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

Phase 2

Completed

• Conditions: Respiratory Distress Syndrome
• Interventions: Drug: Lucinactant delivered via investigational delivery device; Drug: nCPAP

• Registration Number: NCT02636868
• Lead Sponsor: Windtree Therapeutics

Brief Summary

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.

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 Timeline

• Study First Submitted: 2015-11-19
• Study Start: 2015-12
• Study First Submitted QC: 2015-12-17
• Study First Posted: 2015-12-22
• Primary Completion: 2017-07
• Study Completion: 2019-08-06
• Results First Submitted: 2021-02-05
• Status Verified: 2021-03
• Results First Submitted QC: 2021-03-30
• Last Update Submitted: 2021-03-30
• Results First Posted: 2021-04-23
• Last Update Posted: 2021-04-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 221

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Aerosolized lucinactant (low dose)	Lucinactant delivered via investigational delivery device	Lucinactant for inhalation with nCPAP; up to 2 repeat doses will be allowed if repeat dosing criteria are met.
Aerosolized lucinactant (low dose)	nCPAP	Lucinactant for inhalation with nCPAP; up to 2 repeat doses will be allowed if repeat dosing criteria are met.
Aerosolized lucinactant (high dose)	Lucinactant delivered via investigational delivery device	Lucinactant for inhalation with nCPAP; up to 2 repeat doses will be allowed if repeat dosing criteria are met.
Aerosolized lucinactant (high dose)	nCPAP	Lucinactant for inhalation with nCPAP; up to 2 repeat doses will be allowed if repeat dosing criteria are met.
nasal CPAP	nCPAP	nCPAP alone

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Incidence of Respiratory Failure or Death Due to RDS	28 days	Incidence of Respiratory Failure or Death due to RDS by Intubation or Failure Criteria
Time to nCPAP Failure	72 hours	Time from birth to nCPAP Failure
Incidence of Respiratory Failure or Death Due to RDS With Poisson Distribution Modeling	72 hours	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.
Number of Participants With Bronchopulmonary Dysplasia (BPD)	36 weeks post-menstrual age (PMA)	Summarizes the number of participants with BPD or alive without BPD

Trial Locations

Locations (54)

Baylor University Medical Center; 🇺🇸 Dallas, Texas, United States

Univ. of Arkansas Medical Center; 🇺🇸 Little Rock, Arkansas, United States

Case Western Reserve University (Rainbow Babies Hosp.); 🇺🇸 Cleveland, Ohio, United States

Loma Linda University Medical Center; 🇺🇸 Loma Linda, California, United States

Children's Hospital of Orange County; 🇺🇸 Orange, California, United States

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Hospital Clínico Regional de Concepción Dr Guillermo Grant Benavente; 🇨🇱 Concepción, Chile

Sharp Mary Birch Hospital for Women and Newborns; 🇺🇸 San Diego, California, United States

University of Miami Holtz Children's Hospital; 🇺🇸 Miami, Florida, United States

Cork University Hospital; 🇮🇪 Cork, Ireland

SP ZOZ Szpital Uniwersytecki w Krakowie, Oddzial Neonatologii; 🇵🇱 Krakow, Malopolskie, Poland

Szpital Spegialistycszny nr 2 w Bytomia Oddzial Noworodkow Blok V; 🇵🇱 Bytom, Slaskie, Poland

Fundacion Valle Del Lili; 🇨🇴 Cali, Valle Del Cauca, Colombia

University of Mississippi Medical Center; 🇺🇸 Jackson, Mississippi, United States

Hospital General de Medellin; 🇨🇴 Medellin, Antioquia, Colombia

Uniwersyteckie Centrum Kliniczne; 🇵🇱 Gdansk, Pomorskie, Poland

Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Okato; 🇭🇺 Miskolc, Hungary

Szpital Kliniczny im. Ks, Anny Mazowieckiej Klinika Neonatologii; 🇵🇱 Warsaw, Mazowieckie, Poland

Debreceni Egyetem Klinikai Kozpont; 🇭🇺 Debrecen, Hungary

S.U. nr2im. Dr. Jana Biziela Oddzial Kliniczny N. W. Z. Intensywna Terapia Noworodka wraz z Wgjazdowy m Zespolem N; 🇵🇱 Bydgoszcz, Kujawsko-pomorksie, Poland

Samodzielny Publiczny Specjalistczny Zaklad Opieki Zdrowotnej Zdroje; 🇵🇱 Szczecin, West Pomerania, Poland

Ginekologiczno-Polozniczy Szpital Klinicznym UM im. Karola Marcinkowskiego w Poznan i u Katedra Neonatologii; 🇵🇱 Poznan, Wielkopolskie, Poland

Christiana Care Health System; 🇺🇸 Newark, Delaware, United States

Albany Medical Center; 🇺🇸 Albany, New York, United States

University of Nebraska Medical Center; 🇺🇸 Omaha, Nebraska, United States

Morgan Stanley Childrens Hospital of New York Presbyterian (CHONY); 🇺🇸 New York, New York, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Ohio State University; 🇺🇸 Columbus, Ohio, United States

Brody School of Medicine at ECU; 🇺🇸 Greenville, North Carolina, United States

Providence St. Vincent Medical Center; 🇺🇸 Portland, Oregon, United States

Foothills Medical Centre; 🇨🇦 Calgary, Alberta, Canada

Women and Infants Hospital; 🇺🇸 Providence, Rhode Island, United States

Sainte Justine Hospital; 🇨🇦 Montreal, Quebec, Canada

Sunnybrook Health Sciences Centre; 🇨🇦 Toronto, Ontario, Canada

Cook Children's Hospital; 🇺🇸 Fort Worth, Texas, United States

Texas Health Harris Methodist Hospital; 🇺🇸 Fort Worth, Texas, United States

Montreal Children's Hospital; 🇨🇦 Montreal, Quebec, Canada

Hospital Dr Sotero Del Rio; 🇨🇱 Santiago, Region-MetropolitanadeSantiago, Chile

Hospital San Jose; 🇨🇱 Santiago, Chile

Clinica Alamena de Santiago; 🇨🇱 Santiago, Chile

Hospital Santiago Oriente Dr Luis Tisné Brousse; 🇨🇱 Santiago, Chile

Hospital San Juan de Dios; 🇨🇱 Santiago, Chile

Hospital Clinico de la Pontificia Universidad Catolica de Chile; 🇨🇱 Santiago, Chile

Fundacion Hospitalaria San Vicente de Paul; 🇨🇴 Medellin, Antioquia, Colombia

Semmelweis Egyetem; 🇭🇺 Budapest, Hungary

Csolnoky Ferenc Korhaz; 🇭🇺 Debrecen, Hungary

Mid-Western Regional Hospital Limerick; 🇮🇪 Limerick, Ireland

Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz; 🇭🇺 Nyiregyhaza, Hungary

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu; 🇵🇱 Wroclaw, Dolnoslaskie, Poland

Erasmus Medical Center; 🇳🇱 Rotterdam, Netherlands

Instytut Centrum Zdrowja Matki Polki Klinika Neonatologii; 🇵🇱 Lodz, Lodzkie, Poland

Royal Alexandra Hospital; 🇨🇦 Edmonton, Alberta, Canada

New Hanover Regional Medical Center; 🇺🇸 Wilmington, North Carolina, United States

University of Michigan Health System; 🇺🇸 Ann Arbor, Michigan, United States