The Safety and Efficacy of Lucinactant for Inhalation in Premature Neonates 26 to 32 Weeks Gestational Age

A Multinational, Multicenter, Masked, Randomized, Controlled Study to Assess The Safety and Efficacy of Lucinactant for Inhalation in Preterm Neonates 26 to 32 Weeks Gestational Age With Respiratory Distress Syndrome

The primary objective of this study is to evaluate the safety and efficacy of lucinactant for inhalation administered as an aerosolized dose in two doses to preterm neonates 26 - 32 weeks gestational age who are receiving nasal continuous positive airway pressure (nCPAP) for Respiratory Distress Syndrome (RDS) compared to neonates receiving nCPAP alone.

Study Overview

• Status: Completed
• Conditions: Respiratory Distress Syndrome
• Intervention / Treatment: Drug: Lucinactant delivered via investigational delivery device; Drug: nCPAP

Detailed Description

The purpose of this study is to investigate the safety and efficacy of lucinactant for inhalation in preterm neonates 26 to 32 completed weeks post-menstrual age (PMA). Efficacy and safety are based on clinical evaluations. The endpoints specified are similar to those in Protocols 03-CL-1201 and 03-CL-1401 to allow for potential comparison and pooling of results.

The objective of this study is to evaluate the safety and efficacy of lucinactant for inhalation in conjunction with nCPAP, compared to nCPAP alone, in preterm neonates with RDS, as assessed by the time to and incidence of respiratory failure and/or death due to RDS over the first 72 hours of life, the incidence of bronchopulmonary dysplasia (BPD) at 36 weeks PMA, and change in physiologic parameters (FiO2 and PCO2) over the first 72 hours of life.

• Study Type: Interventional
• Enrollment (Actual): 221
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Foothills Medical Centre
    • Edmonton, Alberta, Canada, T5H 3V9
      • Royal Alexandra Hospital
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
  • Quebec
    • Montreal, Quebec, Canada, H3H 1P3
      • Montreal Children's Hospital
    • Montreal, Quebec, Canada, H3T 1C5
      • Sainte Justine Hospital
• Chile
  • Concepción, Chile, 4070038
    • Hospital Clínico Regional de Concepción Dr Guillermo Grant Benavente
  • Santiago, Chile, 8350488
    • Hospital San Juan de Dios
  • Santiago, Chile, 3330
    • Hospital San José
  • Santiago, Chile, 7650568
    • Clinica Alamena de Santiago
  • Santiago, Chile, 7980378
    • Hospital Santiago Oriente Dr Luis Tisné Brousse
  • Santiago, Chile, 8330024
    • Hospital Clinico de la Pontificia Universidad Catolica de Chile
  • Region-MetropolitanadeSantiago
    • Santiago, Region-MetropolitanadeSantiago, Chile, 8207257
      • Hospital Dr Sotero del Rio
• Colombia
  • Antioquia
    • Medellin, Antioquia, Colombia, 050010
      • Fundación Hospitalaria San Vicente de Paul
    • Medellin, Antioquia, Colombia, 050015
      • Hospital General de Medellin
  • Valle Del Cauca
    • Cali, Valle Del Cauca, Colombia, 760032
      • Fundación Valle del Lili
• Hungary
  • Budapest, Hungary, 1082
    • Semmelweis Egyetem
  • Debrecen, Hungary, 4032
    • Csolnoky Ferenc Korhaz
  • Debrecen, Hungary, H-4012
    • Debreceni Egyetem Klinikai Kozpont
  • Miskolc, Hungary, 3526
    • Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Okato
  • Nyiregyhaza, Hungary, H-4400
    • Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókórház
• Ireland
  • Cork, Ireland, T12 YN60
    • Cork University Hospital
  • Limerick, Ireland
    • Mid-Western Regional Hospital Limerick
• Netherlands
  • Rotterdam, Netherlands, 3000 CB
    • Erasmus Medical Center
• Poland
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland, 50-556
      • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
  • Kujawsko-pomorksie
    • Bydgoszcz, Kujawsko-pomorksie, Poland, 85-168
      • S.U. nr2im. Dr. Jana Biziela Oddzial Kliniczny N. W. Z. Intensywna Terapia Noworodka wraz z Wgjazdowy m Zespolem N
  • Lodzkie
    • Lodz, Lodzkie, Poland, 93-338
      • Instytut Centrum Zdrowja Matki Polki Klinika Neonatologii
  • Malopolskie
    • Krakow, Malopolskie, Poland, 31-501
      • SP ZOZ Szpital Uniwersytecki w Krakowie, Oddzial Neonatologii
  • Mazowieckie
    • Warsaw, Mazowieckie, Poland, 00-315
      • Szpital Kliniczny im. Ks, Anny Mazowieckiej Klinika Neonatologii
  • Pomorskie
    • Gdansk, Pomorskie, Poland, 80-402
      • Uniwersyteckie Centrum Kliniczne
  • Slaskie
    • Bytom, Slaskie, Poland, 41-902
      • Szpital Spegialistycszny nr 2 w Bytomia Oddzial Noworodkow Blok V
  • West Pomerania
    • Szczecin, West Pomerania, Poland, 70-780
      • Samodzielny Publiczny Specjalistczny Zaklad Opieki Zdrowotnej Zdroje
  • Wielkopolskie
    • Poznan, Wielkopolskie, Poland, 60-535
      • Ginekologiczno-Polozniczy Szpital Klinicznym UM im. Karola Marcinkowskiego w Poznan i u Katedra Neonatologii
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • University of Alabama at Birmingham
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Univ. of Arkansas Medical Center
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University Medical Center
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
    • San Diego, California, United States, 92123
      • Sharp Mary Birch Hospital for Women and Newborns
  • Delaware
    • Newark, Delaware, United States, 19713
      • Christiana Care Health System
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Holtz Children's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Nebraska
    • Omaha, Nebraska, United States, 68105
      • University of Nebraska Medical Center
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical Center
    • New York, New York, United States, 10032
      • Morgan Stanley Childrens Hospital of New York Presbyterian (CHONY)
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Greenville, North Carolina, United States, 27834
      • Brody School of Medicine at ECU
    • Wilmington, North Carolina, United States, 28401
      • New Hanover Regional Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University (Rainbow Babies Hosp.)
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Oregon
    • Portland, Oregon, United States, 97225
      • Providence St. Vincent Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women and Infants Hospital
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
    • Fort Worth, Texas, United States, 76104
      • Texas Health Harris Methodist Hospital
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 7 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed informed consent form (ICF) from legally authorized representative
2. 26 0/7 to 32 6/7 completed weeks gestation PMA
3. Successful implementation of non-invasive support or ventilation within 90 minutes after birth
4. Spontaneous breathing
5. Chest radiograph consistent with RDS
6. Within the first 20 hours after birth requires an nCPAP of 5 to 7 centimeters water (cmH2O) with a fraction of inspired oxygen (FiO2) of ≥ 0.25 (>0.21 for neonates 26-28 weeks PMA) to 0.40 that is clinically indicated for at least 30 minutes to maintain oxygen by pulse oximetry (SpO2) of 90% to 95%. Transient (<10 minutes) FiO2 excursions outside this range do not reset the 30-minute requirement.

Exclusion Criteria:

1. A heart rate that cannot be stabilized above 100 beats per minute (bpm) within 5 minutes of birth
2. Recurrent episodes of apnea requiring positive pressure ventilation (PPV) administered manually or mechanically through any patient interface
3. A 5 minute Apgar score < 5
4. Major congenital malformation(s) or craniofacial abnormalities that preclude the use of nCPAP, diagnosed antenatally or immediately after birth
5. Clinically significant diseases or conditions other than RDS which could potentially interfere with cardiopulmonary function (e.g. congenital heart disease, hydrops fetalis or congenital infection)
6. A known or suspected chromosomal abnormality or syndrome
7. Premature rupture of membranes (PROM) > 3 weeks
8. Hemodynamic instability requiring vasopressors or steroids for hemodynamic support and/or presumed clinical sepsis
9. A need for intubation and/or mechanical ventilation at any time before enrollment into the study

10. The administration (or plan for administration) of any the following:

    • Another investigational agent or investigational medical device
    • Any other surfactant agent
    • Systemic corticosteroids (other than antenatal steroids already received)
11. Presence of air leak (pneumothorax, pneumomediastinum, pneumopericardium, subcutaneous emphysema, or definite evidence of pulmonary interstitial emphysema (PIE)) on the baseline chest radiograph

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aerosolized lucinactant (low dose); Lucinactant for inhalation with nCPAP; up to 2 repeat doses will be allowed if repeat dosing criteria are met.	Drug: Lucinactant delivered via investigational delivery device; Lucinactant for inhalation refers to the active investigational agent lucinactant in combination with the investigational delivery device (drug-device combination product); Other Names: AEROSURF; Drug: nCPAP; Nasal CPAP
Experimental: Aerosolized lucinactant (high dose); Lucinactant for inhalation with nCPAP; up to 2 repeat doses will be allowed if repeat dosing criteria are met.	Drug: Lucinactant delivered via investigational delivery device; Lucinactant for inhalation refers to the active investigational agent lucinactant in combination with the investigational delivery device (drug-device combination product); Other Names: AEROSURF; Drug: nCPAP; Nasal CPAP
Active Comparator: nasal CPAP; nCPAP alone	Drug: nCPAP; Nasal CPAP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Respiratory Failure or Death Due to Respiratory Distress Syndrome (RDS)	Number of participants who had respiratory failure due to RDS or death due to RDS; known as nasal continuous positive airway pressure (nCPAP) failure	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Respiratory Failure or Death Due to RDS	Incidence of Respiratory Failure or Death Due to RDS by Intubation or Failure Criteria	72 hours
Time to nCPAP Failure	Time from birth to nCPAP Failure	72 hours
Incidence of Respiratory Failure or Death Due to RDS With Poisson Distribution Modeling	The measure tests the differences between treatments on respiratory failure or death due to RDS using Poisson distribution modeling, which accounts for the time over which the event could have occurred.	72 hours
Incidence of Respiratory Failure or Death Due to RDS	Incidence of Respiratory Failure or Death due to RDS by Intubation or Failure Criteria	28 days
Number of Participants With Bronchopulmonary Dysplasia (BPD)	Summarizes the number of participants with BPD or alive without BPD	36 weeks post-menstrual age (PMA)

Collaborators and Investigators

• Sponsor: Windtree Therapeutics
• Investigators: Study Director: Steven Simonson, MD, Windtree Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2015
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): August 6, 2019

Study Registration Dates

• First Submitted: November 19, 2015
• First Submitted That Met QC Criteria: December 17, 2015
• First Posted (Estimate): December 22, 2015

Study Record Updates

• Last Update Posted (Actual): April 23, 2021
• Last Update Submitted That Met QC Criteria: March 30, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Infant, Premature, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn
• Other Study ID Numbers: 03-CL-1202