A Clinical Safety Study of AT-100 (rhSP-D) in Preterm Neonates at High Risk for Bronchopulmonary Dysplasia (BPD)

Study Overview
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Brief Summary
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The purpose of this study is to determine if an investigational drug, AT-100, can reduce the occurrence of Bronchopulmonary Dysplasia (BPD) in babies born premature, as compared to babies born premature who receive an air-sham alone.

Official Title
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A Phase 1b, Randomized, Blinded, Dose-Determined Study Evaluating the Safety and Tolerability Profile of Intervention With AT-100 (rhSP-D) in Preterm Neonates at High Risk for the Development of Bronchopulmonary Dysplasia (BPD)

Conditions
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Bronchopulmonary Dysplasia

Intervention / Treatment
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* Biological: AT-100
* Procedure: Air-sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Preterm neonates born between Gestional Age (GA): 25 0/7 weeks to 28 6/7 weeks in the initial dose escalation cohorts. 23 0/7 weeks to 28 6/7 weeks in the latter cohort. Intubated and on mechanical ventilation. Receiving at least 1 dose of standard-of-care-indicated surfactant treatment (Curosurf®) after birth, and able to receive the first dose of AT-100 or air-sham within 96 hours of birth given at any time point after 15 minutes following any of the subject's Curosurf® dose(s). Parent or legal guardian is able to provide informed consent. Exclusion Criteria: Weight at time of birth < 400 g or > 1,800 g. Major apparent congenital abnormalities impacting cardio and pulmonary function. Active DNR (Do Not Resuscitate) order in place. Known pulmonary air leaks (e.g. pneumothorax and pneumomediastinum) at the time of AT-100 or air-sham administration. History of allergy or sensitivity to any surfactant or any component of the Investigational Product (AT-100). AT-100 or air-sham dosing was set to occur before Data Safety Monitoring Committee recommendation to proceed to the next dose-escalation cohort. Use of minimally invasive surfactant techniques (e.g., LISA, MIST) or INSURE or if, in the opinion of the care team, the infant is very likely too be extubated shortly after receiving Curosurf®. a. Subjects extubated and re-intubated after their Curosurf® dose(s) are eligible, so long as the subject meets Inclusion #3. Birth mother: Has known active Hepatitis B, C, or E diagnosis. Has a known illness or exposure that, in the judgement of the Investigator, is serious enough to induce an immune deficiency such as Human Immunodeficiency Virus (HIV) and/or is receiving chemotherapy. Has known active Sexually Transmitted Infection (STI). Has known Cytomegalovirus (CMV) active infection. Has known history or evidence of alcohol or drug abuse, wit the exception of marijuana/marijuana-based products/THC, based on a positive maternal or infant drug screen as evidenced by the institution's standard-of-care practice. Concurrent enrollment in an investigational drug, device, or treatment modulation trial that utilizes treatments outside of standard-of-care. Any condition or situation which, in the Investigator's judgement, puts the mother or the neonate at significant risk, could confound the trial results, or may interfere significantly with the mother's or neonate's participation in the trial. Symptomatic and confirmed COVID-19 infection of the mother around the time of birth.

Ages Eligible for Study
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Minimum Age: 0 Minutes
Maximum Age: 96 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Phase 1b portion is a randomized, dual-armed, dose escalation study to establish the safest & most tolerated AT-100 dose tested as compared to air-sham alone.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1b open-label AT-100<br>Once daily AT-100 via intratracheal administration for up to 2 doses (initial Phase 1b dose-escalation portion) or 7 doses (latter Phase 1b highest tolerated & safety dose level tested portion). | Biological: AT-100<br>* reconstituted AT-100 for intratracheal administration<br>* Other names: (rhSP-D);|
| Sham Comparator: Phase 1b open-label air-sham<br>Once daily air-sham via intratracheal administration for up to 2 doses (initial Phase 1b dose-escalation portion) or 7 doses (latter Phase 1b highest tolerated & safety dose level tested portion). | Procedure: Air-sham<br>* room air for intratracheal administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events | Incidence and severity of adverse events between the two treatment groups will be compared | Adverse events will be followed up to Day 28 of life | 
| Incidence of BPD or death |  | Week 36 PMA | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bronchopulmonary Dysplasia, Preterm, Neonate, Mechanical ventilation, Respiratory support, recombinant human Surfactant Protein-D (rhSP-D), intratracheal, air-sham