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] - Respiratory Tract Diseases [C08] |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the long-term safety and tolerability of VX-661 in combination with ivacaftor in subjects with CF, homozygous or heterozygous for the F508del-CFTR mutation who are in the Treatment Cohort. |
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E.2.2 | Secondary objectives of the trial |
Treatment Cohort To evaluate the long -term efficacy of VX 661 in combination with ivacaftor for subjects in the Treatment Cohort
Observational Cohort To evaluate the post treatment safety of VX 661 in combination with ivacaftor for subjects in the Observational Cohort
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects entering the Treatment Cohort must meet all of the following criteria: •Elect to enroll in the Treatment Cohort. •Completed study drug treatment during the Treatment Period in a parent study (Studies 103, 106, 107, 108, or 109) or study drug treatment and the Safety Follow up Visit for subjects from Study 111. • Willing to remain on a stable CF medication (and supplement) regimen through the Safety Follow-up Visit.
Subjects entering the Observational Cohort must meet the following criteria: • <18 years of age (age on the date of informed consent/assent in the parent study) • Completed study drug treatment during the Treatment Period in a parent study (Studies 103, 106, 107, 108, or 109) or study drug treatment and the Safety Follow up Visit for subjects from Study 111, but do not elect to enroll in the Study 110 Treatment Cohort; or • Received at least 4 weeks of study drug treatment in a parent study, but do not meet eligibility criteria for enrollment into the Treatment Cohort.
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E.4 | Principal exclusion criteria |
Treatment Cohort: • History of any comorbidity that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject. • Pregnant and nursing females. Females of childbearing potential must have a negative urine pregnancy test at the Day 1 Visit and before receiving the first dose of study drug. • Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements. • History of drug intolerance in the parent study that would pose an additional risk to the subject. • History of poor compliance with study drug and/or procedures in the parent study as deemed by the investigator. • Participation in an investigational drug trial other than Studies 103, 106, 107, 108, 109, and 111 or use of a commercially available CFTR modulator (e.g., Kalydeco). |
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E.5 End points |
E.5.1 | Primary end point(s) |
For the Treatment Cohort: Safety and tolerability of long-term treatment of VX-661 in combination with ivacaftor based on adverse events (AEs), ophthalmologic examinations (subjects <18 years of age, clinical laboratory values (serum chemistry, hematology, coagulation, lipids, vitamins, and urinalysis), standard digital electrocardiograms (ECGs), vital signs, and pulse oximetry
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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) |
For the Treatment Cohort: • Absolute change from baseline in percent predicted forced expiratory volume in 1 second (ppFEV1) • Relative change from baseline in ppFEV1 • Number of pulmonary exacerbations • Absolute change from baseline in body mass index (BMI) • Absolute change from baseline in BMI z score for subjects aged <20 years • Absolute change from baseline in Cystic Fibrosis Questionnaire–Revised (CFQ R) respiratory domain score • Absolute change from baseline in body weight • Absolute change from baseline in body weight z-score for subjects aged <20 years • Absolute change from baseline in height z-score for subjects aged <20 years • Time to first pulmonary exacerbation, • Pharmacokinetic (PK) parameters of VX 661, a VX-661 metabolite (M1 661), ivacaftor, and an ivacaftor metabolite (M1 ivacaftor)
For the Observational Cohort: • Safety, as determined by related serious adverse events (SAEs) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Through 100 weeks (Week 24 for PK endpoint) |
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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 | Yes |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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
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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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 79 |
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 |
Australia |
Austria |
Belgium |
Canada |
Denmark |
France |
Germany |
Ireland |
Israel |
Italy |
Netherlands |
Spain |
Sweden |
Switzerland |
United Kingdom |
United States |
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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 | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial months | 1 |