E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010952 |
E.1.2 | Term | COPD |
E.1.2 | System Organ Class | 100000004855 |
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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 effect of CHF 6001 on biomarkers of inflammation in induced sputum |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of CHF 6001 on biomarkers of inflammation in blood, on pulmonary function and on symptoms benefits in comparison with placebo
To evaluate the safety and tolerability of CHF 6001
To assess the pharmacokinetics profile of CHF 6001 and its metabolites
at steady state in subjects with moderate, severe COPD. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female aged ≥ 40 years
2. A female is eligible to enter the study if she is of non-childbearing potential i.e. physiologically incapable of becoming pregnant
3. Subjects with an established diagnosis of COPD (according to GOLD guidelines, update 2015) at least 12 months prior to the screening visit
4. With a smoking history of at least 10 pack-years [pack-years=number of cigarettes per day x number of years/20]. Current and ex- smokers are eligible. (Smoking cessation must be at least 3 months prior to the screening.
5. With a BMI in the range of 18-35 Kg/m2
6. With a post- bronchodilator FEV1 ≥ 30% and ≤ 70% of the subject normal predicted value and a post-bronchodilator FEV1/FVC ratio <0.70 measured 10-15 minutes after 400µg (4 puffs x 100µg) of salbutamol pMDI. If this criterion is not met at screening, the test can be repeated once before randomisation visit.
7. Subjects must be receiving daily maintenance with triple therapy (ICS plus LABA plus LAMA) at stable dose and dosing regimen, for at least 2 months prior to screening
8. With a history of chronic bronchitis defined as chronic cough and sputum production for more than three months per year for two or more years and known as ‘spontaneous sputum producer’ subject
9. At screening, subjects must be able to produce an adequate induced sputum sample defined as a load of at least 300 mg with a viability factor of not less than 70% (with less than 30% epithelial cells) and a neutrophil % differential count of at least 60%.
10. Subjects must be symptomatic at screening defined as having a CAT score ≥10
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E.4 | Principal exclusion criteria |
1. Pregnant or lactating female subject
2. Subjects with a current diagnosis of asthma
3. Subjects with a moderate or severe COPD exacerbation [i.e. resulting in the use of systemic (oral/IV/IM corticosteroids) and/or antibiotics or in hospitalisation] or a lower respiratory tract infection within 6 weeks prior to study entry or during the screening period
4. Subjects on maintenance bronchodilators therapy only (LABA alone, LAMA alone, dual LABA/LAMA alone) or maintenance dual therapy only (ICS/LABA or ICS plus LAMA) within 2 months prior to study entry
5. Subjects on PDE4 inhibitors (e.g. roflumilast) within 2 months prior to study entry
6. Subjects requiring long-term (at least 12 hours daily) oxygen therapy for chronic hypoxemia
7. Subjects participating to a pulmonary rehabilitation programme or completing such a programme within the last 6 weeks prior to study entry
8. Subjects with known respiratory disorders other than COPD that in investigator’s opinion would affect efficacy and safety evaluation or place the subject at risk. This can include but is not limited to known alpha-1 antitrypsin deficiency, active tuberculosis, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension and interstitial lung disease
9. Subjects with active (lung) cancer or a history of lung cancer ;or a history of cancer other than lung cancer with less than 5 years disease free survival time (whether or not there is evidence of local recurrence or metastases). Localized carcinoma (e.g. basal cell carcinoma (without metastases), in situ carcinoma of the cervix adequately treated,) is acceptable
10. Subjects with a known history of hypersensitivity to β2-agonist, PDE4 inhibitors or any of the excipients contained in any of the formulations used in the trial
11. Subjects who have known history of clinically significant cardiovascular conditions such as, but not limited to, unstable or acute ischemic heart disease within one year prior to study entry, NYHA Class III/IV heart failure, known history of sustained and non-sustained cardiac arrhythmias or history of atrial fibrillation diagnosed in the last 6 months prior to study entry and not controlled with therapy rate control strategy as well as subjects with a history or symptoms of significant neurological disease including transient ischemic attack (TIA), stroke, seizure disorder or behavioural disturbances
12. Male subjects with a QTcF >450 ms and female subjects with a QTcF >470 ms at screening and/or at randomisation visits
13. Subjects who have unstable concurrent disease: e.g. uncontrolled hyperthyroidism, uncontrolled diabetes mellitus or other endocrine disease; significant hepatic impairment, significant renal impairment; history of cerebrovascular disease; uncontrolled gastrointestinal disease (e.g. active peptic ulcer, Crohn’s disease, ulcerative colitis, enteritis, unexplained diarrhea, bloody or loose stools); uncontrolled haematological disease; uncontrolled autoimmune disorders (e.g. rheumatoid arthritis, inflammatory bowel disease) or other disease or condition that might, in the judgement of the investigator , place the subject at undue risk or potentially compromise the results or interpretation of the study
14. Subjects with abnormal alanine aminotransferase (ALT) ≥2x upper limit of normal (ULN) and/ or aspartate aminotransferase (AST) ≥2x ULN and/or bilirubin ≥1.5x ULN. Isolated bilirubin ≥1.5x ULN is acceptable if fractionated and direct bilirubin is <35%
15. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones)
16. Subjects receiving treatment with any drug known to have a well-defined potential for hepatotoxicity (e.g. isoniazide, nimesulide, ketoconazole) within the previous 3 months prior to the study entry
17. Subjects have experienced excessive weight loss recently (which cannot be explained by the natural course of COPD or known background conditions).
18. Subjects with a history of alcohol abuse and/or substance/drug abuse within 12 months prior to screening visit
19. Subjects having received any other investigational drug within the preceding 30 days (60 days for biologics), or a longer and more appropriate time as determined by the Investigator (e.g., approximately five half-lives of the previous investigational drug).
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E.5 End points |
E.5.1 | Primary end point(s) |
sputum cell count and biomarkers
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
on Day 32 at steady state |
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E.5.2 | Secondary end point(s) |
1/ blood biomarkers
2/ lung function,
3/ TDI, CAT scores
4/ PK parameters
5/ Safety (AEs, ADRs, vital signs)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
on day 32, except for AE ADR |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
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 | No |
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 | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
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 | 2 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
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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 | 9 |
E.8.9.1 | In the Member State concerned days | |