E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic obstructive pulmonary disease |
Krónikus obstruktív tüdőbetegség (COPD) |
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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 | 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 |
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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 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)
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A kéthetente alkalmazott dupilumab hatásosságának értékelése középsúlyos-súlyos COPD-ben szenvedő betegeknél, a következőkkel mérve: • Az akut középsúlyos vagy súlyos COPD exacerbációk egy évre vetített előfordulási aránya (AECOPD) |
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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) |
A kéthetente alkalmazott dupilumab alábbiakra kifejtett hatásának értékelése: - 1 másodpercre jutó erőltetett kilégzési térfogat (FEV1) hörgőtágító alkalmazása előtt, 12 hét során, placebóhoz hasonlítva - Egészséggel összefüggő életminőség a St. George's Respiratory Questionnaire (SGRQ) alapján a kiindulástól az 52. hétig bekövetkezett változások értékelésével - Hörgőtágító alkalmazása előtti FEV1 52 hét során, placebóhoz viszonyítva - Tüdőfunkció értékelése - Középsúlyos és súlyos COPD exacerbációk - Biztonságosság és tolerálhatóság értékelése - A dupilumab szisztémás jelenlétének és a dupilumab ellenanyag (ADA) megjelenésének követése |
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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: - Current or former smokers with a smoking history of ≥10 pack-years. - Moderate-to-severe COPD (post-bronchodilator FEV1/ forced vital capacity [FVC] ≤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 Visit 1. |
A következő feltételeknek megfelelő, COPD-re vonatkozó orvosi diagnózissal rendelkező betegek: - Jelenleg vagy korábban dohányzó egyén ≥10 pack-year index-szel - Közepesen súlyos – súlyos COPD (hörgőtágító alkalmazása után mért FEV1 ill. erőltetett itálkapacitás [FVC] aránya ≤70% és a hörgőtágító alkalmazása után mért 1 másodpercre jutó erőltetett kilégzési térfogat százalékban (%) kifejezett értéke (FEV1 %) az elvárt értéknek a >30% és ≤70% közötti tartományában van). - Medical Research Council (MRC) skála érték ≥2. - A beteg közlése alapján a krónikus bronchitis jelei és tünetei (krónikus produktív köhögés) a szűrést megelőző egy évben, 3 hónapon keresztül, a krónikus köhögés egyéb ismert okának hiányában. - Magas exacerbációs rizikóra utaló kórtörténet: a beválasztást megelőző 1 évben ≥2 közepesen súlyos exacerbáció vagy ≥1 súlyos exacerbáció. A közepesen súlyos exacerbáció vizsgáló által rögzített, s akut COPD-s exacerbációnak (AECOPD) minősül és szisztémás kortikoszteroid (i.m., i.v., p.o.) és/vagy antibiotikum kezelést igényelt. A két elvárt exacerbációs jelenségből legalább az egyik kortikoszteroid kezelést igényelt. A súlyos exacerbáció orvos által diagnosztizált, s AECOPD-nek minősül és kórházi vagy sürgősségi ellátást igényelt. - Hármas terápiás előzmény (inhalációs kortikoszteroid [ICS] + hosszú hatású béta agonista [LABA] + hosszú hatású muszkarin agonista [LAMA]) a randomizációt megelőző 3 hónapban, stabil gyógyszer dózis alkalmazásával az 1. vizitet megelőző 1 hónapban; amennyiben az ICS kontraindikált, kettős terápia (LABA + LAMA) megengedett. - Bizonyítottan fennálló 2-es típusú gyulladás: 1. viziten a beteg eozinofil értéke > 300 eozinofil sejt/mikroliter. |
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E.4 | Principal exclusion criteria |
- COPD diagnosis for less than 12 months prior to randomization. - A current diagnosis of asthma or history of asthma according to the 2018 Global Initiative for Asthma (GINA) guidelines or other accepted guidelines. - 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. - Treatment with oxygen of more than 12 hours per day. - 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. |
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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 |
A középsúlyos vagy súlyos COPD exacerbációk egy évre vetített előfordulási aránya az 52 hetes kezelési időszak során, placebóhoz hasonlítva. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline to week 52 |
Alapértéktől az 52. hétig |
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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 48 ; Change in pre-bronchodilator FEV1 from baseline to weeks other than 12 and 52 (i.e. Weeks 2, 4, 8, 16, 20, 24, 28, 36, 44 and 48) 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, 16, 24, 28, 36, 44 and 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 |
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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, 16, 20, 24, 28, 36, 44, 48 6 : Baseline to weeks 2, 4, 8, 12, 24, 36, 52 7 : Baseline to weeks 2, 4, 8, 12, 16, 24, 28, 36, 44, 52 10, 11, 12 : Baseline through week 64 |
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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 | 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
| Information not present in EudraCT |
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 | 121 |
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 |
Belgium |
Brazil |
Bulgaria |
Canada |
Chile |
Colombia |
Czech Republic |
France |
Germany |
Greece |
Hungary |
Latvia |
Lithuania |
Mexico |
Netherlands |
Peru |
Poland |
Portugal |
Romania |
Russian Federation |
Serbia |
Slovakia |
South Africa |
Spain |
Ukraine |
United Kingdom |
United States |
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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
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LVLS |
Utolsó beteg utolsó vizit |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |