E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
prematurity-related airway obstruction and inflammation |
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E.1.1.1 | Medical condition in easily understood language |
soreness and narrowing of the airways |
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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 | PT |
E.1.2 | Classification code | 10067775 |
E.1.2 | Term | Upper airway obstruction |
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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006464 |
E.1.2 | Term | Bronchoconstriction |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The overall aim of the research is to establish the reasons why children who were born prematurely have ongoing respiratory symptoms, potentially caused by narrowing of the airways (obstruction), inflammation and structural differences in the lung. The principle objective is to assess if 12 weeks of inhaler treatment can reduce this obstruction and inflammation. |
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E.2.2 | Secondary objectives of the trial |
To obtain updated information on the prevalence of respiratory symptoms (such as wheeze) in children who were born prematurely and investigate how these change over time.
To understand, in detail, the reasons (mechanisms) why inhaler treatment works in some participants, but not in others, by investigating the differences in laboratory markers of disease between responders and non-responders.
To understand more about the structure of the lungs and how this effects their function by comparing results from MRI scans.
To establish a cohort of children born prematurely in Wales for future studies and long-term follow-up |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Part 1: 1) Children aged 7-12 at the time of screening 2) Born at a gestational age ≤34 weeks (NB. sufficient numbers of term-born participants to enroll n=100 controls will also be invited) 3) Resident in the south Wales area whom, in the opinion of the Investigator, are possible to follow up 4) Fully informed proxy consent from parents/guardians and assent from child where possible
Part 2 1) As part 1 plus 2) Preterm-born children found during part 1 to have FEV1 ≤85% predicted NB. Approximately N=100 preterm-born and N=100 term-born controls with %FEV1 >85% predicted will also be invited to Part 2 visit 1
Part 3 1) Preterm-born children found to have FEV1 ≤85% at baseline laboratory visit (part 2, visit 1) who participated in the treatment trial 2) Willing to travel to the University of Sheffield Academic Unit of Radiology, Royal Hallamshire Hospital NB. Approximately n=20 preterm-born and n=20 term-born controls (all with normal lung function) will also be invited to Part 3
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E.4 | Principal exclusion criteria |
Part 1 1) Respiratory tract infection within the last three 3 weeks (will be re-invited at a later date) 2) Congenital abnormalities 3) In the opinion of the Investigator: severe cardiopulmonary defects, or neuromuscular disease, or severe neurodevelopmental impairment Which prohibit the possibility of compliance with the study protocol
Part 2 1) As part 1 plus 2) Known hypersensitivity to salmeterol and/or fluticasone
Part 3 1) Surgery of any type in the previous 2 months 2) Previous brain surgery involving placement of clips or shunts 3) Eye injuries resulting from metal fragments 4) Presence of any metal implants including pacemakers 5) Possibility to be or known to be pregnant
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome will be the difference in pre-and post-treatment percent predicted Forced Expiratory Volume in 1 second (FEV1) after 12 weeks of therapy between the treatment groups |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 12 weeks trial of IMP |
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E.5.2 | Secondary end point(s) |
1) Differences in measures of obstructive airway disease (pulmonary function tests) 2) Differences in response to exercise challenge between treatment groups. 3) Differences in biomarkers of airway inflammation between treatment groups 4) Quality of life, respiratory and neurological symptoms (questionnaire) 5) MRI parameters: apparent diffusion coefficient (ADC) between 3 comparison groups (preterm, FEV1 ≤85% predicted at baseline; preterm control, FEV1 >85% predicted; and term control, FEV1 >90% predicted). 6) Adverse events
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) After 12 weeks trial of IMP 2) After 12 weeks trial of IMP 3) After 12 weeks trial of IMP 4) After 12 weeks trial of IMP 5) Following MRI scan 6) After 12 weeks trial of IMP
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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 | No |
E.6.10 | Pharmacogenetic | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 30 |