| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Severe Eosinophilic Asthma |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10068462 |
| E.1.2 | Term | Eosinophilic asthma |
| E.1.2 | System Organ Class | 100000004855 |
|
| 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 demonstrate the efficacy of at least one dose of CHF 6532 on moderate and severe asthma exacerbations rate compared to Placebo arm over 52 weeks of treatment. |
|
| E.2.2 | Secondary objectives of the trial |
- To assess the effect of CHF 6532 on severe asthma exacerbations compared to Placebo over 52 weeks of treatment.
- To assess the effect of CHF 6532 compared to Placebo in terms of change from baseline in pre-dose morning forced expiratory volume in the first second (FEV1) at Week 52.
- To perform a population PK analysis investigating the inter-subject variability in the drug exposure and the effect of selected covariates on PK.
- To assess the effect of CHF 6532 compared to Placebo in terms of change from baseline on SGRQ, ACQ-5, AQLQ+12, at Week 52.
- To collect data in order to assess the impact of study treatments on health economics outcome.
- To assess the safety and the tolerability of the study treatments with respect to adverse events, electrocardiograms (ECGs), Vital Signs and Laboratory tests. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Informed consent: Subjects’ written informed consent or Adolescents legal representative’s informed consent obtained prior to any study-related procedures.
2.Gender & Age: Male or female subjects aged ≥12 years and ≤75 years.
3.Asthma diagnosis: Subjects with a diagnosis of asthma (according to GINA) for a period of at least 24 months prior to screening.
4.Previous medication: Subjects treated according to GINA step 4/5:
- with stable high-dose inhaled corticosteroids (ICS) plus a long-acting β2 agonist (LABA)
- with or without long-acting muscarinic antagonist (LAMA) or alternate therapy Leukotriene Receptor Antagonist or theophylline (except asthma anti-inflammatory monoclonal antibodies (e.g. omalizumab, mepolizumab, reslizumab, etc.) or any other biologics)
- with or without Oral corticosteroid (OCS) at stable dose not above 20 mg/days eq.
if taken at stable dose for at least 4 weeks prior to screening.
5.Asthma exacerbation history
6.A positive response to a reversibility test at screening
7.Blood eosinophils level: Subjects with evidenced eosinophilic airway inflammation as reflected by a peripheral blood eosinophil count ≥250/µL blood eosinophils level at screening visit.
8.ACQ-5: Subjects with uncontrolled asthma as evidenced by an Asthma Control Questionnaire © (ACQ-5) score ≥1.5 at screening and randomisation visits.
9. A co-operative attitude and ability:
-to perform all trial related procedures including technically acceptable pulmonary function tests;
-to correctly use the electronic diary/peak flow meter.
10.Ability of subjects to swallow tablets. |
|
| E.4 | Principal exclusion criteria |
1. Pregnant or lactating women and all women physiologically capable of becoming pregnant (i.e. women of childbearing potential) UNLESS are using one or more of the reliable methods of contraception
2.Run-in compliance < 50% at randomisation
3.Asthma exacerbation or Respiratory tract infection: Hospitalisation, emergency room admission or use of systemic corticosteroids for an asthma exacerbation or respiratory tract infection in the 4 weeks prior to screening visit or during the run-in period.
4.Subjects with a history of near fatal asthma or of a past hospitalisation for asthma in intensive care unit which, in the judgement of the investigator, may place the subjects at undue risk.
5.Bacterial lower respiratory tract infection: Subjects with a history of more than 2 episodes of confirmed bacterial lower respiratory tract infection within the year prior to screening or with a bacterial lower respiratory tract infection during the run-in.
6. History of diagnosis of COPD, cystic fibrosis, bronchiectasis or alpha-1 antitrypsin deficiency, or any other significant lung disease which may interfere with study evaluations.
7.ECG criterion: with a marked resting baseline prolongation of mean QTc interval
8. Subjects with a family history of long QT Syndrome.
9.Subjects with hypokalemia (serum K< 3.5 mmol/L) at screening.
10.Subjects who have known clinically significant cardiovascular conditions
11.Subjects with a history of symptoms or significant neurological disease
12.Subjects with clinically significant abnormal serum biochemistry, haematology (not associated with the study indication) at screening according to the investigators judgement.
13.Current smokers or ex-smokers with total cumulative exposure ≥10 pack-years or having stopped smoking less than one year prior to screening visit.
14.Subjects with historical or current evidence of uncontrolled concurrent disease
15.Subjects with a history of hypersensitivity and/or idiosyncrasy to any of the test compounds or excipients employed in this study.
16.Subjects receiving treatment with any drug known to have a well-defined potential for hepatotoxicity within the previous 3 months before the screening visit.
17.Subjects receiving treatment with one or more drugs listed in the prohibited medication section.
18.Regular use of oral or systemic corticosteroids for diseases other than asthma within the past 12 months or any intra-articular or short-acting, intramuscular corticosteroid within 1 month or intramuscular, long-acting depot corticosteroids within 3 months prior to screening.
19.Subjects with severe hepatitis, chronic active hepatitis or evidence of uncontrolled chronic liver disease
20.Subjects with ALT or AST at screening ≥2xULN.
21.Subjects with other severe acute or chronic medical or malignancy or psychiatric conditions which are uncontrolled or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and would make the subjects inappropriate for entry into this study.
22.Subjects with a history of lung volume resection.
23.Lung cancer or history of lung cancer: Subjects with a diagnosis of lung cancer or a history of lung cancer.
24.Cancer or history of cancer (other than lung): Subjects with active cancer or a history of cancer with less than 5 years disease free survival time (whether or not there is evidence of local recurrence or metastases). Localised carcinoma (e.g. basal cell carcinoma, in situ carcinoma of the cervix adequately treated) is acceptable.
25.Participation to investigational trial: Subjects who have received an investigational drug within 30 days (60 days for biologics) or five half-lives (whichever is greater) prior to screening visit.
26.Subjects with a history of alcohol or drug abuse within two years prior to screening visit.
27.Subjects with major surgery in the 3 months prior to screening visit or planned surgery during the trial.
28.Subjects mentally or legally incapacitated or subjects accommodated in an establishment as a result of an official or judicial order.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Rate of moderate and severe asthma exacerbation over 52 weeks of treatment |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
•Time to first moderate or severe exacerbation
•Time to first severe exacerbation
•Severe exacerbations rate over 52 weeks of treatment.
•Change from baseline in pre-dose FEV1 at Week 52
•Change from baseline in the SGRQ total score and domain scores at Week 52
•Change from baseline in ACQ-5 at Week 52
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
Health economic
Exploratory |
|
| 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 | 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.8.2.4 | Number of treatment arms in the trial | 4 |
| 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 | 14 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 145 |
| 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 |
| Argentina |
| Bulgaria |
| Chile |
| Czech Republic |
| France |
| Germany |
| Greece |
| Hungary |
| Italy |
| Poland |
| Russian Federation |
| Ukraine |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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