E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Obstructive Pulmonary Disease (COPD) |
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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 | 10010952 |
E.1.2 | Term | COPD |
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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 assess the ability of IMD-1041 to reduce levels of selected systemic and induced sputum biomarkers in patients with COPD |
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E.2.2 | Secondary objectives of the trial |
• To evaluate change in lung function in patients with COPD following oral dosing of IMD-1041
• To determine the safety and tolerability of IMD-1041 following oral dosing in patients with COPD |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males and non-pregnant, non-lactating females aged ≥40 and ≤80 years of age at the time of the screening visit. (Women of childbearing potential will be allowed to enter the trial only if they are using one medically approved i.e., mechanical or pharmacological) contraceptive measure. A female is considered to be of childbearing potential unless she has had an hysterectomy, is at least one year post-menopausal, or has undergone tubal ligation. All women of childbearing potential must have a negative pregnancy test at screening visit and week 12 (Visit 3)
2. Patients with a clinical diagnosis of COPD, grade 2 or 3 according to the GOLD guidelines 2007 and stable airway obstruction
3. Patients with a post-salbutamol FEV1 > 30% of the predicted value, < 80% of the predicted value (i.e., 30% ≤ 100 x observed post-salbutamol FEV1/ predicted FEV1 <80%) or who is deemed suitable by the Investigator (at either screening or baseline)
4. Post-salbutamol FEV1/forced vital capacity (FVC) <70% (i.e,. 100 x post-salbutamol FEV1/FVC <70%) (at either screening or baseline)
5. Current, or ex-cigarette smokers with a smoking history of at least 10 pack-years. Pack-years will be calculated by dividing the number of cigarettes smoked per day by 20 (the number of cigarettes in a pack) and multiplying this figure by the number of years a person had smoked. For example, a person who smokes 40 cigarettes a day and has smoked for 10 years would have a 20 pack-year smoking history (40 cigarettes per day ÷ 20 cigarettes per pack = 2; 2 x 10 years of smoking = 20 pack-year history)
6. Patients who have the ability to produce a viable sputum sample (< 50% squamous cells)
7. Predominant current diagnosis of smoking related COPD
8. Patients who were eligible and able to participate in the trial and who consented to do so in writing after the purpose and nature of the investigation had been explained to them |
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E.4 | Principal exclusion criteria |
1. History or current diagnosis of asthma, allergic rhinitis or atopy. N.B. Misdiagnosed asthma or childhood asthma is acceptable, however must be confirmed by the Investigator
2. Eosinophil count >600 cells/mm3
3. A respiratory tract infection (including the upper respiratory tract) or COPD exacerbation in the 6 weeks prior to the screening visit
4. Patients who have been hospitalised for an acute COPD exacerbation in the 12 months or an exacerbation in the last 3 months which was treated with oral steroids prior to the screening visit
5. Use of long-term oxygen therapy (≥15 hours/day)
6. Clinically significant respiratory conditions defined as: • Known active tuberculosis • History of interstitial lung or pulmonary thromboembolic disease • Pulmonary resection during the past 12 months • History of life-threatening COPD • History of bronchiectasis secondary to respiratory diseases other than COPD (e.g., cystic fibrosis, Kartagener’s syndrome, etc) • Patients who in the Investigator’s opinion may need pulmonary rehabilitation or a thoracotomy during the trial
7. Clinically significant cardiovascular conditions defined as: • Myocardial infarction during the last 6 months • Unstable arrhythmia which required changes in the pharmacological therapy or other intervention during the last 12 months, or newly diagnosed arrhythmia within the previous 3 months • Hospitalisation within the previous 12 months for heart failure functional classes III (marked limitation of activity and only comfortable at rest) and IV (need of complete rest, confinement to bed or chair, discomfort at any physical activity and presence of symptoms at rest) as per the New York Heart Association
8. Patients with any other serious or uncontrolled physical or mental dysfunction at the discretion of the Investigator, which could place the patient at higher risk derived from his/her participation in the study, could confound the results of the trial, or is likely to prevent the patient from complying with the requirements of the trial or completing the trial period
9. Patients who are not able to perform reproducible spirometry attempts at the screening visit or during the repeat at baseline
10. Clinically relevant abnormalities in the results of laboratory, ECG parameters (QTc > 470 milliseconds), or physical examination at the screening evaluation if the abnormality defines a disease state listed as an exclusion criterion, except for those related to COPD
11. Patients with a history of drug and/or alcohol abuse that may prevent compliance with trial activities
12. Treatment with any IMP within 3 month prior to screening visit
13. Changes to any concomitant therapy either for COPD or any other well-controlled illness within 1 month prior to screening visit
14. Treatment with a prohibited medication as detailed in Section 5.8 Any further issues regarding the eligibility of a particular patient for entry into the trial will be discussed between the Investigator and the Sponsor or its representatives and will be documented accordingly |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary end-points: • IL-1β, IL-6, TNF-α and GRO-α in blood and/or induced sputum • Total and differential white cell count in induced sputum
Secondary end-points: • Safety and tolerability • CCL5, IL-8, MMP9, TIMP1, MCP-1 and MPO in induced sputum and/or blood • PAI-1 in induced sputum and PAI-1 and t-PA-PAI complex in blood • Lung function assessments |
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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 | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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
| 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 | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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 | Information not present in EudraCT |
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 | 5 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |