Efficacy and Safety of Zelpultide Alfa in Preterm Neonates at High Risk of Developing Bronchopulmonary Dysplasia (BPD)

Phase 3RecruitingNCT06897839

Airway Therapeutics, Inc.366 enrolled

Overview

This is a randomized, parallel-group, double-blind, placebo-controlled multicenter phase 2b/3 study with an adaptive seamless design. The goal fo this study is to determine if an investigational drug, Zelpultide Alfa, can reduce the occurrence of Bronchopulmonary Dysplasia (BPD) in extremely premature babies. The study comprises 2 parts: * Part 1: Phase 2b, dose selection and exploratory efficacy and safety. * Part 2: Phase 3, confirmatory efficacy and safety. In Part 1, the study subjects will be randomized with a 1:1:1 allocation ratio to either : 1. Standard of care + zelpultide alfa 4 mg/kg or, 2. Standard of care + zelpultide alfa 6 mg/kg or, 3. Standard of care + placebo (air-sham). In Part 1, all three arms will be evaluated descriptively to support dose selection based on safety, tolerability, and exploratory efficacy signals. Upon completion of Part 1, the DSMC will recommend which Phase 2b dose ("selected dose") to progress into Part 2 to the Study Steering Committee, which will decide the dose for Part 2 (Phase 3). A sample size reassessment will be performed after Part 1 completion. In Part 2, the selected dose of zelpultide alfa will be compared against placebo (air-sham) in a confirmatory analysis on the primary and key secondary endpoints. The study subjects will be randomized with a 1:1 allocation ratio to either: 1. Standard of care + zelpultide alfa (selected dose from Part 1), or 2. Standard of care + placebo (air-sham). The main objective in part 2 is to compare the efficacy of zelpultide alfa added to standard of care versus standard of care 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. In both parts, treatment will be administered intratracheally. Participants will receive up to 7 administrations of zelpultide alfa at (4mg/kg or 6 mg/kg) or air-sham in 24 h intervals while the subjects are still intubated per standard of care.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Eligibility

Sex: ALLMin age: 0 MinutesMax age: 96 Hours

Medical Language ↔ Plain English

Inclusion Criteria: 1. Born between gestational age (GA) 22 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.

Locations (50)

Clínica y Maternidad Suizo Argentina

Buenos Aires, Argentina

RECRUITING

Hospital Italiano de Buenos Aires

Buenos Aires, Argentina

RECRUITING

Hospital Sanatorio de la Trinidad San Isidro

Buenos Aires, Argentina

RECRUITING

Hospital Universitario Austral

Buenos Aires, Argentina

Outcomes

Primary Outcomes

Incidence of grade 2 or grade 3 Bronchopulmonary Dysplasia (BPD) or death

BPD is defined and graded based on the classification according to Jensen et al., 2019 (2019 PMID: 30995069)

Time frame: Week 36 Post Menstrual Age (PMA)

Secondary Outcomes

Ventilator-free days

A ventilator-free day is defined as a natural calendar day without being on invasive mechanical ventilation (ie, invasive ventilation via ETT or tracheostomy); tracheostomy will be treated as all invasive ventilation.

Time frame: From birth to 36 weeks Post Menstrual Age (PMA)

Incidence of grade 2 or grade 3 Bronchopulmonary Dysplasia (BPD)

Time frame: Week 36 Post Menstrual Age (PMA)

Incidence of death

Time frame: Week 36 Post Menstrual Age (PMA)

Incidence of grade 2 or grade 3 Bronchopulmonary Dysplasia (BPD) or death assessed on 3 consecutive days at week 36 PMA

BPD is defined and graded based on the classification according to Jensen et al., 2019 (2019 PMID: 30995069)

Time frame: Week 36 Post Menstrual Age (PMA)

The proportion of subjects with no Bronchopulmonary Dysplasia (BPD), grade 1, grade 2, or grade 3 BPD

BPD is defined and graded based on the classification according to Jensen et al., 2019 (2019 PMID: 30995069)

Time frame: Week 36 Post Menstrual Age (PMA)

The proportion of subjects with no Bronchopulmonary Dysplasia (BPD), grade 1, grade 2, or grade 3 BPD assessed on 3 consecutive days at week 36 PMA

BPD is defined and graded based on the classification according to Jensen et al., 2019 (2019 PMID: 30995069)

Time frame: Week 36 Post Menstrual Age (PMA)

Ventilator-free days

Time frame: From birth to day 28 of life

Total average days on supplemental oxygen

Time frame: From birth to 36 Weeks Post Menstrual Age (PMA)

Total average days on continuous positive airway pressure (CPAP) or high flow nasal cannula (HFNC)

Time frame: From birth to week 36 Post Menstrual Age (PMA)

Extubation rate

Time frame: Study Day 7

Average preductal oxygen saturation measured by oxygen saturation to fraction of inspired oxygen ratio (SF)

Time frame: From Study Days 1 to 7

Average preductal oxygen saturation measured by oxygen saturation index (OSI)

Time frame: From Study Days 1 to 7

Incidence of grade 2 or grade 3 Bronchopulmonary Dysplasia (BPD) or death

BPD is defined and graded based on the classification according to Jensen et al., 2019 (2019 PMID: 30995069)

Time frame: Week 40 Post Menstrual Age (PMA)

Incidence of grade 2 or grade 3 Bronchopulmonary Dysplasia (BPD)

BPD is defined and graded based on the classification according to Jensen et al., 2019 (2019 PMID: 30995069)

Time frame: Week 40 Post Menstrual Age (PMA)

The proportion of subjects with no Bronchopulmonary Dysplasia (BPD), grade 1, grade 2, or grade 3 BPD

BPD is defined and graded based on the classification according to Jensen et al., 2019 (2019 PMID: 30995069)

Time frame: Week 40 Post Menstrual Age (PMA)

Incidence of grade 2 or grade 3 Bronchopulmonary Dysplasia (BPD) or death after excluding subjects with death at ≤ 14 days postnatal age

BPD is defined and graded based on the classification according to Jensen et al., 2019 (2019 PMID: 30995069)

Time frame: Week 36 and week 40 Post Menstrual Age (PMA)

Ventilator-free days

Time frame: From birth to week 40 Post Menstrual Age (PMA)

Survival at 6, 12 and 24 months corrected age

Time frame: 6, 12 and 24 month corrected age

Average number of hospitalizations and days in hospital

Time frame: 6 and 12 months corrected age

Incidence of chronic respiratory morbidity

Time frame: 12 month corrected age

Incidence of neurodevelopmental disability among survivors

Time frame: 24 months corrected age

Severity and frequency of treatment-emergent adverse events (TEAEs) or treatment-emergent serious adverse events (TESAEs)

Time frame: From start of treatment through week 36 Post Menstrual Age (PMA) or hospital discharge, whichever comes first

Immunogenicity analysis

Determination of anti-SP-D antibodies in blood at day 28 of life compared to baseline), assessed in a subset of 60 patients

Time frame: Day 28 of life

Efficacy and Safety of Zelpultide Alfa in Preterm Neonates at High Risk of Developing Bronchopulmonary Dysplasia (BPD)

Overview

Conditions

Interventions

Eligibility

Locations (50)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts