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

Randomized, Double-Blind Parallel-Group, Adaptive, Three-Arm, Phase 2b/3 Multicenter Study to Evaluate the Efficacy and Safety of Zelpultide Alfa in Preventing Bronchopulmonary Dysplasia (BPD) in High-Risk Preterm Neonates Compared to Standard of Care (SOC)

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 Overview

• Status: Recruiting
• Conditions: Bronchopulmonary Dysplasia
• Intervention / Treatment: Drug: Zelpultide alfa; Other: Air-sham

• Study Type: Interventional
• Enrollment (Estimated): 366
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Alan Wolk; Phone Number: 513-770-9630; Email: info@airwaytherapeutics.com

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Recruiting
    • Hospital Italiano de Buenos Aires
  • Buenos Aires, Argentina
    • Recruiting
    • Hospital Universitario Austral
  • Buenos Aires, Argentina
    • Recruiting
    • Clínica y Maternidad Suizo Argentina
  • Buenos Aires, Argentina
    • Not yet recruiting
    • Hospital Sanatorio de la Trinidad San Isidro
• Belgium
  • Antwerp, Belgium
    • Not yet recruiting
    • ZAS Middelheim
  • Brussels, Belgium
    • Not yet recruiting
    • Cliniques Universitaires Saint-luc
  • Leuven, Belgium
    • Not yet recruiting
    • UZ Leuven
  • Liège, Belgium
    • Recruiting
    • Clinique CHC MontLégia
  • Liège, Belgium
    • Not yet recruiting
    • CHU de Liege - Hospital de la Citadelle
• France
  • Lille, France
    • Recruiting
    • CHU Lille - Hôpital Jeanne de Flandre
  • Nancy, France
    • Recruiting
    • Chru Nancy
  • Nice, France
    • Not yet recruiting
    • CHU Nice
  • Paris, France
    • Recruiting
    • AP-HP Paris Saclay University - Hôpitaux Antoine-Béclère
  • Paris, France
    • Recruiting
    • AP-HP CHU Robert-Debré - Hôpitaux de Paris
  • Paris, France
    • Recruiting
    • AP-HP Paris Saclay University Bicêtre Hospital
  • Paris, France
    • Recruiting
    • AP-HP University Hospital Cochin - Port Royal
  • Poissy, France
    • Recruiting
    • Hôpital de Poissy Saint-Germain-en-Laye
• Germany
  • Dresden, Germany
    • Not yet recruiting
    • Medical Faculty of TU Dresden
  • Freiburg im Breisgau, Germany
    • Not yet recruiting
    • Universitatsklinikum Freiburg
  • Regensburg, Germany
    • Recruiting
    • University Children's Hospital Regensburg (KUNO)
• Israel
  • Haifa, Israel
    • Recruiting
    • Rambam Medical Center
  • Haifa, Israel
    • Not yet recruiting
    • Bnai Zion Medical Center
    • Contact: Ayala Gover
  • Jerusalem, Israel
    • Recruiting
    • Shaare-Zedek Medical Center
  • Jerusalem, Israel
    • Not yet recruiting
    • Haddasah medical center
  • Safed, Israel
    • Recruiting
    • Ziv Medical Center
• Italy
  • Bologna, Italy
    • Recruiting
    • IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola
  • Genova, Italy
    • Not yet recruiting
    • Istituto Giannina Gaslini
  • Milan, Italy
    • Recruiting
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
  • Milan, Italy
    • Recruiting
    • Ospedale dei Bambini "V. Buzzi"
  • Naples, Italy
    • Recruiting
    • Università Degli Studi Di Napoli Federico Ii
  • Padova, Italy
    • Recruiting
    • Azienda Ospedale Università di Padova
• Poland
  • Gdansk, Poland
    • Not yet recruiting
    • Uniwersyteckie Centrum Kliniczne
  • Krakow, Poland
    • Not yet recruiting
    • University Hospital in Krakow
  • Lodz, Poland
    • Not yet recruiting
    • Polish Mother's Memorial Hospital - Research Institute in Lodz
  • Poznan, Poland
    • Recruiting
    • Gynecological Obstetric Clinical Hospital of Poznan University of Medical Sciences
  • Szczecin, Poland
    • Not yet recruiting
    • University Clinical Hospital No. 2 PUM
  • Wroclaw, Poland
    • Recruiting
    • University Hospital Wroclaw
• Spain
  • Alicante, Spain
    • Recruiting
    • Hospital General Universitario de Alicante Dr. Balmis
    • Contact: Tapia Collados; Email: hgralalicante_saip@gva.es
  • Barcelona, Spain
    • Recruiting
    • Hospital Clinic de Barcelona
  • Barcelona, Spain
    • Recruiting
    • Hospital Sant Joan de Déu
  • Barcelona, Spain
    • Recruiting
    • Hospital de la Santa Creu i Sant Pau
    • Contact: Moliner Calderón; Phone Number: +3493 553 70 75; Email: pediatria@santpau.cat
  • Bilbao, Spain
    • Recruiting
    • Hospital Universitario Cruces - OSI Ezkerraldea-Enkarterri-Cruces
    • Contact: Ferrer Arriazu; Email: Secretaria1.sapucruces@osakidetza.eus
  • Cadiz, Spain
    • Recruiting
    • Hospital Universitario Puerta del Mar
    • Contact: Alonso Ojembarrena; Email: almudena.alonso.sspa@juntadeandalucia.es
  • Lleida, Spain
    • Recruiting
    • Hospital Universitari Arnau de Vilanova de Lleida
    • Contact: Solé Mir; Email: atencioalciutada.lleida.ics@gencat.cat
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario La Paz
    • Contact: Sánchez Torres; Email: asancheztorres@salud.madrid.org
  • Madrid, Spain
    • Not yet recruiting
    • Hospital General Universitario Gregorio Marañon
    • Contact: Sánchez Luna; Email: sap.hgugm@salud.madrid.org
  • Málaga, Spain
    • Recruiting
    • Hospital Regional Universitario de Malaga
    • Contact: Serrano Martín; Email: gestoria.hmi.hrmal.sspa@juntadeandalucia.es
  • Santiago de Compostela, Spain
    • Recruiting
    • Hospital Clínico Universitario de Santiago
    • Contact: Couce Pico; Email: Maria.Luz.Couce.Pico@sergas.es
  • Valencia, Spain
    • Recruiting
    • Hospital Universitari i Politecnic La Fe
    • Contact: Aguar Carrascosa; Email: prensa_lafe@gva.es
  • Zaragoza, Spain
    • Recruiting
    • Hospital Universitario Miguel Servet
    • Contact: Rite García; Email: informacion.sector2@salud.aragon.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Placebo (air-sham) plus standard of care; 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.	Other: Air-sham; Room air for intratracheal administration
Experimental: Zelpultide alfa 4 mg/kg plus standard of care; 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.	Drug: Zelpultide alfa; Reconstituted Zelpultide alfa for intratracheal administration; Other Names: AT-100; rhSP-D
Experimental: Zelpultide alfa 6 mg/kg plus standard of care; 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.	Drug: Zelpultide alfa; Reconstituted Zelpultide alfa for intratracheal administration; Other Names: AT-100; rhSP-D

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Week 36 Post Menstrual Age (PMA)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From birth to 36 weeks Post Menstrual Age (PMA)
Incidence of grade 2 or grade 3 Bronchopulmonary Dysplasia (BPD)		Week 36 Post Menstrual Age (PMA)
Incidence of death		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)	Week 36 Post Menstrual Age (PMA)
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.	From birth to day 28 of life
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 index (OSI)		From Study Days 1 to 7
Average preductal oxygen saturation measured by oxygen saturation to fraction of inspired oxygen ratio (SF)		From Study Days 1 to 7
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
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)	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)	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)	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)	Week 36 and week 40 Post Menstrual Age (PMA)
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.	From birth to week 40 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)	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)	Week 36 Post Menstrual Age (PMA)
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	Day 28 of life

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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)	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)	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)	Week 36 and week 40 Post Menstrual Age (PMA)
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.	From birth to week 40 Post Menstrual Age (PMA)

Collaborators and Investigators

• Sponsor: Airway Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2025
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): April 30, 2030

Study Registration Dates

• First Submitted: February 20, 2025
• First Submitted That Met QC Criteria: March 20, 2025
• First Posted (Actual): March 27, 2025

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: BPD; Zelpultide alfa; AT-100
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Lung Injury; Ventilator-Induced Lung Injury; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Bronchopulmonary Dysplasia
• Other Study ID Numbers: ZEL-003; 2024-513420-41-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes