E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cystic fibrosis |
Fibrosis quística |
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E.1.1.1 | Medical condition in easily understood language |
Cystic fibrosis |
Fibrosis quística |
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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-659 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are homozygous or heterozygous for the F508del mutation. |
Evaluar la tolerabilidad y la seguridad a largo plazo de VX-659 en combinación triple (CT) con tezacaftor (TEZ) e ivacaftor (IVA) en sujetos con fibrosis quística (FQ) que son homocigotos o heterocigotos para la mutación F508del. |
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E.2.2 | Secondary objectives of the trial |
1) To evaluate the long-term efficacy of VX-659 in TC with TEZ and IVA 2) To evaluate the pharmacodynamics (PD) of VX-659 in TC with TEZ and IVA |
1) Evaluar la eficacia a largo plazo de VX-659 en CT con TEZ e IVA. 2) Evaluar la farmacodinámica (FD) de VX-659 en CT con TEZ e 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 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. Did not withdraw consent from a parent study.
4. Meets at least 1 of the following criteria:
• Completed study drug treatment in a parent study.
• Had study drug interruption(s) in a parent study, but completed study visits up to the last scheduled visit of the Treatment Period of a parent study.
5. Willing to remain on a stable CF treatment regimen through completion of study participation. |
1. El paciente (o su representante legal autorizado) firmará y fechará un formulario de consentimiento informado (FCI) y, cuando proceda, un formulario de asentimiento.
2. El paciente debe estar dispuesto a, y ser capaz de cumplir con, las visitas programadas, el plan de tratamiento, las restricciones del estudio, los análisis clínicos, las directrices sobre anticonceptivos y otros procedimientos del estudio.
3. No retiró el consentimiento de un estudio original.
4. Cumple como mínimo 1 de los 3 siguientes requisitos: • Completó el tratamiento con el fármaco de estudio en el estudio original. • Sufrió una o varias interrupciones en el estudio original, pero completó las visitas del estudio hasta la última visita programada del periodo de tratamiento del estudio original.
5. El paciente debe estar dispuesto a permanecer en un régimen estable de tratamiento de FQ (según se define en la Sección 9.5) hasta la finalización de su participación en el estudio. |
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E.4 | Principal exclusion criteria |
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. Females of childbearing potential 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 a 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 trial (other than a parent study). 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. |
1. Antecedentes de una enfermedad asociada que, en opinión del investigador, podría confundir los resultados del estudio o suponer un riesgo adicional al administrar el fármaco del estudio al paciente.
2. Mujeres embarazadas y en periodo de lactancia. Las mujeres con capacidad de procrear tienen que tener un resultado negativo en la prueba de embarazo en la visita del día 1 antes de recibir la primera dosis del fármaco del estudio.
3. Antecedentes de intolerancia al fármaco en el estudio original que supondrían un riesgo adicional para el paciente en la opinión del investigador (por ej. pacientes con antecedentes de alergia o hipersensibilidad al fármaco del estudio).
4. Participación actual en un estudio de fármaco en investigación (que no sea un estudio original). Se permite la participación en un estudio no intervencionista (incluidos los estudios de observación, estudios de archivos y estudios que requieran extracciones de sangre sin administración de los fármacos del estudio) y participar en procesos de selección para otro estudio Vertex. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety and tolerability of long-term treatment with VX-659 in TC with TEZ and IVA based on adverse events (AEs), clinical laboratory values, ECGs, vital signs, and pulse oximetry. |
Seguridad y tolerabilidad del tratamiento a largo plazo con VX-659 en CT con TEZ e IVA basadas en los acontecimientos adversos (AA), valores de los análisis clínicos, ECG, constantes vitales y pulsioximetría. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Treatment period, ETT visit, Safety Follow-up after last dose. |
Periodo de tratamiento, visita ETT, seguridad de seguimiento después de la última dosis |
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E.5.2 | Secondary end point(s) |
1. Absolute change from baseline in percent predicted forced expiratory volume in 1 second (ppFEV1) 2. Absolute change in sweat chloride (SwCl) 3. Number of pulmonary exacerbations (PEx) 4. Time-to-first PEx 5. Absolute change in body mass index (BMI) 6. Absolute change in BMI z-score 7. Absolute change in body weight 8. Absolute change from baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score |
1. Cambio absoluto en el volumen espiratorio forzado porcentual previsto en 1 segundo (VEFpp1) con respecto al inicio. 2. Cambio absoluto de cloruro en sudor (ClSu). 3. Número de reagudizaciones pulmonares (ReP). 4. Período hasta primera ReP. 5. Variación absoluta en el índice de masa corporal (IMC). 6. Variación absoluta de la puntuación z del IMC. 7. Variación absoluta en el peso corporal. 8. Variación absoluta en el cuestionario sobre la FQ revisado (CFQ-R) respecto al inicio. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Treatment period, ETT Visit, Safety Follow-Up After Last Dose. 2. Day 1,15, Week 4,8,16,24, 96. 3. Treatment period, ETT Visit, Safety Follow-Up After Last Dose. 4. Treatment period, ETT Visit, Safety Follow-Up After Last Dose. 5. Treatment period, ETT Visit, Safety Follow-Up After Last Dose. 6. Treatment period, ETT Visit, Safety Follow-Up After Last Dose. 7. Treatment period, ETT Visit, Safety Follow-Up After Last Dose. 8. Day1, Weeks 4,8,24, 48, 72, 96, ETT Visit, Safety Follow-Up After Last Dose. |
1. Periodo de tratamiento, visita ETT, seguridad de seguimiento después de la última dosis 2. Día 1, 15, Semana 4, 8, 16, 24, 96 3. Periodo de tratamiento, visita ETT, seguridad de seguimiento después de la última dosis 4. Periodo de tratamiento, visita ETT, seguridad de seguimiento después de la última dosis 5. Periodo de tratamiento, visita ETT, seguridad de seguimiento después de la última dosis 6. Periodo de tratamiento, visita ETT, seguridad de seguimiento después de la última dosis 7. Periodo de tratamiento, visita ETT, seguridad de seguimiento después de la última dosis 8. día 1, Semanas 4, 8, 24, 48, 72, 96, Vista ETT,seguridad de seguimiento después de la última dosis |
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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 | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability |
Tolerabilidad |
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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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
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 |
Denmark |
Germany |
Ireland |
Israel |
Norway |
Poland |
Spain |
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
|
The end of study is defined as the last scheduled visit or, for subjects who have been lost to follow-up, the last contact, whichever occurs later, for the latest completing subject in the study. |
El final del estudio se define como la última visita programada o, para los sujetos que se perdieron durante el seguimiento, el último contacto, lo que ocurra más tarde, para el último sujeto que complete el estudio. |
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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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |