E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Respiratory Distress Syndrome (RDS) |
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E.1.1.1 | Medical condition in easily understood language |
Breathing difficulty in babies born prematurely |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10021735 |
E.1.2 | Term | Infant respiratory distress syndrome |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038690 |
E.1.2 | Term | Respiratory distress syndrome (neonatal) |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028974 |
E.1.2 | Term | Neonatal respiratory distress syndrome |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 incidence of and time to respiratory failure and/or death due to RDS over the first 72 hours of life, the incidence of BPD at 36 weeks PMA, and change in physiologic parameters (FiO2 and PCO2) over the first 72 hours of life. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed ICF from legally authorized representative (consent may be obtained prenatally, where allowed) 2. Gestational age: a. Part A: 28 0/7 to 32 6/7 completed weeks' gestation PMA b. Part B: 26 0/7 to 28 6/7 completed week´s gestation PMA 3. Successful implementation of non-invasive support or ventilation (preferably bubble CPAP) within a. Part A: 90 minutes after birth b. Part B: 60 minutes after birth 4. Spontaneous breathing 5. Chest radiograph consistent with RDS (may be deferred if in the best medical interest of the subject) 6. Respiratory support: a. Part A: Within the first 20 hours after birth, requires an nCPAP of 5 to 7 cm H2O with an FiO2 of ≥0.25 (>0.21 for neonates 28 weeks PMA) to 0.4 that is clinically indicated for at least 30 minutes to maintain SpO2 of 90% to 95%. b. Part B: Within the first 12 hours after birth, requires an nCPAP of 5 to 7 cm H2O with an FiO2 of >0.21 to 0.4 that is clinically indicated for at least 20 minutes to maintain SpO2 of 90% to 95%. Transient (<10 minutes) FiO2 excursions outside this range do not reset the time requirement. |
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E.4 | Principal 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 (eg, 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 invasive MV at any time before enrollment into the study 10. The administration (or plan for administration) of any the following: a) Another investigational agent or investigational medical device b) Any other surfactant agent c) 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for this study is the incident of respiratory failure or death due to RDS within the first 72 hours of life. A subject will be categorized as having respiratory failure due to RDS if either of the following occur: 1. Intubation for MV and/or surfactant administration (with or without MV) within 72 hours of life 2. The subject meets at least 1 of the following criteria, regardless of whether endotracheal intubation is performed: a. A sustained (≥ 60 minutes) need for FiO2 > 0.45 to maintain an SpO2 > 90% to 95% b. A sustained (on ≥ 2 consecutive observations > 60 minutes apart) transcutaneous PCO2 > 65 mm Hg c. nCPAP > 8 cm H2O Death due to RDS is any death whose primary cause is respiratory failure due to RDS. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
the first 72 hours of life |
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E.5.2 | Secondary end point(s) |
Secondary Endpoints: The secondary endpoints of this study include the evaluation of the following from the time of initiation of study treatment until study completion: 1. Time to respiratory failure or death due to RDS 2. Incidence rate of BPD at 36 weeks PMA 3. All-cause mortality 4. Incidence rate of survival without BPD at 36 weeks PMA 5. Incidence rate of air leak
Tertiary Endpoints: The tertiary endpoints of this study include the evaluation of the following from the time of initiation of study treatment until study completion: 1. Incidence rates of common complications of prematurity other than air leak 2. Change from baseline in FiO2 and/or transcutaneous PCO2 over the first 72 hours of life
Safety Endpoints: The following safety measures are to be documented in the electronic case report form (eCRF): 1. Survival (date and time of death, if applicable) 2. AEs, including adverse device effects (ADEs) and AEs of special interest including peridosing events, complications related to placement of bi-nasal prongs, and air leak 3. Concomitant medications 4. Use of respiratory support and supplemental O2, including the following: a) Need for endotracheal intubation and MV b) Mode of respiratory support (including supplemental oxygen) and important parameters for that mode 5. Complications of prematurity 6. Physical examinations 7. Tolerability of lucinactant for inhalation 8. Incidence of air leak 9. Assessments of the following: a) Vital signs b) O2 saturation, as determined by pulse oximetry (SpO2) c) Serum electrolyte measurements d) Defecation e) Chest radiography prior to intubation |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
New treatment Part B will be open label |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
nCPAP - Continuous positive airway pressure/nasal |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Chile |
Colombia |
Hungary |
Ireland |
Netherlands |
Poland |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Longer-Term Follow-Up - visit at 1-Year Corrected Age |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |