| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic Obstructive Pulmonary Disease (COPD) and Chronic Bronchitis |
|
| E.1.1.1 | Medical condition in easily understood language |
| Chronic Obstructive Pulmonary Disease (COPD) |
|
| 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 | 10010952 |
| E.1.2 | Term | COPD |
| E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
| 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 evaluate the efficacy of two doses of CHF6001 add-on to maintenance triple therapy (free or fixed combination of ICS, LABA, LAMA) to reduce the rate of moderate and severe exacerbations after 52 weeks of treatment in comparison with maintenance triple therapy (i.e. placebo arm). |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate
- the efficacy of the two doses of CHF6001 add-on to maintenance triple therapy on health-related quality of life after 52 weeks of treatment (change in SGRQ total score).
-the efficacy of the two doses of CHF6001 add-on to maintenance triple therapy on lung function, health-related quality of life, severe exacerbations in the pooled analysis of CLI-06001AA1-04 Main cohort (excluding subjects enrolled in China) and CLI-06001AA1-05 studies and other clinical outcome measures in comparison with maintenance triple therapy
-the safety and tolerability of the two doses of CHF6001
-the efficacy, safety and tolerability of the two doses of CHF6001 in comparison with Roflumilast.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Males and females aged ≥ 40 years with written informed consent obtained prior to any study related procedure;
2.Females are eligible to enter the study if they are of
a/non- childbearing potential
b/childbearing potential, they must have a negative pregnancy test at screening and must agree to use one or more of the acceptable contraceptive measures.
3.Subjects with an established diagnosis of COPD with chronic bronchitis
4. Current smokers or ex-smokers who quit smoking at least 6 months prior to screening visit, with a smoking history of at least 10 pack years
5. A post-bronchodilator FEV1 < 50% of the patient predicted normal value and a postbronchodilator FEV1/FVC ratio < 0.7 after 400μg (4 puffs x 100μg) of salbutamol pMDI or equivalent dose of albuterol pMDI in the US
6. A documented history (e.g. medical record verification) of at least one moderate or severe COPD exacerbation in the previous year.
7.Symptomatic subject at screening defined as having a CAT score ≥10.
8. Subjects prescribed with maintenance triple therapy (free or fixed combination of ICS, LABA,LAMA) according to GOLD 2020 recommendations, for at least 12 months prior to screening and
receiving regular maintenance triple therapy for at least 3 months prior to the screening visit. ICS must be in an approved dose for COPD.
9. Subjects are willing and able to be trained to use correctly the DPI inhalers (NEXThaler®).
10. Subjects are willing and able to be trained to use correctly the electronic devices with COPD questionnaires, to understand and to perform required outcome measurements of the protocol (e.g.spirometry maneuvers etc.) and ability to understand the risks involved. |
|
| E.4 | Principal exclusion criteria |
1.Subjects with a diagnosis of current asthma.
2. Subjects with a moderate or severe COPD exacerbation 4 weeks prior to study entry and during run-in period.
3. Pregnant and lactating women.
4. Subjects requiring long term (at least 15 hours daily) oxygen therapy for chronic hypoxemia.
5. Subjects with known α-1 antitrypsin deficiency as the underlying cause of COPD.
6. Subjects with primary diagnosis of emphysema not related to COPD.
7.Subjects with clinically significant respiratory disorders other than COPD.
8. Subjects with lung volume reduction surgery.
9. Subjects having lung cancer or a history of lung cancer fully recovery less than 1 year after completing cancer therapy.
10. Subjects with active cancer or a history of cancer (other than the lung) fully recovery less than 1 year after completing cancer therapy or any untreated localized carcinoma
11. Subjects with a history of allergy or hypersensitivity to anticholinergics, β2-agonists,corticosteroids, PDE-4 inhibitors or any of the excipients contained in any of the formulations used in the trial or a medical condition such as narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that in the investigator’s opinion would contra-indicate study participation.
12.Subjects under Roflumilast treatment within 6 months before study entry.
13. Subjects with a diagnosis of depression, generalized anxiety disorder, suicidal ideation or behavior that might, according to the investigator judgement, place the patient at undue risk.
14.Subjects who have clinically significant cardiovascular condition.
15.An abnormal and clinically significant 12-lead ECG finding in relation to the subject’s medical history that results in active medical problem which may impact the safety of the patient according to investigator’s judgement.
16.Subjects with a significant neurological disease including transient ischemic attack (TIA), stroke, seizure disorder or behavioural disturbances that in investigator’s opinion, would place the patient at risk by participating to the study.
For complete list of exclusion criteria, please refer to the protocol.
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|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Annual rate of moderate and severe exacerbations over 52 weeks |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
•Change from baseline in SGRQ Total score at week 52
•Time to first moderate/severe exacerbation
•Annual rate of severe exacerbations
•Time to first severe exacerbation
•Change from baseline in morning pre-dose of FEV1 at week 52
•Change from baseline in SGRQ Domain scores at week 52
•SGRQ response (i.e., change from baseline in SGRQ score ≥ -4) at week 52
•Change from baseline to last inter-visit period (week 40-52) in the average E-RS total and sub-scale scores
•E-RS response (i.e., change from baseline in E-RS total score ≤ -2) at week 52
•Change from baseline to last inter-visit period (week 40-52) in the percentage of days without intake of rescue medication and in the average daily use of rescue medication (number of puffs)
•Time to study medication discontinuation due to any reason
•Time to first moderate or severe exacerbation or study medication discontinuation (due to any / or class related adverse events, lack of efficacy or death (composite endpoint) and time to its individual components (i.e. time to study medication discontinuation).
|
|
| 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 | 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 | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | Yes |
| 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 | 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) | Yes |
| 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 | 19 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 151 |
| 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 |
| Chile |
| New Zealand |
| Bosnia and Herzegovina |
| Ukraine |
| Israel |
| Mexico |
| Russian Federation |
| South Africa |
| United Kingdom |
| United States |
| Austria |
| Bulgaria |
| Croatia |
| Czechia |
| Estonia |
| Germany |
| Greece |
| Hungary |
| Latvia |
| Netherlands |
| Poland |
| Romania |
| Slovakia |
| Spain |
| Türkiye |
|
| 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 | 4 |
| E.8.9.1 | In the Member State concerned months | 1 |
| E.8.9.1 | In the Member State concerned days | 3 |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
| E.8.9.2 | In all countries concerned by the trial days | 3 |
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