A Safety and Efficacy Study of Lucinactant for Inhalation in Preterm Neonates 26 to 32 Weeks GA

• ClinicalTrials.gov Identifier: NCT04264156
• Recruitment Status: Suspended
• First Posted: February 11, 2020
• Last Update Posted: January 14, 2021
• Sponsor: Windtree Therapeutics
• Information provided by (Responsible Party): Windtree Therapeutics

Study Description

Brief Summary:

This study is to evaluate the safety and efficacy of lucinactant for inhalation in conjunction with nCPAP, in comparison to nCPAP alone, in preterm neonates with RDS, as assessed by the incidence of and time to respiratory failure and/or death due to RDS in the first 72 hours and 28 days of life. Half of the subjects will receive lucinactant for inhalation and half will receive standard of care (nCPAP alone).

Condition or disease	Intervention/treatment	Phase
Respiratory Distress Syndrome, Newborn	Combination Product: Lucinactant for Inhalation; Other: nCPAP Only	Phase 2

Detailed Description:

An unmet medical need exists for a means to deliver SRT to preterm neonates with RDS supported with nCPAP early in the course of the disease. This strategy has the potential to improve RDS prior to the development of respiratory failure, thereby avoiding the need for endotracheal intubation and MV, or reduce the duration of MV, and the resultant potential for morbidity and complications. The ability to administer SRT via aerosol has the potential to address this unmet need.

Lucinactant for inhalation (AEROSURF) is an investigational drug-device combination product, designed to deliver aerosolized SRT to preterm neonates with RDS who are being supported with nCPAP. The drug component of lucinactant for inhalation is lyophilized lucinactant, a lyophilized form of SURFAXIN® (lucinactant) Intratracheal Suspension. The device component, the AEROSURF Delivery System (ADS), the next-generation device following use of the prototype device in earlier trials, uses novel technology to aerosolize lucinactant for inhalation.

This study evaluates the safety and efficacy of lucinactant for inhalation in conjunction with nCPAP, in comparison to nCPAP alone, in preterm neonates with RDS, as assessed by pre-specified outcome measures. In addition, this study will evaluate the device and the ability to administer up to 3 repeat doses.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This study is a multinational, multicenter, double-blind (masked), parallel group, randomized, controlled study, in preterm neonates 26 to 32 completed weeks PMA.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: The first 2 subjects at each site will be dosed with open-label active treatment. Following the first 2 subjects, preparation and delivery of treatment will be blinded from the study staff. Treatment will be delivered behind a partition and no information about treatment will be given to investigator, outcomes assessor, parents, or other applicable study staff.
• Primary Purpose: Treatment
• Official Title: A Multinational, Multicenter, Masked, Randomized, Controlled Study to Assess the Safety and Efficacy of Lucinactant for Inhalation Versus nCPAP Alone in Preterm Neonates 26 to 32 Weeks Gestational Age With RDS
• Actual Study Start Date: April 18, 2020
• Estimated Primary Completion Date: January 31, 2021
• Estimated Study Completion Date: February 28, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: 160 mg/kg; Lucinactant for inhalation, 160 mg total phospholipids (TPL)/kg Delivered as an aerosol once, with up to 3 repeats of 80 mg/kg allowed within 36 hours of birth	Combination Product: Lucinactant for Inhalation; A drug-device combination product that delivers aerosolized SRT to preterm neonates with RDS who are being supported with nCPAP.; Other Name: AEROSURF
Sham Comparator: nCPAP Only; nCPAP Only as sham comparator. Bubble nCPAP is standard of care. Treatment time behind barrier to match active treatment delivery time	Other: nCPAP Only; Nasal CPAP Alone

Outcome Measures

Primary Outcome Measures :

1. Number of Participants with Respiratory Failure or Death [ Time Frame: 28 days of life ]
   Number of participants with respiratory failure due to RDS or death. Respiratory failure due to RDS is defined as intubation for mechanical ventilation and/or surfactant administration

Secondary Outcome Measures :

1. Number of Participants with Respiratory Failure due to RDS [ Time Frame: 72 hours and 28 days of life ]
   Number of participants with respiratory failure due to RDS. Respiratory failure due to RDS is defined as intubation for mechanical ventilation and/or surfactant administration
2. Time to respiratory failure due to RDS [ Time Frame: 72 hours and 28 days of life ]
   Time at which intubation for mechanical ventilation and/or surfactant administration occurred
3. Number of participants with bronchopulmonary dysplasia [ Time Frame: 36 weeks PMA ]
   Number of participants with bronchopulmonary dysplasia
4. Number of participants alive and without evidence of BPD [ Time Frame: 36 weeks PMA ]
5. All-cause mortality [ Time Frame: 36 weeks PMA or 28 days of life (whichever is later) ]
   All-cause mortality
6. Number of Participants with Common Complications of Prematurity [ Time Frame: 36 weeks PMA ]
   Number of participants with complications including intraventricular hemorrhage, periventricular leukomalacia, pulmonary hemorrhage, apnea, necrotizing enterocolitis, patent ductus arteriosus, acquired sepsis, and retinopathy of prematurity.
7. Length of time subjects received mechanical ventilation and/or supplemental oxygen [ Time Frame: Through 36 weeks PMA ]
8. Changes in PCO2 gas exchange [ Time Frame: Through 7 days of life ]
   Changes in PCO2 (through 72 hours only)
9. Changes in gas exchange [ Time Frame: Through 7 days of life ]
   Changes in FiO2 (as determined by pulse oximetry)
10. Re-hospitalizations post discharge [ Time Frame: Through 12 months corrected age ]
    Number of participants with, duration of, and reason for re-hospitalizations following initial discharge

Eligibility Criteria

• Ages Eligible for Study: up to 6 Hours (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Signed ICF from legally authorized representative.
• Gestational age: 26 to 32+6 weeks PMA.
• Successful implementation of non-invasive support or ventilation within 30 minutes after birth.
• Spontaneous breathing.
• Investigator determination of RDS. A chest x-ray should be obtained before treatment to confirm the diagnosis.
• Within the first 6 hours after birth, requires an nCPAP of 5 to 7 cm H2O that is clinically indicated for at least 15 minutes with an FiO2 > 0.25 to ≤ 0.35 to maintain SpO2 of 90% to 95%.

Exclusion Criteria:

• A heart rate that cannot be stabilized above 100 bpm within 5 minutes of birth.
• Recurrent episodes of apnea requiring positive pressure ventilation.
• A 5 minute Apgar score < 5.
• Major congenital malformation(s) or craniofacial abnormalities that preclude the use of nCPAP.
• Clinically significant diseases or conditions other than RDS which could potentially interfere with cardiopulmonary function.
• A known or suspected chromosomal abnormality or syndrome.
• Premature rupture of membranes > 3 weeks.
• Hemodynamic instability requiring vasopressors or steroids for hemodynamic support and/or presumed clinical sepsis.
• A need for intubation and/or invasive mechanical ventilation at any time before enrollment into the study.
• The administration (or plan for administration) of another investigational agent or investigational medical device, any other surfactant agent, or systemic corticosteroids.
• Presence of air leak on the baseline chest radiograph or diagnosed via ultrasound or illumination.

Contacts and Locations

Locations

Poland

Szpital Specjalistyczny nr 2 w Bytomiu Oddzial Noworodkow Blok Va

Bytom, Poland, 41-902

Ginekologiczno-Polozniczy Szpital Kliniczny Uniwewersytetu Medycznego im. Karola Marcinkowskiego

Poznan, Poland, 60-535

Samodzielny Publiczny Spcjalistyczny Zaklad Opieki Zdrowotnej "Zdroje", Oddzial Noworodkow

Szczecin, Poland, 70-780

Sponsors and Collaborators

Windtree Therapeutics

Investigators

• Principal Investigator: Carlos Guardia, MD; Windtree Therapeutics, Inc.

More Information

• Responsible Party: Windtree Therapeutics
• ClinicalTrials.gov Identifier: NCT04264156
• Other Study ID Numbers: 03-CL-1702
• First Posted: February 11, 2020
• Last Update Posted: January 14, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Keywords provided by Windtree Therapeutics:

intubation; surfactant; continuous positive airway pressure; aerosol; respiratory distress syndrome

Additional relevant MeSH terms:

Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases