E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Nonsense Mutation Cystic Fibrosis |
Fibrosis quística mediada por mutación terminadora |
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E.1.1.1 | Medical condition in easily understood language |
Genetic disease characterized by difficult breathing. Other symptoms include dysfunction of the pancreas, liver, bile duct and intestine, as well as reduced fertility. |
Enfermedad genética caracterizada por dificultad para respirar. Otros síntomas son disfunción del páncreas, hígado, vías biliares e intestino, así como reducción de la fertilidad. |
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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 | 18.0 |
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 of 10-, 10-, 20-mg/kg ataluren in patients with nonsense mutation cystic fibrosis (nmCF), who previously participated in pivotal study PTC124-GD-021-CF, as determined by adverse events and laboratory abnormalities. |
Evaluar la seguridad a largo plazo de 10, 10 y 20 mg/kg de ataluren en pacientes con fibrosis quística mediada por mutación terminadora (FQmt), que participaron previamente en el estudio principal PTC124-GD-021-CF, en función de los acontecimientos adversos y las anomalías analíticas. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the long-term effect of ataluren on pulmonary function - To evaluate the long-term effect of ataluren on pulmonary exacerbation - To determine the long-term effect of ataluren on medical interventions - To evaluate the long-term effect of ataluren on HRQL - To evaluate the long-term effect of ataluren on general well-being - To assess long-term ataluren plasma exposure |
- Evaluar el efecto a largo plazo de ataluren sobre la función respiratoria - Evaluar el efecto a largo plazo de ataluren sobre la exacerbación respiratoria - Determinar el efecto a largo plazo de ataluren sobre intervenciones médicas - Evaluar el efecto a largo plazo de ataluren sobre la CVRS - Evaluar el efecto a largo plazo de ataluren sobre el bienestar general - Evaluar la exposición plasmática a ataluren a largo plazo |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Completion of study treatment (placebo or active) in the previous Phase 3, double-blind study protocol (Protocol PTC124-GD-021-CF). 2. Evidence of signed and dated informed consent/assent document(s) indicating that the patient (and/or his parent/legal guardian) has been informed of all pertinent aspects of the trial. 3. In patients who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during the study drug administration and 4-week follow-up period. 4. Willingness and ability to comply with scheduled visits, ataluren administration plan, study procedures, laboratory tests, and study restrictions |
1. Finalización del tratamiento del estudio (placebo o fármaco activo) del protocolo del estudio anterior de fase 3, doble ciego (PTC124-GD-021-CF). 2. Documento o documentos de consentimiento/asentimiento informado firmados y fechados que indiquen que el paciente (y/o su padre/madre/tutor) ha sido informado de todos los aspectos relativos al ensayo. 3. En pacientes que sean sexualmente activos, disposición a abstenerse de mantener relaciones sexuales o a utilizar un método anticonceptivo de barrera o médico durante la administración del fármaco del estudio y el período de seguimiento de 4 semanas. 4. Disposición y capacidad de cumplir todas las visitas programadas, el plan de administración de ataluren, los procedimientos del estudio, las pruebas analíticas y las restricciones del studio. |
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E.4 | Principal exclusion criteria |
1. Known hypersensitivity to any of the ingredients or excipients of the study drug. 2. Ongoing participation in any other therapeutic clinical trial. 3. Prior or ongoing medical condition (eg, concomitant illness, psychiatric condition, behavioral disorder, alcoholism, drug abuse), medical history, physical findings, ECG findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the patient, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results. |
1. Hipersensibilidad conocida a cualquiera de los componentes o excipientes del fármaco del estudio. 2. Participación actual en otro ensayo clínico terapéutico. 3. Trastornos (por ejemplo, enfermedades concomitantes, trastorno psiquiátrico, trastornos de la conducta, alcoholismo, abuso de sustancias), antecedentes médicos, hallazgos físicos, hallazgos de ECG o anomalías analíticas previos o presentes que, en opinión del investigador, podrían afectar negativamente a la seguridad del paciente, hacer improbable la finalización del tratamiento o seguimiento o confundir la evaluación de los resultados del estudio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety profile characterized by type, frequency, severity, timing, and relationship to ataluren of any adverse events (AEs) or laboratory abnormalities. |
Perfil de seguridad definido por el tipo, la frecuencia, intensidad, cronología y relación con ataluren de todos los acontecimientos adversos (AAs) o anomalías analíticas. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
AEs assessment and documention at : Screening, Week 12, 24, 36, 48, 60, 72, 84, 96, 4-Week Post-Treatment. Reporting of AEs of concern at any time between visits. |
Evaluación de los AAs y documentación: Selección, Semana 12, 24, 36, 48, 60, 72, 84, 96, seguimiento de 4 semanas post-tratamiento.
Información de los AAs de interés en todo momento entre las visitas. |
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E.5.2 | Secondary end point(s) |
1- Changes in FEV1, FVC, and FEF25-75 as assessed by spirometry 2- Rate, incidence, and duration of pulmonary exacerbations (modified Fuchs criteria) 3- Incidences, rates, and durations of interventions (eg, antibiotic use and hospitalization) and disruptions to daily living (eg, missed school or work) resulting from pulmonary symptoms 4- Changes in CFQ-R domains 5- Changes in body weight and BMI 6- New Pseudomonas aeruginosa lung infection 7- Pre-dose ataluren plasma concentrations prior to morning ataluren administration at each clinic visit as assessed by a validated bioanalytical method 8- Change from baseline in other safety parameters (eg, vital signs) |
- Variación del FEV1, la FVC y el FEF25-75 evaluada mediante espirometría - Tasa, incidencia y duración de exacerbaciones respiratorias (criterios de Fuchs modificados) - Incidencias, tasas y duraciones de intervenciones (por ejemplo, uso de antibióticos y hospitalización) e interrupción de las actividades cotidianas (por ejemplo, absentismo escolar o laboral) debido a síntomas respiratorios - Variaciones de los dominios del cuestionario CFQ-R - Variaciones en el peso corporal e IMC - Nueva infección respiratoria por Pseudomonas aeruginosa - Concentración plasmática de ataluren antes de la administración previa a la administración matutina de ataluren en cada visita al centro evaluada mediante un método bioanalítico validado - Variación con respecto al momento basal de otros parámetros de seguridad (por ejemplo, constantes vitals) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endpoints #1, 5 and 8 : Screening, Week 12, 24, 36, 48, 60, 72, 84, 96, 4-Week Post-Treatment.
Secondary endpoints #2, 3, 4, 6 and 7 : Screening, Week 12, 24, 36, 48, 60, 72, 84, 96 |
Criterios de valoración secundarios 1, 5, 8 : Selección, semana 12, 24, 36, 48, 60, 72, 84, 96, seguimiento de 4 semanas post-tratamiento
Criterios de valoración secundarios 2, 3, 4, 6, 7: Selección, semana 12, 24, 36, 48, 60, 72, 84, 96 |
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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 | No |
E.6.7 | Pharmacodynamic | No |
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 46 |
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 |
Argentina |
Australia |
Belgium |
Brazil |
Bulgaria |
Canada |
France |
Germany |
Greece |
Israel |
Italy |
Netherlands |
Poland |
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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Last visit of the last patient |
Última visita del último 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 | |
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 | 7 |