E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Nonsense-Mutation-Mediated Cystic Fibrosis |
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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 |
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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 | 14.0 |
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 |
The primary objective of this study is to evaluate the long-term safety of ataluren in patients with nmCF, as determined by adverse events and laboratory abnormalities. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives provide a comprehensive evaluation of the effects of ataluren on major clinical manifestations of CF and on the pathophysiology of the disease, and include the following: • To determine the long-term effect of ataluren on pulmonary function • To determine the long-term effect of ataluren on pulmonary exacerbation • To determine the long-term effect of ataluren on medical interventions • To determine the long-term effect of ataluren on health-related quality of life (HRQL) • To determine the long-term effect of ataluren on general well-being • To determine the long-term effect of ataluren on CF pulmonary pathology • To evaluate the long-term pharmacologic activity of ataluren in CF • To determine long-term compliance with ataluren therapy • To assess long-term ataluren plasma exposure |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Completion of ~48 weeks of blinded study drug treatment in the previous Phase 3 study (Study PTC124-GD-009-CF). 2. Evidence of signed and dated informed consent/assent document(s) indicating that the subject (and/or his/her parent/legal guardian) has been informed of all pertinent aspects of the study. Note: If the study candidate is considered a child under local regulation, a parent or legal guardian must provide written consent prior to initiation of study screening procedures and the study candidate may be required to provide written assent. The rules of the responsible Institutional Review Board/Institutional Ethics Committee (IRB/IEC) regarding whether one or both parents must provide consent and the appropriate ages for obtaining consent and assent from the subject should be followed. 3. In subjects who are sexually active, willingness to abstain from sexual intercourse or employ a highly effective barrier or medical method of contraception during ataluren administration and within 60 days of the last administration of the study drug. 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 (polydextrose, polyethylene glycol 3350, poloxamer 407, mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, vanilla, colloidal silica, magnesium stearate). 2. Current pregnancy or lactating, or pregnancy or lactating during the preceding Phase 3 study (Study PTC124-GD-009-CF). 3. Ongoing participation in any other therapeutic clinical trial. 4. 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 subject, 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 or laboratory abnormalities. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Long-term safety of ataluren in patients with nonsense mutation CF, as determined by adverse events and laboratory abnormalities. |
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E.5.2 | Secondary end point(s) |
• Forced expiratory volume in 1 second (FEV1) • Forced vital capacity (FVC) • Incidence, rate, severity, and duration of pulmonary exacerbations • Respiratory HRQL as assessed by the CFQ-R respiratory domain • Compliance with study drug treatment • Ataluren plasma exposure • Antibiotic use and hospitalization due to CF-related symptoms • Disruptions to school or work due to CF-related symptoms • Body weight • Lung computerized tomography CF score • Nasal transepithelial potential difference (TEPD) • Sweat chloride concentration |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All measures and laboratory values will be collected at the relevant study visits, from visit 1 to the post-treatment follow-up, based on the schedule of assessments. CFQ-R will be administered before treatment to establish a baseline and then every 8 to 16 weeks throughout the study. Ataluren compliance will be assessed at visits 1 through 13. Pre-dose (trough) ataluren plasma concentrations will be assessed prior to morning ataluren administration at each clinic visit. |
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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 | 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 | No |
E.8.1.2 | Open | No |
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.8.3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 |
Israel |
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 subject |
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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 | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |