| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Moderate persistent asthma | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10003553 | | E.1.2 | Term | Asthma | |
| 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 | • To assess the efficacy as measured by trough FEV1 of a 28 day administration of QAV680 500mg q.i.d compared to placebo in patients with moderate persistent asthma.
• To assess the safety of a 28 day administration of QAV680 500mg q.i.d compared to placebo in patients with moderate persistent asthma. | |
| E.2.2 | Secondary objectives of the trial | • To assess the efficacy as measured by various measures of FEV1 following 28 days of dosing (see protocol for details)
• To assess the pharmacodynamic effect as measured by eNO of a 28 day administration of QAV680 500mg q.i.d compared to placebo
• To assess the pharmacokinetics of multiple doses of QAV680 in patients with moderate asthma.
• To assess the effect of QAV680 on total serum IgE after 28 days of treatment.
• To assess any change in morning and evening PEFR as recorded by the PIKO meters longitudinally over 28 days of treatment.
• To assess the effect of QAV680 on asthma control using weekly Asthma Control
Questionnaire (ACQ) scores over 28 days of treatment.
• To assess the extent of inhaled salbutamol use as rescue medication over 28 days of treatment.
Exploratory objective:
• To assess if post bronchodilator FEV1 measurements demonstrate any potential additive effects on top of the bronchodilator response compared to Baseline. | |
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives | Part of the same protocol (exporatory objective) but separate consent :
• To investigate exploratory pharmacogenetics including how pharmacogenetics of CRTh2 SNPs affects drug response to QAV680 in patients who agree to participate in exploratory biomarker evaluation.
| |
| E.3 | Principal inclusion criteria | 1. Healthy male and female asthma patients 18 to 65 years of age included.
2. Patients with atopic moderate persistent asthma, diagnosed according to GINA
guidelines 2008 (see protocol for full details)
• atopic as confirmed by a positive skin prick test at screening to allergen
• gradually tapered down on inhaled steroids for at least 28 days
or washed off any other asthma medication before randomization. Patients may be allowed to enter the study on a stable fraction of the original dose of steroids if they meet all other inclusion criteria. Use of short-acting β2-agonists is permissible as rescue medication.
• FEV1 of ≥ 60% and ≤ 90% of the predicted normal value at Baseline after the placebo run-in period are completed
• increase of ≥12% AND 200mL in FEV1 over pre-bronchodilator value within 30 minutes after inhaling 400μg of Salbutamol MDI (or equivalent dose): reversibility
• symptomatic everyday at Baseline (after steroid and/or LABA Washout)
3. Women must be post menopausal or surgically sterilized at the time of participation (see protocol for full details).
4. Male patients must be using a two acceptable methods of contraception, (e.g.,
spermicidal gel plus condom) for the entire duration of the study, up to the Study
Completion visit, and refrain from fathering a child in the three months following the
last study drug administration. Periodic abstinence and withdrawal are not acceptable methods of contraception.
5. Patients must weigh at least 45 kg to participate in the study, and must have a body mass index (BMI) of >20 kg/m2.
6. Able to communicate well with the Investigator, to understand and comply with the requirements of the study. Understand and sign the written informed consent. | |
| E.4 | Principal exclusion criteria | 1. Pregnant or lactating women.
2. Smokers (history of smoking in previous 6 months or more than 10 pack years)
3. Use of any prescription drugs, herbal supplements, within 28 days prior to initial
dosing, and/or over-the-counter (OTC) medication, dietary supplements (vitamins
included) within 14 days prior to initial dosing other than short acting inhaled beta-agonists and paracetamol for the treatment of minor ailments e.g. headache from 48hr before the first dose until the end of study visit is acceptable, but must be documented in the Concomitant medications / Significant non-drug therapies page of the CRF.
4. Participation in any clinical investigation within 28 days prior to initial dosing, or
within 10 times the corresponding half-life of the drug taken whichever is longer.
5. Donation or loss of 400ml or more of blood within 56 days prior to initial dosing, or
longer if required by local regulation. Haemoglobin levels below normal range at
screening.
6. Significant illness within 14 days prior to initial dosing.
7. A past medical history of clinically significant ECG abnormalities, or recent history of
autonomic dysfunction (e.g., recurrent episodes of fainting, palpitations, etc).
8. History of life-threatening asthma, defined as an asthma episode that required
intubation and/or was associated with hypercapnoea, respiratory arrest and/or hypoxic seizures. History of asthma exacerbation in the past 6 months that required
hospitalization or emergency unit visit.
9. Use of a biologic (e.g., monoclonal antibodies) agent or oral corticosteroids for the
treatment of asthma in the past 4 months.
10. Any disease or illness, other than asthma, that may require the use of systemic
corticosteroids during the study period.
11. Any occupational exposure to allergens/ irritants that may have a potential to worsen the asthma symptoms during the study.
12. Respiratory tract infection and/or exacerbation of asthma within 28 days prior to the first dose of study medication. Patients with other serious underlying diseases (i.e. tuberculosis, bronchiectasis, pulmonary fibrosis, pulmonary hypertension, emphysema, chronic bronchitis, α-1-antitrypsin deficiency).
---REFER TO STUDY PROTOCOL FOR FULL LIST OF EXCLUSION CRITERIA--- | |
| E.5 End points |
| E.5.1 | Primary end point(s) | | trough FEV1 of a 28 day administration of QAV680 500mg q.i.d compared to placebo | |
| 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 | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| 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) | 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 | Information not present in EudraCT |
| 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 | No |
| 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 | |
| E.8.7 | Trial has a data monitoring committee | No |
| 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 | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
