E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cystic Fibrosis |
Fibrosi cistica |
|
E.1.1.1 | Medical condition in easily understood language |
Cystic Fibrosis |
Fibrosi cistica |
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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 | 17.1 |
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 efficacy of VX-661 in combination with ivacaftor in subjects with CF who are heterozygous for the F508del mutation on the CFTR gene and a second CFTR allele with a gating defect that is clinically demonstrated to be ivacaftor responsive |
Valutare l’efficacia di VX-661 in combinazione con ivacaftor in soggetti affetti da FC, eterozigoti per la mutazione F508del del
gene CFTR e portatori di una mutazione CFTR sul secondo allele con un difetto di gating responsivo a ivacaftor sulla base di evidenze cliniche
|
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety of VX-661 in combination with ivacaftor
To investigate the pharmacokinetics (PK) of VX-661 and its metabolites, M1 and M2 (M1-661 and M2-661, respectively) and ivacaftor and its metabolite M1 (M1 ivacaftor)
|
Valutare la sicurezza di VX-661 in combinazione con ivacaftor
Analizzare la farmacocinetica (pharmacokinetics, PK) di VX-661 e dei suoi metaboliti,
M1 ed M2 (M1-661 e M2-661, rispettivamente) e di ivacaftor e del suo
metabolita M1 (M1-ivacaftor)
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Heterozygous for F508del-CFTR mutation and a second CFTR allele with a gating defect that is clinically demonstrated to be ivacaftor responsive
• FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height during screening
• Stable CF disease as judged by the investigator. |
• Eterozigoti per F508del-CFTR e portatori di una mutazione CFTR
sul secondo allele con un difetto di gating responsivo a ivacaftor sulla base di evidenze
cliniche
• Volume espiratorio forzato in 1 secondo (forced expiratory volume in one second, FEV1) ≥ 40% e ≤ 90% del valore normale previsto per età, sesso e altezza durante lo Screening
• Malattia FC stabile in base al giudizio dello sperimentatore.
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E.4 | Principal exclusion criteria |
• 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 pregnancy test at Screening and Week -4 Visits).
• Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements
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• Anamnesi di qualsiasi comorbilità che, in base al giudizio dello sperimentatore,
possa confondere i risultati dello studio o esporre il soggetto a un rischio aggiuntivo durante la
somministrazione del farmaco dello studio.
• Donne in gravidanza e allattamento (le donne fertili devono
risultare negative al test di gravidanza allo Screening e alle Visite della Settimana -4).
• Soggetti fertili sessualmente attivi che non sono disposti ad attenersi ai requisiti contraccettivi
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E.5 End points |
E.5.1 | Primary end point(s) |
Absolute change in percent predicted forced expiratory volume in 1 second (FEV1) from baseline |
Variazione assoluta del volume espiratorio forzato in 1 secondo (FEV1) previsto in percentuale dal basale |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
• Relative change in percent predicted FEV1 from baseline through Week 8
• Absolute change in sweat chloride from baseline through Week 8
• Absolute change in Cystic Fibrosis Questionnaire – Revised (CFQ-R) respiratory domain score from baseline through Week 8
• Safety and tolerability assessments based on adverse events (AEs), clinical laboratory values, standard 12-lead electrocardiograms (ECGs), vital signs, and pulse oximetry; from screening through 4 weeks after receiving last dose
• PK parameters of VX-661, M1-661, M2-661, ivacaftor, and M1 ivacaftor through Week 8 |
Variazione relativa del FEV1 previsto in percentuale dal basale fino alla Settimana
8
• Variazione assoluta del cloruro nel sudore dal basale fino alla Settimana 8
• Variazione assoluta nel punteggio del dominio respiratorio del Questionario sulla fibrosi cistica – rivisto (cystic fibrosis questionnaire-revised, CFQ-R) dal basale fino alla Settimana 8
• Valutazioni della sicurezza e della tollerabilità sulla base di eventi avversi (EA),
valori clinici di laboratorio, elettrocardiogrammi (ECG) standard a 12 derivazioni,
segni vitali e pulsossimetria dallo Screening fino a 4 settimane dopo
la ricezione dell’ultima dose
• Parametri PK
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Weeks 8 and 12 |
Settimane 8 e 12 |
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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 | Yes |
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 | 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 | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 19 |
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 |
Belgium |
Canada |
France |
Ireland |
Italy |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |