E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cystic Fibrosis Homozygous (homozygous for the F508del mutation) |
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E.1.1.1 | Medical condition in easily understood language |
Patients with cystic fibrosis who have two copies of the F508del mutation |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011762 |
E.1.2 | Term | Cystic fibrosis |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic 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 primary objective of this study is to assess the efficacy of ORKAMBI on lung functionality across multiple FRI parameters. |
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E.2.2 | Secondary objectives of the trial |
Secondary outcome variables are Patient Reported Outcome, lung function tests, digital lung auscultation, exercise tolerance and exacerbation frequencies. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Documented diagnosis of CF (homozygous for the F508del mutation must be present, this should be documented in the medical history).
2. Age ≥ 12 years
3. FEV1 ³ 50%
4. Signed informed consent. If patient is a minor, parents/guardians must give written informed consent
5. Patient must be on a stable regimen of CF medication for 4 weeks prior to Visit 1 |
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E.4 | Principal exclusion criteria |
1. FEV1 < 50%
2. Anticipated requirement for hospitalization within the next three weeks
3. History of pneumothorax within the past 6 months prior to Visit 1
4. History of haemoptysis requiring embolization within the past 12 months prior to Visit 1
5. Unable or unwilling to complete study visits or provide follow-up data as required per the study protocol
6. Has taken Intravenous (IV) antibiotics within the past 4 weeks prior to Visit 1
7. Has ongoing exacerbation or Allergic bronchopulmonary aspergillosis (ABPA)
8. Pregnant or lactating female
9. Posttransplant patients
10. Patients with severe hepatic impairment |
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E.5 End points |
E.5.1 | Primary end point(s) |
FRI parameters:
• Specific airway resistance (siRaw)
• Specific Airway volumes (siVaw) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
HRCT scans will be taken at baseline (visit 1) and after 3 months of treatment (Visit 4). |
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E.5.2 | Secondary end point(s) |
FRI parameters:
• Lung and lobe volumes
• Internal airflow distribution
• Airway wall thickness
• Blood vessel volume
• Air trapping
• Deposition of inhaled medications
Spirometry measurements:
• FEV1
• FVC
• FEV1/FVC
Lung Clearance Index (LCI)
Exercise Tolerance:
• 6 Minute Walk Test
Patient Reported Outcome (PRO):
• Borg Category Ratio 10 Scale: measure of the present dyspnea and leg fatigue before and after exercise
• Cystic Fibrosis Questionnaire- Revised (CFQ-R) respiratory domain score: measure Health-Related Quality of Life
Exacerbation frequency:
• Exacerbations requiring oral antibiotics
• Exacerbations requiring intravenous antibiotics |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
HRCT scans will be taken at baseline (visit 1) and after 3 months of treatment (visit 4).
Spirometry will taken at baseline (visit 1), after 1 month of tratement (visit 2), after 2 months of treatment (visit 3) and after 3 months of teratment (visit 4).
LCI will be done at baseline (visit 1) and after 3 months of treatment (visit 4).
6 MWT and PRO will be done at baseline (visit 1) and after 3 months of treatment (visit 4).
Exacerbation frequency will be checked at every visit (1,2,3, and 4). |
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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 | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | 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 | No |
E.8.1.1 | Randomised | No |
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 | No |
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 | No |
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.8.5 | 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 | No |
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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |