E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) |
|
E.1.1.1 | Medical condition in easily understood language |
Chronic Obstructive Pulmonary Disease (COPD) |
|
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 | LLT |
E.1.2 | Classification code | 10010952 |
E.1.2 | Term | COPD |
E.1.2 | System Organ Class | 100000004855 |
|
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 tezepelumab SC Q4W as compared with placebo on COPD exacerbations in adults with moderate to very severe COPD |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the effect of tezepelumab SC Q4W compared with placebo on: 1. Time to first moderate or severe exacerbation. 2. Severe COPD exacerbations. 3. Pre-bronchodilator lung function. 4. Respiratory health status/health-related quality of life. 5. Pharmacokinetics and immunogenicity; not compared with placebo. |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Evaluate the effect of tezepelumab compared with placebo on: 1. Sputum biomarkers, cell counts and microbiome 2. Pharmacodynamic (PD) markers in nasal lining and sputum cell samples. 3. Nasal lining fluid biomarkers. |
|
E.3 | Principal inclusion criteria |
1) Subjects must be between 40-80 years of age. 2) Weight ≥40 kg at screening visit. 3) History of moderate to very severe physician-diagnosed COPD for at least 12 months prior to enrolment with a post-bronchodilator FEV1 ≥20% and ≤80% of predicted normal value. 4) History of at least 2 documented moderate to severe COPD exacerbations within 2 to 52 weeks prior to enrollment. 5) CAT score of ≥15 at enrollment and day of randomization. 6) Subjects should have evidence of having been treated with triple (medium or high dose ICS/LABA/LAMA) therapy for COPD throughout the year prior to enrollment, the dose should be stable for 3 months prior to screening visit. 7) Current smoker or ex-smoker with a tobacco history of ≥10 pack-years. 8) If on allergen-specific immunotherapy, subjects must be on a maintenance dose and schedule for at least 2 months prior to screening visit. 9) If on theophylline or roflumilast, subjects must be on maintenance treatment for at least 12 months prior to screening visit and on stable dose 3 months prior to screening visit. |
|
E.4 | Principal exclusion criteria |
1) Clinically important pulmonary disease other than COPD, as judged by Investigator. 2) Current or previous asthma diagnosis. 3) Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious (including risk factors for pneumonia), endocrine, metabolic, hematological, psychiatric, or major physical impairment that is not stable. 4) Treatment with systemic corticosteroids and/or antibiotics, and/or hospitalization for a COPD exacerbation within 14 days prior to enrollment. 5) History of clinically significant infection (excluding pneumonia), acute upper or lower respiratory infection, requiring antibiotics or antiviral medication within 14 days before enrollment or randomization. 6) History of pneumonia requiring antibiotics or antiviral medication within 28 days before enrollment. 7) History of allergy or reaction to any component of tezepelumab. 8 History of anaphylaxis to any other biologic therapy. 9) History of alcohol or drug abuse within the past year. 10) History of cancer. 11) Subjects with tuberculosis (TB) 12) Major surgery within 8 weeks prior to enrollment or planned surgical procedures requiring general anaesthesia. 13) Pregnant or breastfeeding. 14) Subjects randomized in the current or previous Tezepelumab studies. 15) The chest/lungs with pathology that precludes the patient’s ability to complete the study. 16) The patient has active COVID 19 infection during screening period. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1) Rate of moderate or severe COPD exacerbations. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Rate ratio of moderate or severe COPD exacerbation vs placebo over 52 weeks. |
|
E.5.2 | Secondary end point(s) |
Secondary Endpoints: 1) Time to first moderate or severe COPD exacerbation. 2) Rate of severe COPD exacerbations 3) Change from baseline in pre-brohchodilator (BD) forced expiratory volume in 1 second (FEV1) 4) Change from baseline in SGRQ score and CAT. Proportion of subjects achieving an MCID of 4 units or more in SGRQ total score. 5) Evaluate pharmacokinetics (serum trough concentration) and immunogenicity (incidence of anti-drug antibodies(ADA)) of tezepelumab. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Key Secondary Endpoints: 1) over 52 weeks 2) over 52 weeks 3) at week 52 4) at week 52 5) over 52 weeks |
|
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 | 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 | 30 |
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 |
Canada |
Israel |
Korea, Republic of |
United States |
France |
Netherlands |
Spain |
Germany |
Denmark |
United Kingdom |
|
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
|
Last Subject Last Visit (LSLV) |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 23 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 23 |