E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cystic fibrosis is the most common fatal inherited disease in the Caucasian population, affecting about 4 in 10.000 children. In cystic fibrosis chloride transport across the respiratory epithelium is deficient, so the mucus contains less water and its viscosity is abnormally increased. Moli1901 corrects the abnormal transport of chloride thereby reducing the formation of mucus plugs and improving clearance. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011763 |
E.1.2 | Term | Cystic fibrosis lung |
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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 |
Study objectives are to establish minimum effective dose (MED), optimal dose, and maximum safe dose (MSD) in this dose-finding study with three different dosage schedules: 1. 2,5 mg/day (0.5 mg/ml; 5 ml) Moli1901, daily 2. 2,5 mg/day (0.5 mg/ml; 5 ml) Moli1901, every other day 3. 2,5 mg/day (0.5 mg/ml; 5 ml) Moli1901, twice a week Additionally, the tolerability of Moli1901 shall be investigated. Primary efficacy criterion (confirmatory evaluation): the change in the percentage of the predicted FEV1 (forced expiratory volume in first second) value
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E.2.2 | Secondary objectives of the trial |
Co-primary criterion (supportive evaluation): the ensemble of two subject reported clinical scores, which are physical dimensions of the self-report, disease-specific quality of life test, the cystic fibrosis questionnaire in the revised version. Secondary efficacy criteria: The change in the percentage of the predicted FVC (forced vital capacity) The change in the percentage of the predicted FEF25-75 (forced expiratory flow 25–75% of FVC) The change in the absolute values of FEV1 (forced expiratory volume in first second) Number of pulmonary exacerbations Number of hospitalization days due to pulmonary exacerbation Dose (cumulative dose) and duration of therapy needed during study participation to treat bronchial obstruction, infection or inflammation (i.e. antibiotics, mucolytics, anti-inflammatory drugs). Time to first pulmonary exacerbation Change in oxygen saturation as measured with pulse oximetry Quality of life questionnaire (cystic fibrosis questionnaire-revised)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Male or female subjects of 12 years of age or older 2.Body mass index equal or above -2 SDS (Standard Deviation Score-According to CDC standards) for 12-19 year old patients and greater/equal 18.5 kg/m2 for adults 20 years old and older 3.Have a confirmed diagnosis of cystic fibrosis: positive sweat chloride value greater/equal 60 mEq/l by quantitative pilocarpine iontophoresis (on at least 2 occasions, if no genotype was determined) and/or genotype with two identifiable mutations consistent with CF, accompanied by one or more clinical features consistent with the CF phenotype Measurement of nasal potential difference could be considered as an additional diagnostic tool, if results of sweat chloride test and genotype test are not unambiguous. Nasal potential difference test can not replace any of the above tests and should not be interpreted in isolation. 4.Have Screening FEV1 between 50% and 85% of predicted. 5.Have oxygen saturation level measured by pulse oximetry (SpO2) greater 90 % on room air
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E.4 | Principal exclusion criteria |
1. Show bronchial hyperresponsiveness as known from previous visits e.g. the subject needs additional puffs of salbutamol (or other beta-2-agonists) more than twice daily. This also applies to subjects who have shown bronchoconstriction to previously administered inhalation therapies or a decrease of FEV1 greater/equal 20% during or after administration of placebo at the screening visit 2.Have shown any evidence for unstable lung function, e.g. have had more than 15% FEV1 variation (difference between highest and lowest measured value in % of highest value measured) in the last 3 months before treatment starts (i.e. visit 2) 3.Have a pulmonary disease such as pneumonia, tuberculosis, or lung cancer 4.Have had an acute upper respiratory tract infection within the last 2 weeks 5.Have had an acute lower respiratory tract infection (requiring antibiotics or hospitalization) within the last 4 weeks 6.Have had an pulmonary exacerbation within the last 4 weeks 7.Have had any changes from routine maintenance therapy within the last 4 weeks 8.Have any scheduled changes to inhaled antibiotics regimen during the course of the study 9.Receive or are planned to receive any treatment via “on-off” regimen (e.g. Tobramycin – TOBI®) 10.Have received the last dose of any “on-off” treatment within the last 6 weeks 11.Have any clinically significant liver, renal, cardiac (as defined by QTc >450 msec (or 0.450 seconds) for males or QTc> 470 msec (or 0.470 seconds) for females), neurological, or hematological disease 12.Have allergic bronchopulmonary aspergillosis or colonization with Burkholderia cepacia 13.Have poorly controlled diabetes mellitus 14.Have smoked more than 3 cigarettes per day within the last 12 months. 15.Have a history of alcohol (> 40g/day) or drug abuse 16.Have participated in an investigational drug study (including Moli1901) within the last 8 weeks 17.Are women of child bearing potential and refuse to use effective contraception or are pregnant or lactating 18.Are unwilling to perform appropriate safe contraception for at least 6 months after investigational product administration
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in the percentage of the predicted FEV1 (forced expiratory volume in first second) value |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 | Information not present in EudraCT |
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 |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 12 |