E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Nonsense Mutation 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 | 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 determine the long-term safety and tolerability of 10-, 10-, 20- mg/kg ataluren in patients with nmCF who completed participation in the double-blind study (Study 009) as assessed by adverse events and laboratory abnormalities. |
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E.2.2 | Secondary objectives of the trial |
To determine the efficacy and safety of ataluren as assessed by spirometry (FEV1), pulmonary exacerbation rate, and other safety parameters (eg, 12-lead ECG measurements, vital signs).
To determine the efficacy of ataluren as assessed by other parameters of pulmonary function (FVC and FEF25-75), and changes in body weight BMI. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Evidence of signed and dated informed consent/assent document(s) indicating that the subject (and/or parent/legal guardian) has been informed of all pertinent aspects of the trial.
2. Evidence of completed participation in the double-blind study, PTC124-GD-009-CF (Study 009).
3. Body weight ≥16 kg.
4. Performance of a valid, reproducible spirometry test using the study-specific spirometer during the screening period.
5. Confirmed screening laboratory values within the central laboratory ranges noted in Table 1 of the protocol.
6. In male and female subjects 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 60-day follow-up period.
7. Willingness and ability to comply with all study procedures and assessments, including scheduled visits, drug administration plan, 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 ataluren (polydextrose, polyethylene glycol 3350, poloxamer 407, mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, vanilla, colloidal silica, or magnesium stearate).
2. Any change (initiation, change in type of drug, dose modification, schedule modification, interruption, discontinuation, or re-initiation) in a chronic treatment/prophylaxis regimen for CF or for CF-related conditions within 4 weeks prior to screening or between screening and randomization.
3. Chronic use of systemic tobramycin within 4 weeks prior to screening.
4. Exposure to another investigational drug within 4 weeks prior to screening.
5. Ongoing participation in any other therapeutic clinical trial.
6. Evidence of pulmonary exacerbation or acute upper or lower respiratory tract infection (including viral illnesses) within 3 weeks prior to screening or between screening and randomization.
7. Treatment with intravenous antibiotics within 3 weeks prior to screening.
8. Ongoing immunosuppressive therapy (other than corticosteroids).
9. Ongoing warfarin, phenytoin, or tolbutamide therapy.
10. History of solid organ or hematological transplantation.
11. Major complications of lung disease (including massive hemoptysis, pneumothorax, or pleural effusion) within 8 weeks prior to screening.
12. Known portal hypertension.
13. Positive hepatitis B surface antigen, hepatitis C antibody test, or human immunodeficiency virus (HIV) test.
14. Pregnancy or breast-feeding.
15. Current smoker or a smoking history of ≥10 pack-years (number of cigarette packs/day × number of years smoked).
16. Prior or ongoing medical condition (eg, concomitant illness, alcoholism, drug abuse, psychiatric condition), 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, and laboratory abnormalities |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Screening visit, weeks 1, 16, 32, 48, 64, 80, 96 (end of treatment) and
100 (4-week post-treatment follow-up) |
|
E.5.2 | Secondary end point(s) |
1. Change from baseline to end of treatment in spirometric performance as measured by FEV1
2. Rate of pulmonary exacerbations, as assessed by modified Fuchs (primary definition), and Fuchs and expanded Fuchs criteria
3. Change from baseline in other safety parameters (eg, 12-lead ECG measurements, vital signs)
4. Change from baseline to end of treatment in spirometric performance as measured by FVC and FEF25-75
5. Change from baseline to end of treatment in body weight and BMI |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1, 4, 5: Screening visit, weeks 1, 16, 32, 48, 64, 80, 96 and 100 (4-week post-treatment follow-up)
2: Screening visit, weeks 1 to 96
3: Screening visit, weeks 1 (vital signs only), 16, 32, 48, 64, 80, 96 and 100 (4-week post-treatment follow-up) |
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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.8.3 |
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 | 11 |
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 |
Belgium |
France |
Germany |
Israel |
Italy |
Spain |
Sweden |
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
|
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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |