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

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)

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.

Study Overview

• Status: Completed
• Conditions: Bronchopulmonary Dysplasia
• Intervention / Treatment: Biological: AT-100; Procedure: Air-sham

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • A Coruña, Spain, 15006
    • Airway Therapeutics Investigational Site
  • Lleida, Spain, 25198
    • Airway Therapeutics Investigational Site
  • Málaga, Spain, 29010
    • Airway Therapeutics Investigational Site
  • Andalucia
    • Cadiz, Andalucia, Spain, 11009
      • Airway Therapeutics Investigational Site
  • Cataluña
    • Barcelona, Cataluña, Spain, 08041
      • Airway Therapeutics Investigational Site
  • Comunidad De Madrid
    • Madrid, Comunidad De Madrid, Spain, 28007
      • Airway Therapeutics Investigational Site
    • Madrid, Comunidad De Madrid, Spain, 28046
      • Airway Therapeutics Investigational Site
  • Comunidad Valenciana
    • Alicante, Comunidad Valenciana, Spain, 03010
      • Airway Therapeutics Investigational Site
    • Valencia, Comunidad Valenciana, Spain, 46026
      • Airway Therapeutics Investigational Site
  • Galicia
    • Santiago De Compostela, Galicia, Spain, 15706
      • Airway Therapeutics Investigational Site
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Airway Therapeutics Investigational Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Airway Therapeutics Investigational Site
  • California
    • Los Angeles, California, United States, 90017
      • Airway Therapeutics Investigational Site
  • Florida
    • Miami, Florida, United States, 33143
      • Airway Therapeutics Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Airway Therapeutics Investigational Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Airway Therapeutics Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Airway Therapeutics Investigational Site
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Airway Therapeutics Investigational Site
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Airway Therapeutics Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 4 days (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1b open-label AT-100; 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; reconstituted AT-100 for intratracheal administration; Other Names: (rhSP-D)
Sham Comparator: Phase 1b open-label air-sham; 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; room air for intratracheal administration

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Airway Therapeutics, Inc.
• Investigators: Study Chair: Marc O. Salzberg, MD, Airway Therapeutics, Inc.

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Helpful Links

• Airway Therapeutics' corporate website

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Actual): August 14, 2023
• Study Completion (Actual): May 29, 2024

Study Registration Dates

• First Submitted: December 4, 2020
• First Submitted That Met QC Criteria: December 4, 2020
• First Posted (Actual): December 10, 2020

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: July 2, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Neonate; Mechanical ventilation; Preterm; Bronchopulmonary Dysplasia; recombinant human Surfactant Protein-D (rhSP-D); Respiratory support; intratracheal; air-sham
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Ventilator-Induced Lung Injury; Hyperplasia; Bronchopulmonary Dysplasia
• Other Study ID Numbers: AT-100/001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No