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 |
|
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 | 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 evaluate the efficacy of dupilumab administered every 2 weeks in patients with moderate or severe Chronic Obstructive Pulmonary Disease (COPD) as measured by
- Annualized rate of acute moderate or severe COPD exacerbation (AECOPD)
|
|
E.2.2 | Secondary objectives of the trial |
To evaluate the effect of dupilumab administered every 2 weeks on
- Pre-bronchodilator forced expiratory volume in 1 second (FEV1) over 12 weeks compared to placebo
- Health related quality of life, assessed by the change from baseline to Week 52 in the St. George’s Respiratory Questionnaire (SGRQ)
- Pre-bronchodilator FEV1 over 52 weeks compared to placebo
- Lung function assessments
- Moderate and severe COPD exacerbations
To evaluate safety and tolerability
To evaluate dupilumab systemic exposure and incidence of antidrug antibodies (ADA) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Participants with a physician diagnosis of COPD who meet the following criteria at screening:
* Current or former smokers with a smoking history of ≥10 pack-years.
* Moderate-to-severe COPD (post-bronchodilator FEV1/ forced vital capacity [FVC] ratio <0.70 and post-bronchodilator FEV1 % predicted >30% and ≤70%).
* Medical Research Council (MRC) Dyspnea Scale grade ≥2.
* Patient-reported history of signs and symptoms of chronic bronchitis (chronic productive cough) for 3 months in the year up to screening in the absence of other known causes of chronic cough.
* Documented history of high exacerbation risk defined as exacerbation history of ≥2 moderate or ≥1 severe within the year prior to inclusion. At least one exacerbation should have occurred while the patient was taking inhaled corticosteroid (ICS)/long acting beta agonist (LABA)/long acting muscarinic antagonist (LAMA) (or LABA/LAMA if ICS is contraindicated). Moderate exacerbations are recorded by the investigator and defined as AECOPD that require either systemic corticosteroids (intramuscular, intravenous, or oral) and/or antibiotics. One of the two required moderate exacerbations has to require the use of systemic corticosteroids. Severe exacerbations are recorded by the investigator and defined as AECOPD requiring hospitalization or observation > 24 hours in emergency department/urgent care facility.
* Background triple therapy (ICS + LABA + LAMA) for 3 months prior to randomization with a stable dose of medication for ≥1 month prior to Visit 1; Double therapy (LABA + LAMA) allowed if ICS is contraindicated.
- Evidence of Type 2 inflammation: Patients with blood eosinophils ≥300 cells/microliter at Vis |
|
E.4 | Principal exclusion criteria |
- COPD diagnosis for less than 12 months prior to randomization.
- Participants with current diagnosis of asthma according to the Global Initiative for Asthma (GINA) guidelines, or documented history of asthma.
- Significant pulmonary disease other than COPD (e.g., lung fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension, bronchiectasis, Churg-Strauss Syndrome etc) or another diagnosed pulmonary or systemic disease associated with elevated peripheral eosinophil counts.
- Cor pulmonale, evidence of right cardiac failure.
- Long-term treatment with oxygen >4.0 L/min OR if a participant requires more than 2.0 L/min in order to maintain oxygen saturation >88%
- Hypercapnia requiring Bi-level ventilation.
- AECOPD as defined in inclusion criteria within 4 weeks prior to screening, or during the screening period.
- Respiratory tract infection within 4 weeks prior to screening, or during the screening period.
- History of, or planned pneumonectomy or lung volume reduction surgery. Patients who are participating in the acute phase of a pulmonary rehabilitation program, ie, who started rehabilitation <4 weeks prior to screening (Note: patients in the maintenance phase of a rehabilitation program can be included).
- Diagnosis of α-1 anti-trypsin deficiency. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Annual rate of acute COPD exacerbation (AECOPD) ; Annualized rate of moderate or severe COPD exacerbations over the 52-week treatment period compared to placebo |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1 - Change in pre-bronchodilator FEV1 ; Change in pre-bronchodilator FEV1 from baseline to Week 12 compared to placebo
2 - Change in SGRQ ; Change from baseline to Week 52 in SGRQ total score compared to placebo
3 - Improvement in SGRQ ; Proportion of patients with SGRQ improvement ≥4 points at Week 52
4 - Change in pre-bronchodilator FEV1 from baseline to Week 52 ; Change in pre-bronchodilator FEV1 from baseline to Week 52 compared to placebo
5 - Change in pre-bronchodilator FEV1 from baseline to time points up to Week 44 ; Change in pre-bronchodilator FEV1 from baseline to weeks other than 12 and 52 (i.e. Weeks 2, 4, 8, 24, 36, and 44) compared to placebo
6 - Change in post-bronchodilator FEV1 lung function ; Change in post-bronchodilator FEV1 from baseline at Weeks 2, 4, 8, 12, 24, 36 and 52 compared to placebo
7 - Change in forced expiratory flow (FEF) 25-75% ; Change in FEF 25-75% from baseline to Weeks 2, 4, 8, 12, 24, 36, 44, 52
8 - Annualized rate of severe AECOPD ; Annualized rate of severe COPD exacerbations compared to placebo over the 52-week treatment period
9 - Time to first AECOPD ; Time to first moderate or severe COPD exacerbation compared with placebo during the 52-week treatment period
10 - Adverse events ; Number of adverse events (AEs)/treatment-emergent adverse events (TEAEs)
11 - Potentially clinically significant abnormality (PCSA) in laboratory tests ; Percentage of patients with at least one incidence of PCSA
12 - Anti-drug antibodies ; Incidence of anti-drug antibodies against dupilumab |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 : Baseline to week 12
2, 3, 4, 8, 9 : Baseline to week 52
5 : Baseline to weeks 2, 4, 8, 24, 36, 44
6 : Baseline to weeks 2, 4, 8, 12, 24, 36, 52
7 : Baseline to weeks 2, 4, 8, 12, 24, 36, 44, 52
10, 11, 12 : Baseline through week 64 |
|
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 | 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) | 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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 130 |
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 |
Brazil |
Canada |
Chile |
Colombia |
Mexico |
Peru |
Russian Federation |
Serbia |
South Africa |
Ukraine |
United States |
Belgium |
Czechia |
France |
Germany |
Greece |
Hungary |
Latvia |
Lithuania |
Poland |
Portugal |
Slovakia |
United Kingdom |
Bulgaria |
Netherlands |
Romania |
Spain |
|
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 | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |