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 | SOC |
E.1.2 | Classification code | 10010331 |
E.1.2 | Term | Congenital, familial and genetic disorders |
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) |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
PART A Subjects transitioning from Study 659-105 must meet all of the following criteria to be eligible for Part A: 1.Subject (or his or her legally appointed and authorized representative) is willing to sign and date an informed consent form (ICF), 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..Participated in Study 659-105. Current participation is defined as one of the following: •On study drug treatment in Study 659-105 as of the day prior to the Part A Day 1 Visit in this study. •On study drug interruption in Study 659-105 as of the day prior to the Part A Day 1 Visit in this study. Subjects who permanently discontinue VX-659/TEZ/IVA in Study 659-105 for any reason other than enrolling into this study are not eligible. 4.Willing to remain on a stable CF treatment regimen (as defined in Section 9.5) through completion of study participation . Inclusion criteria for subjects resuming participation in Part A of this study after enrolling in another qualifying Vertex study include all of the criteria above AND the following criteria: 5.Completed the ETT visit in another qualified Vertex study before or on same day as the Returning Visit in this study. If more than 30 days have elapsed since the ETT visit in the other qualified Vertex study, approval of the medical monitor is required. 6.Subjects who depart this study more than once to participate in another qualified Vertex study may not return to this study a second time. PART B Subjects who meet all of the following criteria will be eligible for Part B: 1.Subject (or his or her legally appointed and authorized representative) is willing to sign and date a Part B informed consent form (ICF), 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.Completed the Week 96 Visit in Part A. Participation is defined as oneof the following: - On study drug treatment at the end of Part A as of the day prior to the Part B Day 1 Visit in this study. - On study drug interruption at the end of Part A as of the day prior to the Part B Day 1 Visit in this study. 4.Willing to remain on a stable CF treatment regimen (as defined in Section 9.5) through completion of study participation. Inclusion criteria for subjects resuming participation in Part B of this study after enrolling in another qualifying Vertex study include all of the criteria above AND the following criteria: 5.Completed the ETT visit in another qualified Vertex study before or on same day as the Returning Visit in this study. If more than 30 days have elapsed since the ETT visit in the other qualified Vertex study, approval of the medical monitor is required. 6.Subjects who depart this study more than once to participate in another qualified Vertex study may not return to this study a second time. |
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E.4 | Principal exclusion criteria |
PART A Subjects who meet any of the following criteria will NOT be eligible for Part A: 1.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. 2.Pregnant and nursing females. All female subjects must have a negative pregnancy test at the Part A Day 1 Visit before receiving the first dose of study drug. 3.History of drug intolerance in Study 659-105 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 VX-659/TEZ/IVA). 4.Current participation in an investigational drug trial (other than Study 659 105). 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. Subjects resuming participation in Part A of this study after enrolling in another qualifying Vertex study must not meet Part A Exclusion Criteria 1 through 3, and also must not meet any of the following criteria: 5.Pregnant and nursing females. All female subjects must have a negative pregnancy test at the Returning Visit before receiving the first dose of study drug. 6.History of drug intolerance in another qualified Vertex study that would pose an additional risk to the subject in the opinion of the investigator. If protocol-defined interruption criteria is met in another qualified Vertex study, then the subject must remain on study drug interruption until the subject meets criteria in Section 9.8 and receives approval by the medical monitor to resume study drug dosing in this study. 7.Has received the first dose of study drug in the Treatment Period of another qualified Vertex study. 8.Has access to commercially available or managed-access-program supplied VX-445/TEZ/IVA. PART B Subjects who meet any of the following criteria will NOT be eligible for this study: 1.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. 2.Pregnant and nursing females. All female subjects must have a negative pregnancy test at the Part B Day 1 Visit before receiving the first dose of study drug. 3.Current participation in an investigational drug trial. Participation in a noninterventional study (including observational studies, registry studies, and studies requiring blood collections without administration of study drug) and screening for another Vertex study is permitted. Subjects resuming participation in Part B of this study after enrolling in another qualifying Vertex study must not meet Part B Exclusion Criteria 1 through 3, and also must not meet any of the following criteria: 4.Pregnant and nursing females. All female subjects must have a negative pregnancy test at the Returning Visit before receiving the first dose of study drug. 5.History of drug intolerance in another qualified Vertex study that would pose an addition risk to the subject in the opinion of the investigator. If protocol-defined interruption criteria is met in another qualified Vertex study, then the subject must remain on study drug interruption until the subject meets criteria in Section 9.8 and receives approval by the medical monitor to resume study drug dosing in this study. 6.Has received the first dose of study drug in the Treatment Period of another qualified Vertex study. 7.Has access to commercially available or managed-access-program supplied VX-445/TEZ/IVA. |
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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, pulse oximetry, and spirometry. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
assessed throughout the study |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 34 |
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 |
Israel |
United States |
Poland |
Spain |
Switzerland |
Germany |
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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last scheduled visit (or scheduled contact) of the last subject |
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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 | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |