E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Obstructive Pulmonary Disease |
|
E.1.1.1 | Medical condition in easily understood language |
Chronic Obstructive Pulmonary Disease |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10009033 |
E.1.2 | Term | Chronic obstructive pulmonary disease |
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 investigate effects of SAR440340 (anti-interleukin-33 [IL33] monoclonal antibody [mAb]) compared with placebo, on the annualized rate of moderate*-to-severe** acute exacerbations of COPD (AECOPD) over up to 52 weeks of treatment.
- Moderate exacerbations are recorded by the Investigator and defined as AECOPD that require either systemic corticosteroids (such as intramuscular, intravenous or oral) and/or antibiotics.
- Severe exacerbations are recorded by the Investigator and defined as AECOPD requiring hospitalization, emergency medical care visit or resulting in death. |
|
E.2.2 | Secondary objectives of the trial |
- To investigate effects of SAR440340 compared with placebo, on improving respiratory function, as assessed by prebronchodilator forced exploratory volume in 1 second (FEV1).
- To evaluate effects of SAR440340 compared with placebo, on Post-bronchodilator FEV1.
- To evaluate effects of SAR440340 compared with placebo, on duration from baseline to first moderate or severe AECOPD event
- To evaluate effects of SAR440340 compared with placebo, on safety and tolerability. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Participants with a diagnosis of Chronic Obstructive Pulmonary Disease (COPD) for at least 1 year (based on Global Initiative for Chronic Obstructive Lung Disease [GOLD] definition.
-Participants with moderate-to-severe COPD (post-bronchodilator Forced Expiratory Volume in 1 Second [FEV1]/forced vital capacity [FVC] <70% and post-bronchodilator FEV1 % predicted <80%,
but ≥30%).
-Participants with COPD Assessment Test (CAT) score ≥10 at Screening Visit 1 and Visit 2/Randomization.
-Participants with reported history of signs and symptoms of chronic bronchitis (chronic productive cough for 3 months in the year up to screening in a patient in whom other causes of chronic cough [e.g., gastroesophageal reflux, chronic rhinosinusitis, bronchiectasis] have been excluded).
-Participants with a documented history (eg. medicla record verification) of ≥2 moderate exacerbations or ≥1 severe exacerbation within the year prior to screening. A moderate exacerbation is defined as an acute exacerbation of COPD (AECOPD) requiring systemic corticosteroids (oral, intravenous, or intramuscular) and/or treatment with antibiotics (however, use of antibiotics alone does not qualify as a "moderate exacerbation" unless documentation is available that use of antibiotics was necessary for treatment of worsening symptoms of COPD). A severe exacerbation is defined as an AECOPD that required a hospitalization.
- Participants with Standard of Care background therapy, for 3 months prior to Visit 2/Randomization and at a stable dose for at least 1 month prior to the screening, including either:
-Double therapy: Long acting beta agonist (LABA) + Long acting muscarinic agnoist (LAMA) or inhaled corticosteroid (ICS) + LABA or ICS + LAMA.
or
-Triple therapy: LABA + LAMA +ICS.
- Current or former smokers with a smoking history of ≥10 packs/year. |
|
E.4 | Principal exclusion criteria |
-Concomitant severe diseases or diseases for which the use of Inhaled Corticosteroids (ICS) (e.g., active pulmonary tuberculosis, etc.) or Long Acting Beta Agonists (LABA) are contraindicated (e.g., diagnosis of a history of significant cardiovascular diseases, insulin-dependent diabetes mellitus, hyperthyroidism, thyrotoxicosis, pheochromocytoma, hypokalemia).
-Participants with Bronchial thermoplasty procedure (up to 3 years prior to Visit 1)
-Participants with Chornic Obstructive Pulmonary Disease (COPD) diagnosed within the 6 months prior to randomization.
-A current diagnosis of asthma according to the Global Initiative for Asthma (GINA) guidelines.
-Significant pulmonary disease other than COPD (e.g., lung fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension, bronchiectasis, eosinophilic granulomatosis with polyangiitis, significant sleep apnea on Bilevel Positive Airway Pressure, etc) or another diagnosed pulmonary or systemic disease associated with elevated peripheral eosinophil counts.
-Diagnosis of α-1 anti-trypsin deficiency.
-Advanced COPD with need for chronic (>15 hours/day) oxygen support.
-Participant with a moderate or severe Acute Exacerbation of COPD event within 4 weeks prior to screening.
-A participant who has experienced an upper or lower respiratory tract infection within 4 weeks prior to Screening/Visit 1 or during the screening period.
-Prior history of or planned pneumonectomy or lung volume reduction surgery. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Rate of moderate-to-severe acute excaerbations in chronic obstructive pulmonary disease (AECOPD) patients: Annualized rate of moderate-to-severe AECOPD over up to 52 weeks |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Over up to 52 weeks treatment period |
|
E.5.2 | Secondary end point(s) |
1) Change in pre-brochodilator forced expiratory volume in 1 second (FEV1): Change in pre-bronchodilator FEV1 from Week 16 to Week 24
2) Time to first COPD Exacerbation: Time to first moderate or severe AECOPD.
3) Adverse Events: Monitor treatment emergent adverse events and serious adverse events
4) Change in post-bronchodilator FEV1: Change from baseline to Week 24 in FEV1 (post-bronchodilator) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Baseline to Week 16-24
2) Up to 52 weeks
3) Screening up to 72 weeks
4) Baseline to Week 24 |
|
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 | 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 | Yes |
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) | 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.8.2.4 | 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
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 |
Australia |
Canada |
Chile |
Germany |
Poland |
Russian Federation |
Turkey |
Ukraine |
United States |
|
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 | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |