Clinical trial NCT04662151: A Clinical Safety Study of AT-100 (rhSP-D) in Preterm Neonates at High Risk for Bronchopulmonary Dysplasia (BPD)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Bronchopulmonary Dysplasia
Keywords: Bronchopulmonary Dysplasia
Preterm
Neonate
Mechanical ventilation
Respiratory support
recombinant human Surfactant Protein-D (rhSP-D)
intratracheal
air-sham
Lead sponsor: Airway Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2020-12-10
Enrollment: 37
Sex: ALL
Minimum age (years): 0
Maximum age (years): 96
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: Inclusion Criteria

1. Preterm neonates born between Gestional Age (GA):

   1. 25 0/7 weeks to 28 6/7 weeks in the initial dose escalation cohorts.
   2. 23 0/7 weeks to 28 6/7 weeks in the latter cohort.
2. Intubated and on mechanical ventilation.
3. 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).
4. Parent or legal guardian is able to provide informed consent.

Exclusion Criteria:

1. Weight at time of birth \< 400 g or \> 1,800 g.
2. Major apparent congenital abnormalities impacting cardio and pulmonary function.
3. Active DNR (Do Not Resuscitate) order in place.
4. Known pulmonary air leaks (e.g. pneumothorax and pneumomediastinum) at the time of AT-100 or air-sham administration.
5. History of allergy or sensitivity to any surfactant or any component of the Investigational Product (AT-100).
6. AT-100 or air-sham dosing was set to occur before Data Safety Monitoring Committee recommendation to proceed to the next dose-escalation cohort.
7. 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.
8. Birth mother:

   1. Has known active Hepatitis B, C, or E diagnosis.
   2. 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.
   3. Has known active Sexually Transmitted Infection (STI).
   4. Has known Cytomegalovirus (CMV) active infection.
   5. 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.
9. Concurrent enrollment in an investigational drug, device, or treatment modulation trial that utilizes treatments outside of standard-of-care.
10. 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.
11. Symptomatic and confirmed COVID-19 infection of the mother around the time of birth.

Primary outcomes:
measure: Number of participants with treatment-related adverse events
timeFrame: Adverse events will be followed up to Day 28 of life
measure: Incidence of BPD or death
timeFrame: Week 36 PMA
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Airway Therapeutics Investigational Site
state: Arizona
city: Little Rock
country: United States
facility: Airway Therapeutics Investigational Site
state: Arkansas
city: Los Angeles
country: United States
facility: Airway Therapeutics Investigational Site
state: California
city: Miami
country: United States
facility: Airway Therapeutics Investigational Site
state: Florida
city: Atlanta
country: United States
facility: Airway Therapeutics Investigational Site
state: Georgia
city: Indianapolis
country: United States
facility: Airway Therapeutics Investigational Site
state: Indiana
city: Boston
country: United States
facility: Airway Therapeutics Investigational Site
state: Massachusetts
city: Durham
country: United States
facility: Airway Therapeutics Investigational Site
state: North Carolina
city: Norfolk
country: United States
facility: Airway Therapeutics Investigational Site
state: Virginia
city: Cadiz
country: Spain
facility: Airway Therapeutics Investigational Site
state: Andalucia
city: Barcelona
country: Spain
facility: Airway Therapeutics Investigational Site
state: Cataluña
city: Madrid
country: Spain
facility: Airway Therapeutics Investigational Site
state: Comunidad De Madrid
city: Madrid
country: Spain
facility: Airway Therapeutics Investigational Site
state: Comunidad De Madrid
city: Alicante
country: Spain
facility: Airway Therapeutics Investigational Site
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Airway Therapeutics Investigational Site
state: Comunidad Valenciana
city: Santiago De Compostela
country: Spain
facility: Airway Therapeutics Investigational Site
state: Galicia
city: A Coruña
country: Spain
facility: Airway Therapeutics Investigational Site
city: Lleida
country: Spain
facility: Airway Therapeutics Investigational Site
city: Málaga
country: Spain
facility: Airway Therapeutics Investigational Site
Study officials:
affiliation: Airway Therapeutics, Inc.
name: Marc O. Salzberg, MD
role: STUDY_CHAIR
References:
citation: Thebaud B, Goss KN, Laughon M, Whitsett JA, Abman SH, Steinhorn RH, Aschner JL, Davis PG, McGrath-Morrow SA, Soll RF, Jobe AH. Bronchopulmonary dysplasia. Nat Rev Dis Primers. 2019 Nov 14;5(1):78. doi: 10.1038/s41572-019-0127-7.
citation: Jensen EA, Dysart K, Gantz MG, McDonald S, Bamat NA, Keszler M, Kirpalani H, Laughon MM, Poindexter BB, Duncan AF, Yoder BA, Eichenwald EC, DeMauro SB. The Diagnosis of Bronchopulmonary Dysplasia in Very Preterm Infants. An Evidence-based Approach. Am J Respir Crit Care Med. 2019 Sep 15;200(6):751-759. doi: 10.1164/rccm.201812-2348OC.
citation: Sorensen GL. Surfactant Protein D in Respiratory and Non-Respiratory Diseases. Front Med (Lausanne). 2018 Feb 8;5:18. doi: 10.3389/fmed.2018.00018. eCollection 2018.
citation: Sato A, Whitsett JA, Scheule RK, Ikegami M. Surfactant protein-d inhibits lung inflammation caused by ventilation in premature newborn lambs. Am J Respir Crit Care Med. 2010 May 15;181(10):1098-105. doi: 10.1164/rccm.200912-1818OC. Epub 2010 Feb 4.
citation: Ikegami M, Carter K, Bishop K, Yadav A, Masterjohn E, Brondyk W, Scheule RK, Whitsett JA. Intratracheal recombinant surfactant protein d prevents endotoxin shock in the newborn preterm lamb. Am J Respir Crit Care Med. 2006 Jun 15;173(12):1342-7. doi: 10.1164/rccm.200509-1485OC. Epub 2006 Mar 23.