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 | 19.1 |
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 | 19.1 |
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 | 19.1 |
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 |
The primary objective of this study is to evaluate the safety and tolerability of lucinactant for inhalation, administered as an aerosolized dose in 4 escalating doses to a preterm, neonatal population 26 to 28 completed weeks PMA receiving nCPAP for RDS compared with neonates receiving nCPAP alone. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to determine the maximum tolerated dose of lucinactant as determined by the safety evaluations obtained within each dosing group, and to assess the feasibility of evaluating physiological pulmonary function parameters as a measure of improvement in clinical status in preterm neonates 26 to 28 completed weeks PMA who are receiving nCPAP for RDS, compared with neonates receiving nCPAP alone. |
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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; 2.Gestational age 26 to 28 completed weeks 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, requires an nCPAP of 5 to 6 cm H2O to maintain SpO2 of 88% to 95% with an 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 do not reset the 30 minute requirement.
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E.4 | Principal exclusion criteria |
1.Heart rate that cannot be stabilized above 100 beats per minutes 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/or mechanical ventilation; 10.Has been administered any the following: a)Another investigational agent or investigational medical device, b)Administration of any other surfactant agent, c)Steroid treatment (exposure before birth is acceptable).
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints of this study will be derived from the safety evaluations, including adverse device effects (ADEs) reported from the time of randomization until 36 weeks PMA of upon discharge . |
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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) |
Primary and Secondary Safety and Tolerability Measures: •Primary Observation Period (Day 1 and 2): 1.Survival 2.Use of respiratory support and supplemental oxygen 3.Incidences leading to early discontinuation of aerosolized lucinactant administration 4.Incidence of worsening respiratory status 5.Incidence of air leak 6.AEs, including ADEs (specifically including peri-dosing events and nasal excoriations) 7.Complications of prematurity 8.Concomitant medication 9.Physical exam findings 10.Tolerability of lucinactant for inhalation 11.Assessments of the following: a)Vital signs b)Oxygen saturations (SpO2) c)Partial pressure of carbon dioxide (PCO2) values d)FiO2 values e)Serum electrolyte measurements f)Body weight g)Gastric liquid volume h)Defecation 12.Chest radiography prior to non-emergent intubation, or in cases of worsening respiratory status, if such a procedure does not delay or compromise the emergent care of the subject
•Extended Observation Period (Day 3 until Day 7): 1.Survival 2.Incidences leading to withdrawal from study 3.Incidence of worsening respiratory status 4.AEs, including ADEs 5.Complications of prematurity 6.Concomitant medication 7.Assessment of the following: •Vital signs •O2 saturation values •FiO2 values through 72 hours •PCO2 values through 72 hours 8.Chest radiography prior to non-emergent intubation, or in cases of worsening respiratory status, if such a procedure does not delay or compromise the emergent care of the subject. 9.Use of respiratory support and supplemental oxygen
•Final Observation Period (Day 8 to 36 Weeks PMA or discharge): 1.Survival 2.Incidences leading to withdrawal from study 3.Incidence of worsening respiratory distress 4.AEs, including ADEs 5.Physical exam findings 6.Concomitant medications 7.Use of respiratory support and supplemental oxygen 8.Complications of prematurity |
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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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
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 | 2 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | No |
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 |
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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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 | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |