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

Not Applicable

Active, not recruiting

• Conditions: Bronchopulmonary Dysplasia
• Interventions: Drug: Zelpultide alfa; Other: Air-sham

• Registration Number: NCT06897839
• Lead Sponsor: Airway Therapeutics, Inc.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2025-02-03
• Study First Submitted: 2025-02-20
• Study First Submitted QC: 2025-03-20
• Study First Posted: 2025-03-27
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-10
• Last Update Posted: 2025-09-16
• Primary Completion: 2027-12-31
• Study Completion: 2030-02-28

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 366

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Zelpultide alfa 4 mg/kg plus standard of care	Zelpultide alfa	In addition to the preterm neonate standard of care, the subjects randomized to this treatment arm will receive up to 7 administrations of zelpultide alfa at 4 mg/kg (birth weight) in 24 h intervals while the subjects are still intubated.
Placebo (air-sham) plus standard of care	Air-sham	In addition to the preterm neonate standard of care, approximately 1 mL of air drawn into a dosing syringe will be administered up to 7 times to neonate subjects randomized to the control (placebo) arm, following the same means and intervals as in the treatment arm.
Zelpultide alfa 6 mg/kg plus standard of care	Zelpultide alfa	In addition to the preterm neonate standard of care, the subjects randomized to this treatment arm will receive up to 7 administrations of zelpultide alfa at 6 mg/kg (birth weight) in 24 h intervals while the subjects are still intubated.

Primary Outcome Measures

Name	Time	Method
Incidence of grade 2 or grade 3 Bronchopulmonary Dysplasia (BPD) or death	Week 36 Post Menstrual Age (PMA)	BPD is defined and graded based on the classification according to Jensen et al., 2019 (2019 PMID: 30995069)

Secondary Outcome Measures

Name	Time	Method
Ventilator-free days	From birth to week 40 Post Menstrual Age (PMA)	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.
Incidence of grade 2 or grade 3 Bronchopulmonary Dysplasia (BPD)	Week 40 Post Menstrual Age (PMA)	BPD is defined and graded based on the classification according to Jensen et al., 2019 (2019 PMID: 30995069)
Incidence of death	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	Week 36 Post Menstrual Age (PMA)	BPD is defined and graded based on the classification according to Jensen et al., 2019 (2019 PMID: 30995069)
The proportion of subjects with no Bronchopulmonary Dysplasia (BPD), grade 1, grade 2, or grade 3 BPD	Week 40 Post Menstrual Age (PMA)	BPD is defined and graded based on the classification according to Jensen et al., 2019 (2019 PMID: 30995069)
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	Week 36 Post Menstrual Age (PMA)	BPD is defined and graded based on the classification according to Jensen et al., 2019 (2019 PMID: 30995069)
Total average days on supplemental oxygen	From birth to 36 Weeks Post Menstrual Age (PMA)
Total average days on continuous positive airway pressure (CPAP) or high flow nasal cannula (HFNC)	From birth to week 36 Post Menstrual Age (PMA)
Extubation rate	Study Day 7
Average preductal oxygen saturation measured by oxygen saturation to fraction of inspired oxygen ratio (SF)	From Study Days 1 to 7
Average preductal oxygen saturation measured by oxygen saturation index (OSI)	From Study Days 1 to 7
Incidence of grade 2 or grade 3 Bronchopulmonary Dysplasia (BPD) or death	Week 40 Post Menstrual Age (PMA)	BPD is defined and graded based on the classification according to Jensen et al., 2019 (2019 PMID: 30995069)
Incidence of grade 2 or grade 3 Bronchopulmonary Dysplasia (BPD) or death after excluding subjects with death at ≤ 14 days postnatal age	Week 36 and week 40 Post Menstrual Age (PMA)	BPD is defined and graded based on the classification according to Jensen et al., 2019 (2019 PMID: 30995069)
Survival at 6, 12 and 24 months corrected age	6, 12 and 24 month corrected age
Average number of hospitalizations and days in hospital	6 and 12 months corrected age
Incidence of chronic respiratory morbidity	12 month corrected age
Incidence of neurodevelopmental disability among survivors	24 months corrected age
Severity and frequency of treatment-emergent adverse events (TEAEs) or treatment-emergent serious adverse events (TESAEs)	From start of treatment through week 36 Post Menstrual Age (PMA) or hospital discharge, whichever comes first
Immunogenicity analysis	Day 28 of life	Determination of anti-SP-D antibodies in blood at day 28 of life compared to baseline), assessed in a subset of 60 patients

Trial Locations

Locations (18)

Bnai Zion Medical Center; 🇮🇱 Haifa, Israel

Shaare-Zedek Medical Center; 🇮🇱 Jerusalem, Israel

Ziv Medical Center; 🇮🇱 Safed, Israel

IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola; 🇮🇹 Bologna, Italy

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico; 🇮🇹 Milan, Italy

Ospedale dei Bambini "V. Buzzi"; 🇮🇹 Milan, Italy

Azienda Ospedale Università di Padova; 🇮🇹 Padua, Italy

Hospital General Universitario de Alicante Dr. Balmis; 🇪🇸 Alicante, Spain

Hospital de la Santa Creu i Sant Pau; 🇪🇸 Barcelona, Spain

Hospital Universitario Cruces - OSI Ezkerraldea-Enkarterri-Cruces; 🇪🇸 Bilbao, Spain

Scroll for more (8 remaining)