E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cystic Fibrosis |
Fibrosi Cistica |
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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 through 24 weeks of treatment in subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation on the CF transmembrane conductance regulator (CFTR) gene |
Valutare l’efficacia di VX-661 in combinazione con ivacaftor fino a 24 settimane di trattamento in soggetti affetti da fibrosi cistica (FC)
omozigoti per la mutazione F508del del gene regolatore della conduttanza transmembrana della fibrosi cistica (cystic fibrosis transmembrane conductance regulator, CFTR)
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety of VX-661 in combination with ivacaftor through Week 24
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)
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Valutare la sicurezza di VX-661 in combinazione con ivacaftor fino alla Settimana 24
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)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Homozygous for the F508del CFTR mutation, genotype to be confirmed at the Screening Visit
• Confirmed diagnosis of CF defined as a sweat chloride value ≥60 mmol/L by quantitative pilocarpine iontophoresis
• FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height during screening
• Stable CF disease as judged by the investigator
• Willing to remain on a stable CF medication regimen through Week 24 or, if applicable, the Safety Follow up Visit
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• Omozigoti per la mutazione F508del-CFTR, genotipo da confermare
alla Visita di screening
• Conferma della diagnosi di FC definita come valore cloruro nel sudore ≥ 60
mmol/l tramite ionoforesi quantitativa con pilocarpina
• 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 a giudizio dello sperimentatore
• Disponibilità a rimanere in un regime farmacologico stabile per la FC fino alla Settimana 24 o, se pertinente, alla Visita di follow-up di sicurezza
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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.
• An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1 (first dose of study drug)
• Pregnant or nursing females (females of childbearing potential must have a negative pregnancy test at Screening and Day 1)
• Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements
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• Anamnesi di qualsiasi comorbidità che, a giudizio dello sperimentatore, possa confondere i risultati dello studio o esporre il soggetto a un rischio aggiuntivo durante la somministrazione del farmaco dello studio.
• Un’infezione acuta delle vie respiratorie superiori o inferiori, esacerbazione polmonare
o variazioni della terapia (compresi gli antibiotici) per la malattia polmonare
nei 28 giorni precedenti il Giorno 1 (prima dose di farmaco dello studio)
• Donne in gravidanza o allattamento (le donne fertili devono risultare negative al test di gravidanza allo Screening e al Giorno 1)
• 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 through Week 24 |
Variazione assoluta del volume espiratorio forzato in 1 secondo (FEV1) previsto in percentuale dal basale fino alla Settimana 24 |
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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) |
• Relative change in percent predicted FEV1 from baseline through Week 24
• Number of pulmonary exacerbations through Week 24
• Absolute change in body mass index (BMI) from baseline at Week 24
• Absolute change in Cystic Fibrosis Questionnaire – Revised (CFQ-R) respiratory domain score from baseline through Week 24
• 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
• Time to first pulmonary exacerbation through Week 24
• Absolute change in sweat chloride from baseline through Week 24
• Absolute change in BMI z-score from baseline at Week 24 (in subjects <20 years of age at time of screening)
• Absolute change in body weight from baseline at Week 24
• PK parameters of VX-661, M1-661, M2-661, ivacaftor, and M1 ivacaftor through week 24
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• Variazione relativa del FEV1 previsto in percentuale dal basale fino alla Settimana
24
• Numero di esacerbazioni polmonari fino alla Settimana 24
• Variazione assoluta nell’indice di massa corporea (IMC) dal basale alla Settimana 24
• Variazione assoluta nel punteggio del dominio respiratorio del Questionario sulla fibrosi cistica – rivisto (cystic fibrosis questionnaire-revised, CFQ-R) dal basale fino alla Settimana 24
• Valutazioni della sicurezza e della tollerabilità sulla base di eventi avversi (EA), valori clinici di laboratorio, elettrocardiogrammi (ECG) a 12 derivazioni, segni vitali e pulsossimetria dallo screening fino a 4 visite dopo la ricezione dell’ultima dose
• Tempo alla prima esacerbazione polmonare fino alla Settimana 24
• Variazione assoluta del cloruro nel sudore dal basale fino alla Settimana 24
• Variazione assoluta nel punteggio Z dell’IMC dal basale fino alla Settimana 24 (nei soggetti di età < 20 anni al momento dello screening)
• Variazione assoluta nel peso corporeo dal basale alla Settimana 24
• Parametri PK di VX-661, M1-661, M2-661, ivacaftor e M1-ivacaftor fino alla Settimana 24
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Weeks 24 and 28 |
Settimane 24 e 28 |
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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) | No |
E.8.2.2 | Placebo | Yes |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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 |
Canada |
Denmark |
France |
Germany |
Ireland |
Italy |
Netherlands |
Spain |
Sweden |
Switzerland |
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 | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |