E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 14.0 |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the effect of VX-770 on lung clearance index (LCI) in subjects aged 6 years and older with cystic fibrosis (CF) who have the G551D CFTR mutation on at least 1 allele |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the safety of VX-770 in subjects aged 6 years and older with CF who have the G551D CFTR mutation on at least 1 allele
- To evaluate the efficacy of VX-770 in subjects aged 6 years and older with CF who have the G551D CFTR mutation on at least 1 allele
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female subjects with confirmed diagnosis of CF
- Must have the G551D CFTR mutation in at least 1 allele (any known or unknown mutations allowed in second allele)
- FEV1 >90% of predicted normal for age, gender, and height at screening
- LCI threshold at screening greater than the established ULN of 7.4
- 6 years of age or older on the date of signed informed consent form (ICF), and where appropriate, date of assent
- Weight greater than or equal to 15 kg without shoes at screening
- Able to swallow tablets |
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E.4 | Principal exclusion criteria |
- Abnormal renal function at screening, defined as creatinine clearance <75 mL/min/1.73 m2 using the Counahan-Barratt equation (for subjects 6 to 17 years of age) or <50 mL/min using the Cockcroft-Gault equation (for subjects 18 years of age or older)
- History of solid organ or hematological transplantation
- Colonization with organisms associated with a more rapid decline in pulmonary status (e.g., B cenocepacia, B dolosa, and M abcessus) at screening
- Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within the 30 days prior to screening.
- Use of inhaled hypertonic saline treatment. (Subjects who have stopped inhaled hypertonic saline treatment will be eligible to participate, but they must have withheld treatment for 48 hours prior to the screening visit and have undergone a washout period of at least 2 weeks prior to the Period 1 Day 1 visit)
- Concomitant use of any inhibitors or inducers of cytochrome P450 (CYP) 3A, including consumption of certain herbal medications (e.g., St. John’s Wort), and grapefruit/grapefruit juice. Subjects must stop consuming these items 14 days prior to Period 1 Day 1.
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E.5 End points |
E.5.1 | Primary end point(s) |
Absolute change from baseline in Lung Clearance Index (LCI) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Safety as determined by adverse events, clinical laboratory values (chemistry, hematology, coagulation studies, and urinalysis), standard digital electrocardiograms (ECGs), and vital signs
Efficacy as determined by:
• Absolute change from baseline in percent predicted forced expiratory volume in 1 second (FEV1)
• Change from baseline in sweat chloride
• Change from baseline in CF Questionnaire-Revised (CFQ-R)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Safety: 16 weeks; Efficacy: 4 Weeks
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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 | 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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Yes |
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 | Yes |
E.8.2.3 | Other | No |
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 | 3 |
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 |
United Kingdom |
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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The end of the study is the last visit of the last subject undergoing the study. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |