E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Nonsense Mutation Cystic Fibrosis |
|
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. |
|
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 | 18.1 |
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 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. |
|
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 |
|
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 |
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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. |
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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. |
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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. |
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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) |
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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 |
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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 | Yes |
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 | 9 |
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 |
|
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
|
Last visit of the last patient |
|
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 | 1 |
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 |