Trial To Assess The Safety And Tolerability Of Lucinactant For Inhalation In Preterm Neonates 26 to 28 Weeks PMA

A Multicenter, Randomized, Open-label, Controlled Trial To Assess The Safety And Tolerability Of Lucinactant For Inhalation In Preterm Neonates 26 to 28 Weeks PMA

This study is to evaluate the safety and tolerability of lucinactant for inhalation, administered as an aerosol in up to four escalating doses to preterm neonates 26 to 28 weeks gestational age who are receiving nCPAP for RDS compared to neonates receiving nCPAP alone.

Study Overview

• Status: Terminated
• Conditions: Respiratory Distress Syndrome
• Intervention / Treatment: Device: nCPAP alone; Combination product: Lucinactant for inhalation

Detailed Description

This study was a multicenter, randomized, controlled, open-label, dose-escalation study, conducted to evaluate the safety and tolerability of lucinactant for inhalation in conjunction with nasal continuous positive airway pressure (nCPAP) in comparison with nCPAP alone. The study was to evaluate the safety and tolerability of lucinactant for inhalation, administered as an aerosol in 4 escalating doses.

For this study, lucinactant for inhalation refers to the active investigational agent, lyophilized lucinactant, in combination with the prototype investigational delivery device. Reconstituted lyophilized lucinactant was aerosolized by the investigational device and introduced into the nCPAP circuit. Those randomized to the control arm continued to receive nCPAP alone. Dose assignments were unblinded, as the primary objective of this study was safety and tolerability.

Preterm neonates with respiratory distress syndrome (RDS) between 26 and 28 completed weeks PMA who were within the first 20 hours after birth and who had successful implementation of controlled nCPAP within 90 minutes of birth were considered to be potential subjects. Before study enrollment, legal guardians were provided a written informed consent form (ICF) for each potential subject.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Foothills Medical Centre
    • Edmonton, Alberta, Canada, T5H 3V9
      • Royal Alexandria Hospital
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Montreal Children's Hospital
• Chile
  • Santiago, Chile, 8207257
    • Hospital Dr Sotero del Rio
  • Santiago, Chile, 8350488
    • Hospital San Juan de Dios
• Poland
  • 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
  • Mazowieckie
    • Warsaw, Mazowieckie, Poland, 00-315
      • Szpital Kliniczny im. Ks, Anny Mazowieckiej Klinika Neonatologii
  • Wielkopolskie
    • Poznan, Wielkopolskie, Poland, 60-535
      • Ginekologiczno-Polozniczy Szpital Klinicznym UM im. Karola Marcinkowskiego w Poznan i u Katedra Neonatologii
• United States
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University Medical Center
    • 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
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University Of Louisville
  • Nebraska
    • Omaha, Nebraska, United States, 68105
      • University of Nebraska Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University College of Physicians and Surgeons, New York Presbyterian Hospital - Morgan Stanley Children's Hospital
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
      • New Hanover Regional Medical Center
  • Oregon
    • Portland, Oregon, United States, 97225
      • Providence St. Vincent Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women and Infants Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 6 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Informed consent from a legally authorized representative.
2. Gestational age 26 to 28 completed weeks post menstrual age (PMA).
3. Successful implementation of controlled nCPAP within 90 minutes after birth.
4. Spontaneous breathing.
5. Chest radiograph consistent with RDS.
6. Within the first 20 hours after birth, have an nCPAP of 5 to 6 cm H2O to maintain oxygen saturation measured by pulse oximetry (SpO2) of 88% to 95% with a fraction of inspired oxygen (FiO2) of 0.25 to 0.50 that is clinically indicated for at least 30 minutes. Transient (<10 minutes) FiO2 excursions below 0.25 or above 0.50 did not reset the 30 minute requirement.

Exclusion Criteria:

1. Heart rate that cannot be stabilized above 100 beats/minute within 5 minutes of birth.
2. Recurrent episodes of apnea occurring after the initial newborn resuscitation period (ie, 10 minutes after birth) requiring intermittent positive pressure breaths using inflating pressures above the set CPAP pressure administered manually or mechanically through any patient interface.
3. A 5 minute Apgar score < 5.
4. Major congenital malformation(s) and cranial/facial abnormalities that preclude nCPAP, diagnosed antenatally or immediately after birth.
5. Other diseases or conditions potentially interfering with cardiopulmonary function (eg, hydrops fetalis or congenital infection such as TORCH).
6. Known or suspected chromosomal abnormality or syndrome.
7. Premature rupture of membranes (PROM) > 2 weeks.
8. Evidence of hemodynamic instability requiring vasopressors or steroids for hemodynamic support and/or presumed clinical sepsis.
9. Need for endotracheal intubation and mechanical ventilation.
10. Has been administered: another investigational agent or investigational medical device, any other surfactant agent, steroid treatment after birth.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 50 mg/kg; Lucinactant for inhalation 50 mg total phospholipids (TPL)/kg with nCPAP 1 repeat dose allowed if repeat dosing criteria are met.	Combination product: Lucinactant for inhalation; Lucinactant for inhalation refers to the active investigational agent, lucinactant, in combination with the investigational delivery device (drug-device combination product); Other Names: AEROSURF®
Experimental: 75 mg/kg; Lucinactant for inhalation 75 mg TPL/kg with nCPAP 1 repeat dose allowed if repeat dosing criteria are met.	Combination product: Lucinactant for inhalation; Lucinactant for inhalation refers to the active investigational agent, lucinactant, in combination with the investigational delivery device (drug-device combination product); Other Names: AEROSURF®
Experimental: 100 mg/kg; Lucinactant for inhalation 100 mg TPL/kg with nCPAP 1 repeat dose allowed if repeat dosing criteria are met.	Combination product: Lucinactant for inhalation; Lucinactant for inhalation refers to the active investigational agent, lucinactant, in combination with the investigational delivery device (drug-device combination product); Other Names: AEROSURF®
Experimental: 150 mg/kg; Lucinactant for inhalation 150 mg TPL/kg with nCPAP 1 repeat dose will be allowed if repeat dosing criteria are met.	Combination product: Lucinactant for inhalation; Lucinactant for inhalation refers to the active investigational agent, lucinactant, in combination with the investigational delivery device (drug-device combination product); Other Names: AEROSURF®
Active Comparator: nCPAP alone; nCPAP therapy alone	Device: nCPAP alone; nCPAP therapy; Other Names: nasal continuous positive airway pressure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Peri-Dosing Adverse Events - Initial Dose	Number of Participants with adverse events that were experienced during the initial study treatment	Randomization to 24 Hours Post Randomization
Number of Participants With Air Leak	Number of participants with air leak (includes pneumothorax, pulmonary interstitial emphysema (PIE), pneumomediastinum, pneumopericardium, subcutaneous emphysema)	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Worsening of Respiratory Status Criteria	Number of participants with worsening in one of 12 respiratory status criteria through 72 hours post randomization (need for additional surfactant therapy, desaturation < 80%, heart rate < 100 bpm, sustained fraction of inspired oxygen (FiO2) > 0.50, arterial carbon dioxide (PCO2) > 65 mmHg, sustained apnea, persistent arterial pH < 7.2, intubation for any reason, nCPAP > 7 cmH2O, initiation of intermittent positive pressure ventilation, death, principal investigator determination of worsening status)	Randomization to 72 Hours Post Randomization
Bronchopulmonary Dysplasia	Number of participants with bronchopulmonary dysplasia (BPD) and number of participants alive and without BPD at 36 weeks post-menstrual age (PMA)	Randomization to 36 weeks PMA
Number of Participants With Nasal Continuous Positive Airway Pressure (nCPAP) Failure	Participants who required intubation for mechanical ventilation or surfactant administration were defined as having failed nCPAP	Randomization to 72 Hours Post Randomization
Death	Number of participants who died during the study	Randomization to 36 weeks PMA
FiO2	Observed and change from baseline measurements for fraction of inspired oxygen (FiO2). Values represent the amount (fraction) of oxygen in the air the participant inspires; the values themselves do not have units. The normal amount of oxygen in air ("room air") is 21%, or 0.21.	Randomization to 72 hours post randomization
Number of Participants With Complications of Prematurity	Number of participants with pre-specified common complications of prematurity.	Randomization to 36 weeks PMA

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
nCPAP Failure Without Treatment Interruptions	Number of subjects requiring mechanical ventilation or surfactant administration (nCPAP failure) but did not have a treatment interruption	Randomization to 72 Hours Post Randomization

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2015
• Primary Completion (Actual): May 31, 2017
• Study Completion (Actual): August 11, 2017

Study Registration Dates

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

Study Record Updates

• Last Update Posted (Actual): July 23, 2019
• Last Update Submitted That Met QC Criteria: July 17, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Infant, Premature, Diseases; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn
• Other Study ID Numbers: 03-CL-1401

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO