E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | |
E.1.1.1 | Medical condition in easily understood language |
Cystic fibrosis in patients homozygous for the F508del-CFTR mutation |
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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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the long-term safety of LUM/IVA combination therapy in subjects aged 2 years and older with CF, homozygous for F508del |
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E.2.2 | Secondary objectives of the trial |
To evaluate the pharmacodynamics (PD) of long-term LUM/IVA combination therapy in subjects aged 2 years and older with CF, homozygous for F508del |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Subjects entering the Treatment Cohort must meet the following criteria: a. Completed 24 weeks of LUM/IVA treatment and the Safety Follow-up Visit in Study VX15-809-115 Part B (Study 115B, NCT02797132) 2. Subjects entering the Observational Cohort must meet 1 of the following criteria: a. Completed 24 weeks of LUM/IVA treatment and the Safety Follow-up Visit in Study 115B, but do not want to enroll in the Treatment Cohort b. Received at least 4 weeks of LUM/IVA treatment and completed visits up to Week 24 and the Safety Follow-up Visit, if required, of Study 115B but are not taking LUM/IVA at the end of the Study 115B Treatment Period (i.e., Week 24) because of a drug interruption and either did not receive Vertex approval to enroll in the Treatment Cohort or do not want to enroll in the Treatment Cohort c. Permanently discontinued LUM/IVA in Study 115B after receiving at least 4 weeks of treatment and remained in the study from the time of treatment discontinuation through the Week 24 Visit and Safety Follow-up Visit, if required 3. Willing to remain on a stable CF medication regimen through the Safety Follow-up Visit |
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E.4 | Principal exclusion criteria |
Treatment Cohort Only: 1. Prematurely discontinued LUM/IVA treatment in Study 115B 2. History of any comorbidity or laboratory abnormality that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering LUM/IVA to the subject 3. History of drug intolerance or other serious reactions to LUM/IVA in Study 115B that would pose an additional risk to the subject in the opinion of investigator, and which should be discussed with the Vertex medical monitor 4. Subjects with a history of allergy or hypersensitivity to LUM/IVA 5. Liver function test (LFT) abnormality meeting criteria for LUM/IVA treatment interruption at the completion of Study 115B, for which no convincing alternative etiology is identified 6. QTc value at the completion of Study 115B that would pose an additional risk to the subject in the opinion of investigator, and which should be discussed with the Vertex medical monitor 7. History of poor compliance with LUM/IVA and/or procedures in Study 115B as deemed by the investigator 8. Participation in an investigational drug trial (including studies investigating LUM and/or IVA) other than Study 115B |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety and tolerability assessments based on the number of subjects with adverse events (AEs) and serious adverse events (SAEs) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline through safety follow-up (up to 98 weeks) |
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E.5.2 | Secondary end point(s) |
1. Absolute change from baseline in sweat chloride 2. Absolute change from baseline in body mass index (BMI) 3. Absolute change from baseline in BMI-for-age Z-score 4. Absolute change from baseline in weight 5. Absolute change from baseline in weight-for-age Z-score 6. Absolute change from baseline in stature 7. Absolute change from baseline in stature-for-age Z-score 8. Time-to-first pulmonary exacerbation 9. Number of pulmonary exacerbations 10. Number of Cystic Fibrosis (CF)-related hospitalizations 11. Absolute change from baseline in fecal elastase-1 (FE-1) levels 12. Absolute change from baseline in serum levels of immunoreactive trypsinogen (IRT) 13. Change from baseline in sputum microbiology cultures 14. Absolute change from baseline in lung clearance index (LCI)2.5 15. Absolute change from baseline in LCI5.0
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. From baseline through 96 weeks 2. From baseline through 96 weeks 3. From baseline through 96 weeks 4. From baseline through 96 weeks 5. From baseline through 96 weeks 6. From baseline through 96 weeks 7. From baseline through 96 weeks 8. From baseline through 96 weeks 9. From baseline through 96 weeks 10. From baseline through 96 weeks 11. From baseline through 96 weeks 12. From baseline through 96 weeks 13. From baseline through 96 weeks 14. From baseline through 96 weeks 15. From baseline through 96 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 | No |
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) | 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 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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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.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 15 |