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-445/tezacaftor (TEZ)/ivacaftor (IVA) in subjects with cystic fibrosis who are heterozygous for the F508del mutation and a gating (F/G) or residual function (F/RF) mutation |
Evaluar la seguridad y tolerabilidad a largo plazo de VX-445/tezacaftor (TEZ)/ivacaftor (IVA) en sujetos con fibrosis quística (FQ) que son heterocigóticos para la mutación F508del y una mutación de activación (F/A) o de función residual (F/FR) |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the long-term efficacy of VX-445/TEZ/IVA - To evaluate the pharmacodynamics (PD) of VX-445/TEZ/IVA |
•Evaluar la eficacia a largo plazo de VX-445/TEZ/IVA •Evaluar la farmacodinámica (FD) de VX-445/TEZ/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 ICF (informed consent form), 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 the parent study. 4. Meets at least 1 of the following criteria: - Completed study drug treatment in the parent study. - Had study drug interruption(s) in the parent study, but without prematurely discontinuing study drug in the parent study and completed study visits up to the last scheduled visit of the Treatment Period of the 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) deberá firmar y fechar un FCI y, si procede, un formulario de asentimiento. 2.Voluntad y capacidad para cumplir con las visitas programadas, el plan de tratamiento, las restricciones del estudio, los análisis de laboratorio, los requisitos anticonceptivos y otros procedimientos del estudio. 3.El paciente no ha retirado su consentimiento del estudio original. 4.Cumplimiento de al menos 1 de los siguientes criterios: •Haber finalizado el tratamiento con el medicamento del estudio en el estudio original. •Pacientes con una o más interrupciones del fármaco del estudio en el estudio original, pero sin una suspensión prematura del fármaco del estudio, y que completaron las visitas del estudio hasta la última visita programada del periodo de tratamiento del estudio orginal. 5.Voluntad de permanecer con una pauta terapéutica estable para la FC (según lo especificado en el apartado 9.5) hasta completar la participación en el estudio. |
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E.4 | Principal exclusion criteria |
1. History of any illness or any clinical condition 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 breast-feeding females. All female subjects, regardless of childbearing potential status, 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 the 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 study (other than the parent study). 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. |
1.Antecedentes de cualquier enfermedad o afección clínica que, según la opinión del investigador, pueda generar confusión en los resultados del estudio o suponer un riesgo adicional respecto a la administración del fármaco del estudio al paciente. 2.Mujeres embarazadas y en período de lactancia. Todas las mujeres deben tener, independientemente de su capacidad de concebir, una prueba de embarazo negativa 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 pueda suponer un riesgo adicional para el paciente según la opinión del investigador (p. ej., pacientes con antecedentes de alergia o hipersensibilidad al fármaco del estudio). 4.Partipación actual en un estudio de un fármaco en investigación (distinto del estudio original). Se permite la participación en estudios sin intervención (incluidos los estudios observacionales, estudios de registro y estudios que requieren extracciones de sangre sin que se administre un fármaco del estudio) y en la selección para otro estudio de 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-445/TEZ/IVA based on adverse events (AEs), clinical laboratory values, ECGs, vital signs, and pulse oximetry. |
La seguridad y la tolerabilidad del tratamiento a largo plazo con VX-445/TEZ/IVA en función de acontecimientos adversos (AA), valores analíticos clínicos, ECG, constantes vitales y oximetría de pulso |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety and tolerability assessments: a. AEs: Continuous (signing of ICF until completion of study participation) b. clinical laboratory values, vital signs, pulse oximetry: day 1; day 15; weeks 4, 8, 16, 24, 36, 48, 60, 72, 84, 96; Early Termination of Treatment (ETT) visit (if applicable); Safety Follow-up (SFU) visit (if applicable) c. ECGs: day 1; day 15; weeks 4, 8, 24, 48, 72, 96; ETT visit (if applicable); SFU visit (if applicable) |
Evaluaciones de seguridad y tolerabilidad: a. AAs: Contínua (firma del ICF hasta la finalización de la participación en el estudio) b. valores clínicos de laboratorio, signos vitales, oximetría de pulso: día 1; día 15; semanas 4, 8, 16, 24, 36, 48, 60, 72, 84, 96; Visita de Terminación Temprana del Tratamiento (ETT) (si aplica); Visita de seguimiento de seguridad (SFU) (si aplica) c. ECGs: día 1; día 15; semanas 4, 8, 24, 48, 72, 96; Visita ETT (si aplica); Visita SFU (si corresponde) |
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E.5.2 | Secondary end point(s) |
- Absolute change in percent predicted forced expiratory volume in 1 second (ppFEV1) - Absolute change in sweat chloride (SwCl) - Absolute change in body mass index (BMI) - Absolute change in BMI z-score - Absolute change in body weight - Absolute change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain (RD) score |
•Cambio absoluto en el porcentaje previsto de volumen espiratorio forzado en 1 segundo (VEFpp1) •Cambio absoluto en la prueba de cloruro en sudor (ClSu) •Cambio absoluto en el índice de masa corporal (IMC) •Cambio absoluto en la puntuación z del IMC •Cambio absoluto en el peso corporal •Cambio absoluto en la puntuación del dominio respiratorio (DR) del Cuestionario sobre la fibrosis quística revisado (CFQ-R) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- ppFEV1: day 1; day 15; weeks 4, 8, 16, 24, 36, 48, 60, 72, 84, 96; ETT visit (if applicable); SFU visit (if applicable) - SwCl: day 1; day 15; weeks 4, 8, 24, 48, 72, 96, ETT visit (if applicable) - BMI: day 1; day 15; weeks 4, 8, 16, 24, 36, 48, 60, 72, 84, 96; ETT visit (if applicable); SFU visit (if applicable) - BMI z-score: day 1; day 15; weeks 4, 8, 16, 24, 36, 48, 60, 72, 84, 96; ETT visit (if applicable); SFU visit (if applicable) - body weight: day 1; day 15; weeks 4, 8, 16, 24, 36, 48, 60, 72, 84, 96; ETT visit (if applicable); SFU visit (if applicable) - CFQ-R RD score: day 1; weeks 4, 8, 24, 48, 72, 96; ETT visit (if applicable); SFU visit (if applicable) |
- ppFEV1: día 1; día 15; semanas 4, 8, 16, 24, 36, 48, 60, 72, 84, 96; Visita ETT (si corresponde); Visita SFU (si corresponde) - SwCl: día 1; día 15; semanas 4, 8, 24, 48, 72, 96, visita ETT (si corresponde) - IMC: día 1; día 15; semanas 4, 8, 16, 24, 36, 48, 60, 72, 84, 96; Visita ETT (si corresponde); Visita SFU (si corresponde) - Puntuación z del IMC: día 1; día 15; semanas 4, 8, 16, 24, 36, 48, 60, 72, 84, 96; Visita ETT (si corresponde); Visita SFU (si corresponde) - peso corporal: día 1; día 15; semanas 4, 8, 16, 24, 36, 48, 60, 72, 84, 96; Visita ETT (si corresponde); Visita SFU (si corresponde) - Puntuación CFQ-R RD: día 1; semanas 4, 8, 24, 48, 72, 96; Visita ETT (si corresponde); Visita SFU (si corresponde) |
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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 | 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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 51 |
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 |
Belgium |
Canada |
Denmark |
France |
Germany |
Ireland |
Italy |
Netherlands |
Spain |
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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LVLS |
Última Visita del Ultimo Paciente |
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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 | 10 |
E.8.9.1 | In the Member State concerned days | 24 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
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 |