD.

Participants will be randomized 1:1 to the treatment (Zelpultide alfa plus standard of care) or placebo (air-sham plus standard of care) arms . Treatment will be administered intratracheally. Participants will receive up to 7 administrations of zelpultide alfa at 6 mg/kg or air-sham in 24 h intervals while the subjects are still intubated per standard of care.


Eligibility criteria: Inclusion Criteria:

1. Born between gestational age (GA) 23 0/7 to 27 6/7 weeks, inclusive.
2. Received at least 1 dose of SOC-indicated animal-derived pulmonary surfactant treatment after birth.
3. Intubated and on invasive mechanical ventilation per SOC.
4. Able to receive the first dose of zelpultide alfa or air-sham at least 15 min after the surfactant administration but within 96 h of birth and within 48 h from the start of invasive mechanical ventilation. Subjects extubated and re-intubated after their pulmonary surfactant dose(s) are eligible as long as the inclusion criteria are met.
5. Informed consent and personal information authorization form signed by the subject's parent(s) or legal guardian(s).

Exclusion Criteria:

1. Birth weight \< 400 g or \> 1,500 g.
2. Major apparent congenital abnormalities impacting cardio and pulmonary function identified before randomization, such as, but not limited to:

   * Clinically relevant Potter-like syndrome and any pulmonary congenital anomalies,
   * Clinically relevant congenital diaphragmatic hernia,
   * Omphalocele or gastroschisis, esophageal atresia,
   * Known or suspected cyanotic congenital heart disease (ie, tetralogy of fallot, transposition of the great arteries, etc).
3. Active do no resuscitate (DNR) order in place.
4. History of allergy or sensitivity to any surfactant or any component of zelpultide alfa.
5. Concurrent enrollment in any clinical study that utilizes treatments (investigational medical products or devices) outside of SOC or participation in studies within the last 30 days (or 5 half-lives of an IMP) prior to birth (for the mother) or up to week 36 PMA.
6. Any condition or situation that, in the Investigator's judgement, puts the neonate at significant risk, could confound the study results, or may interfere significantly with the neonate's participation in the study.

Primary outcomes:
measure: Incidence of grade 2 or grade 3 Bronchopulmonary Dysplasia (BPD) or death
timeFrame: Week 36 Post Menstrual Age (PMA)
Secondary outcomes:
measure: Ventilator-free days
timeFrame: From birth to 36 weeks Post Menstrual Age (PMA)
measure: Incidence of grade 2 or grade 3 Bronchopulmonary Dysplasia (BPD)
timeFrame: Week 36 Post Menstrual Age (PMA)
measure: Incidence of death
timeFrame: Week 36 Post Menstrual Age (PMA)
measure: The proportion of subjects with no Bronchopulmonary Dysplasia (BPD), grade 1, grade 2, or grade 3 BPD
timeFrame: Week 36 Post Menstrual Age (PMA)
measure: Ventilator-free days
timeFrame: From birth to day 28 of life
measure: Total average days on supplemental oxygen
timeFrame: From birth to 36 Weeks Post Menstrual Age (PMA)
measure: Total average days on continuous positive airway pressure (CPAP) or high flow nasal cannula (HFNC)
timeFrame: From birth to week 36 Post Menstrual Age (PMA)
measure: Extubation rate
timeFrame: Study Day 7
measure: Average preductal oxygen saturation measured by oxygen saturation index (OSI)
timeFrame: From Study Days 1 to 7
measure: Average preductal oxygen saturation measured by oxygen saturation to fraction of inspired oxygen ratio (SF)
timeFrame: From Study Days 1 to 7
measure: Survival at 6, 12 and 24 months corrected age
timeFrame: 6, 12 and 24 month corrected age
measure: Average number of hospitalizations and days in hospital
timeFrame: 6 and 12 months corrected age
measure: Incidence of chronic respiratory morbidity
timeFrame: 12 month corrected age
measure: Incidence of neurodevelopmental disability among survivors
timeFrame: 24 months corrected age
measure: Severity and frequency of treatment-emergent adverse events (TEAEs) or treatment-emergent serious adverse events (TESAEs)
timeFrame: From start of treatment through week 36 Post Menstrual Age (PMA) or hospital discharge, whichever comes first
Other outcomes:
measure: Incidence of grade 2 or grade 3 Bronchopulmonary Dysplasia (BPD) or death
timeFrame: Week 40 Post Menstrual Age (PMA)
measure: Incidence of grade 2 or grade 3 Bronchopulmonary Dysplasia (BPD)
timeFrame: Week 40 Post Menstrual Age (PMA)
measure: The proportion of subjects with no Bronchopulmonary Dysplasia (BPD), grade 1, grade 2, or grade 3 BPD
timeFrame: Week 40 Post Menstrual Age (PMA)
measure: Incidence of grade 2 or grade 3 Bronchopulmonary Dysplasia (BPD) or death after excluding subjects with death at ≤ 14 days postnatal age
timeFrame: Week 36 and week 40 Post Menstrual Age (PMA)
measure: Ventilator-free days
timeFrame: From birth to week 40 Post Menstrual Age (PMA)
Locations:
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Milano
country: Italy
facility: Ospedale dei Bambini "V. Buzzi"
city: Padova
country: Italy
facility: Azienda Ospedale Università di Padova
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante Dr. Balmis
city: Barakaldo, Bilbao
country: Spain
facility: Hospital Universitario Cruces - OSI Ezkerraldea-Enkarterri-Cruces
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Cádiz
country: Spain
facility: Hospital Universitario Puerta del Mar
city: Lleida
country: Spain
facility: Hospital Universitari Arnau de Vilanova de Lleida
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Málaga
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico Universitario de Santiago
city: Valencia
country: Spain
facility: Hospital Universitari i Politècnic La Fe
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
Study officials:
References: