ZELA trial: Phase 2b/3 Multicenter Study to Evaluate the Efficacy and Safety of Zelpultide Alfa in Preterm Neonates at High Risk of Developing Bronchopulmonary Dysplasia (BPD) compared to standard of care (SOC)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Airway Therapeutics Inc., Airway Therapeutics Spain S.L.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

9 Jan 2025 → ongoing

Decision date (initial)

2026-02-04

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

Part 1 (Phase 2b / Dose Selection):
To explore the efficacy and safety of zelpultide alfa at two dose levels (4 mg/kg and 6 mg/kg) added to standard of care (SOC) compared to placebo (air-sham) added to SOC, in preterm neonates at high risk of developing BPD, to support dose selection for Part 2 (Phase 3).

Part 2 (Phase 3 / Confirmatory Phase):
To compare and confirm the efficacy of zelpultide alfa (at the selected dose) added to SOC versus placebo (air-sham) added to SOC in terms of incidence of grade 2 and grade 3 BPD and death in neonates at high risk for developing BPD.

Secondary objectives 4

1. Part 1 (Phase 2b / Dose Selection): To descriptively explore the effect of zelpultide alfa at 4 mg/kg and 6 mg/kg added to SOC compared to placebo (air-sham) added to SOC on the incidence of BPD and death in neonates at high risk for developing BPD.
2. Part 2 (Phase 3 / Confirmatory Phase): To confirm the efficacy of the selected zelpultide alfa dose added to SOC versus placebo (air-sham) added to SOC on secondary clinical outcomes in neonates at high risk for developing BPD.
3. To compare the incidence of respiratory comorbidities associated with prematurity and late neurodevelopmental outcome between zelpultide alfa (selected dose) added to SOC versus placebo (air-sham) added to SOC groups.
4. To compare the medical resource utilization and other health economic parameters between zelpultide alfa (selected dose) added to SOC versus placebo (air-sham) added to SOC in neonates at high risk for developing BPD

Conditions and MedDRA coding

prematurity in neonates

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-000023-PIP25-14

Plan to share IPD

No

IPD plan description

NA

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

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 birt
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 6

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 hernia, • Omphalocele or diaphragmaticgastroschisis, 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Part 1 (Phase 2b / Dose Selection): Incidence of grade 2 or grade 3 BPD or death at week 36 PMA, analyzed descriptively and used for the pre-specified futility assessment.
2. Part 2 (Phase 3 / Confirmatory Phase): Incidence of grade 2 or grade 3 BPD or death at week 36 PMA.

Secondary endpoints 3

1. Part 1 (Phase 2b / Dose Selection): Key Secondary Endpoints: Ventilator-free days from birth to week 36 PMA; Incidence of grade 2 or grade 3 BPD or death assessed at 3 consecutive days at week 36 PMA
2. Additional Efficacy Secondary Endpoints: Incidence of grade 2 or grade 3 BPD at week 36 PMA; Incidence of death at week 36 PMA; The proportion of subjects with no BPD, grade 1, grade 2, or grade 3 BPD at week 36 PMA; The proportion of subjects with no BPD, grade 1, grade 2, or grade 3 BPD assessed at 3 consecutive days at week 36 PMA.
3. Part 2 (Phase 3 / Confirmatory Phase): Key Efficacy Secondary Endpoints: Ventilator-free days from birth to week 36 PMA; Incidence of grade 2 or grade 3 BPD at week 36 PMA; Incidence of death at week 36 PMA; Incidence of grade 2 or grade 3 BPD or death assessed at 3 consecutive days at week 36 PMA.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Airway Therapeutics Inc.

Sponsor organisation

Airway Therapeutics Inc.

Address

1200 Johnson Ferry Road Suite 300

City

Marietta

Postcode

30068-5410

Country

United States

Scientific contact point

Organisation

Airway Therapeutics Inc.

Contact name

Senior Director, Quality Assurance, Quality Control, and Regulatory Affairs

Public contact point

Organisation

Airway Therapeutics Inc.

Contact name

Senior Director, Quality Assurance, Quality Control, and Regulatory Affairs

Third parties 3

Airway Therapeutics Spain S.L.

Sponsor organisation

Airway Therapeutics Spain S.L.

Address

Calle Principe De Vergara 112

City

Madrid

Postcode

28006

Country

Spain

Sponsor responsibilities

Article 77 compliance

Airway Therapeutics Inc.

Contact point sponsor

Airway Therapeutics Inc.

Article 77 implementation

Airway Therapeutics Inc.

Locations

6 EU/EEA countries · 47 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 2 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 28 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

15 submissions — initial application plus substantial / non-substantial modifications