Bronchopulmonary Dysplasia
Conditions
Keywords
BPD, Zelpultide alfa, AT-100
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.
Interventions
OTHERAir-sham
Room air for intratracheal administration
DRUGZelpultide alfa
Reconstituted Zelpultide alfa for intratracheal administration
Sponsors
Airway Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
0 Years to 96 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Incidence of chronic respiratory morbidity | 12 month corrected age | — |
| Incidence of neurodevelopmental disability among survivors | 24 months corrected age | — |
| 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 | — |
| Ventilator-free days | From birth to 36 weeks 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 36 Post Menstrual Age (PMA) | — |
| 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 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 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) |
| 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 | — |
| Average number of hospitalizations and days in hospital | 6 and 12 months corrected age | — |
| 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 |
Countries
Israel, Italy, Spain
Contacts
CONTACTAlan Wolk
Outcome results
None listed