E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
symptomatic emphysema secondary to alpha-1-antitrypsin deficiency |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
This is a phase II proof of concept study to investigate efficacy, safety and tolerability of 1.0 mg of RO3300074 when administered once daily for 12 months (52 weeks) compared with placebo. The primary efficacy measure is the change from baseline in 12 months of the 15th percentile of the lung density adjusted for the lung volume as obtained by computer tomography (spiral CT scanner) using lung density histograms |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives include assessment of lung function including spirometry, TLco, lung volumes, arterial blood gases, exercise, quality of life, assessments of dyspnea, and plasma biomarkers. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Men >= 30 years of age with AATD of the Pi Z or Pi Null phenotype. 2. Women >= 30 years of age with AATD of the Pi Z or Pi Null phenotype beyond child-bearing potential defined as women who are more than 5 years post menopausal unless they have had a hysterectomy or bilateral oophorectomy. 3. Non-smokers with clinical diagnosis of emphysema with confirmation by radiographic imaging (ex-smokers must have stopped smoking for 6 months prior to enrollment). 4. TLco (KCO ) < 60% of the predicted normal value. 5. Base-line FEV1 <= 70 % of the predicted normal value for gender, age, and height and measured before administration of a bronchodilator.
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E.4 | Principal exclusion criteria |
1. AATD patients on concomitant Prolastin replacement therapy. 2. Psychiatric disorders requiring medication or hospitalization, or with suicide attempt within the last 7 years. 3. More than 3 exacerbations of pulmonary symptoms, requiring treatment with oral steroids, or antibiotics, within 12 months prior to this study. 4. Patients with giant bullous disease. 5. Significant other medical conditions, which in the opinion of the investigator, will interfere with the patient’s ability to perform the study tests. 6. Hypertriglyceridemia 300mg/dl with therapy 7. Concomitant medications which are inhibitors or inducers of CYP 450 3A4 activity |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy measure is the change from baseline in 12 months of the 15th percentile of the lung density adjusted for the lung volume as obtained by computer tomography (spiral CT scanner) using lung density histograms. The CT densitometry measurements will be performed at baseline, after 28 and after 52 weeks of treatment. |
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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 | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
E.8.1.5 | Parallel group | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |