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-445/tezacaftor (TEZ)/ivacaftor (IVA) in subjects with cystic fibrosis who are heterozygous for the F508del mutation and a gating (F/G) or residual function (F/RF) mutation |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the long-term efficacy of VX-445/TEZ/IVA - To evaluate the pharmacodynamics (PD) of VX-445/TEZ/IVA |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject (or his or her legally appointed and authorized representative) will sign and date an ICF (informed consent form), and, when appropriate, an assent form. 2. Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures. 3. Did not withdraw consent from the parent study. 4. Meets at least 1 of the following criteria: - Completed study drug treatment in the parent study. - Had study drug interruption(s) in the parent study, but without prematurely discontinuing study drug in the parent study and completed study visits up to the last scheduled visit of the Treatment Period of the parent study. 5. Willing to remain on a stable CF treatment regimen through completion of study participation. |
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E.4 | Principal exclusion criteria |
1. History of any illness or any clinical condition 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. 2. Pregnant and breast-feeding females. All female subjects, regardless of childbearing potential status, must have a negative pregnancy test at the Day 1 Visit before receiving the first dose of study drug. 3. History of drug intolerance in the parent study that would pose an additional risk to the subject in the opinion of the investigator. (e.g., subjects with a history of allergy or hypersensitivity to the study drug). 4. Current participation in an investigational drug study (other than the parent study). Participation in a non-interventional study (including observational studies, registry studies, and studies requiring blood collections without administration of study drug) and screening for another Vertex study is permitted. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety and tolerability of long-term treatment with VX-445/TEZ/IVA based on adverse events (AEs), clinical laboratory values, ECGs, vital signs, and pulse oximetry. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety and tolerability assessments: a. AEs: Continuous (signing of ICF until completion of study participation) b. clinical laboratory values, vital signs, pulse oximetry: day 1; day 15; weeks 4, 8, 16, 24, 36, 48, 60, 72, 84, 96; Early Termination of Treatment (ETT) visit (if applicable); Safety Follow-up (SFU) visit (if applicable) c. ECGs: day 1; day 15; weeks 4, 8, 24, 48, 72, 96; ETT visit (if applicable); SFU visit (if applicable) |
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E.5.2 | Secondary end point(s) |
- Absolute change in percent predicted forced expiratory volume in 1 second (ppFEV1) - Absolute change in sweat chloride (SwCl) - Absolute change in body mass index (BMI) - Absolute change in BMI z-score - Absolute change in body weight - Absolute change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain (RD) score |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- ppFEV1: day 1; day 15; weeks 4, 8, 16, 24, 36, 48, 60, 72, 84, 96; ETT visit (if applicable); SFU visit (if applicable) - SwCl: day 1; day 15; weeks 4, 8, 24, 48, 72, 96, ETT visit (if applicable) - BMI: day 1; day 15; weeks 4, 8, 16, 24, 36, 48, 60, 72, 84, 96; ETT visit (if applicable); SFU visit (if applicable) - BMI z-score: day 1; day 15; weeks 4, 8, 16, 24, 36, 48, 60, 72, 84, 96; ETT visit (if applicable); SFU visit (if applicable) - body weight: day 1; day 15; weeks 4, 8, 16, 24, 36, 48, 60, 72, 84, 96; ETT visit (if applicable); SFU visit (if applicable) - CFQ-R RD score: day 1; weeks 4, 8, 24, 48, 72, 96; ETT visit (if applicable); SFU visit (if applicable) |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
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) | 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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 51 |
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 |
Canada |
United States |
France |
Netherlands |
Spain |
Germany |
Italy |
Belgium |
Denmark |
Ireland |
United Kingdom |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 24 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |