Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
Chronic Obstructive Pulmonary Disease, COPD, tozorakimab, MEDI3506, exacerbations, ICS, LABA/LAMA, Biologic, Biologic Treatment
Brief summary
The purpose of this Phase III study is to evaluate the efficacy and safety of tozorakimab administered subcutaneously (SC) in adult participants with symptomatic COPD with a history of ≥ 2 moderate or ≥ 1 severe exacerbations of COPD in the 12 months prior to enrolment. Participants should be receiving optimised treatment with inhaled maintenance therapy (ICS/LABA/LAMA triple therapy, or dual therapy if triple is not considered appropriate) throughout at least the last 3 months prior to enrolment.
Interventions
DRUGPlacebo
Placebo administered subcutaneously, equivalent volume to tozorakimab throughout the study.
DRUGTozorakimab
Administered subcutaneously tozorakimab and placebo throughout the study.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
1. Participant must be ≥ 40 years of age and capable of giving signed informed consent. 2. Documented diagnosis of COPD for at least one year prior to enrolment. 3. Post BD FEV1/FVC \< 0.70 and post-BD FEV1 \>20% of predicted normal value 4. Documented history of ≥ 2 moderate or ≥ 1 severe COPD exacerbations within 12 months prior to enrolment. 5. Documented optimised inhaled dual or triple therapy for at least 3 months prior to enrolment. 6. Smoking history of ≥ 10 pack-years. 7. CAT total score ≥ 10, with each of the phlegm (sputum) and cough items with a score ≥ 2
Exclusion criteria
1. Clinically important pulmonary disease other than COPD. 2. Radiological findings suggestive of a respiratory disease other than COPD that is significantly contributing to the participant's respiratory symptoms. Radiological findings of pulmonary nodules suspicious for lung cancer, as per applicable guidances, without appropriate follow up prior to randomisation. Radiological findings suggestive of acute infection. 3. Current diagnosis of asthma, prior history of asthma, or asthma-COPD overlap. Childhood history of asthma is allowed and defined as asthma diagnosed and resolved before the age of 18 4. Any unstable disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric disorder, major physical and/or cognitive impairment that could affect safety, study findings or participants ability to complete the study. 5. COPD exacerbation, within 2 weeks prior to randomization, that was treated with systemic corticosteroids and/or antibiotics, and/or led to hospitalization. 6. Active significant infection within the 4 weeks prior to randomization, pneumonia within 6 weeks prior to randomization, or medical condition that predisposes the participant to infection. 7. Suspicion of, or confirmed, ongoing SARS-CoV-2 infection. 8. Significant COVID-19 illness within the 6 months prior to enrolment. 9. Unstable cardiovascular disorder. 10. Diagnosis of cor pulmonale, pulmonary arterial hypertension and/or right ventricular failure. 11. History of active severe inflammatory bowel disease or colitis within one year prior to enrolment, or unexplained diarrhoea within the 4 weeks prior to randomisation. 12. History of known immunodeficiency disorder, including a positive test for HIV-1 or HIV 2. 13. History of positive test or treatment for hepatitis B or hepatitis C (except for cured hepatitis C) 14. Evidence of active liver disease, including jaundice during screening. 15. Malignancy, current or within the past 5 years, except for adequately treated non-invasive basal cell and squamous cell carcinoma of the skin and cervical carcinoma-in-situ treated with apparent success more than one year prior to enrolment. Suspected malignancy or undefined neoplasms. 16. Participants who have evidence of active TB. 17. History of partial or total lung resection. 18. Scheduled major surgical procedure during the course of the study. 19. Participants that have previously received tozorakimab. 20. Any clinically significant abnormal findings in physical examination, vital signs, ECG, or laboratory testing during the screening period, which in the opinion of the investigator may put the participant at risk because of their participation in the study, or may influence the results of the study, or the participant's ability to complete the entire duration of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualized rate of moderate to severe COPD exacerbations in participants who are former smokers. | Over 52 weeks | The primary endpoint will be assessed in the primary population (former smokers with symptomatic COPD and a history of exacerbations, on optimised treatment with maintenance inhaled therapy \[triple therapy, or dual therapy if triple is not considered appropriate\]). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Annualized rate of moderate to severe COPD exacerbations in former or current smokers. | Over 52 weeks | The annualized rate will be assessed in the overall population of participants including current and former smokers with symptomatic COPD and history of exacerbations, on optimised treatment with maintenance inhaled therapy. |
| Change from baseline in SGRQ total score from in former smokers | Over 52 weeks | Difference in mean change from baseline in SGRQ total score in former smokers. |
| Change from baseline in SGRQ total score from in the overall population of current and former smokers. | Over 52 weeks | Difference in mean change from baseline in SGRQ total score in the overall population of current and former smokers. |
| Annualized rate of severe COPD exacerbations in former smokers | Variable duration period up to study completion, approximately 3 years | The rate ratio of severe COPD exacerbations will be assessed in former smokers. |
| Annualized rate of severe COPD exacerbations in former or current smokers | Variable duration period up to study completion, approximately 3 years | The rate ratio of severe COPD exacerbations will be assessed in the overall population of current and former smokers. |
| Change from baseline in E-RS:COPD total score in former smokers | Over 52 weeks | Difference in mean change in E-RS:COPD total score from baseline in former smokers. |
| Change from baseline in E-RS:COPD total score in former or current smokers | Over 52 weeks | Difference in mean change in E-RS:COPD total score from baseline in the overall population of current and former smokers. |
| Change from baseline in pre-bronchodilator, pre dose trough FEV1 (mL) in former smokers | Over 52 weeks | Change from baseline in pre-bronchodilator, pre dose trough FEV1 (mL) in former smokers. |
| Change from baseline in pre-bronchodilator, pre dose trough FEV1 (mL) in former or current smokers | Over 52 weeks | Change from baseline in pre-bronchodilator, pre dose trough FEV1 (mL) in the overall population of current and former smokers. |
| Change from baseline in post-bronchodilator FEV1 (mL) in former smokers | Week 52 | Change from baseline in post-bronchodilator FEV1 (mL) in former smokers. |
| Change from baseline in post-bronchodilator FEV1 (mL) in former smokers or current smokers | Week 52 | Change from baseline in post-bronchodilator FEV1 (mL) in former smokers or current smokers. |
| Annualised rate of COPD exacerbations requiring hospitalisations and/or Emergency Room (ER)/Emergency Department (ED) visits in former smokers | Variable duration period up to study completion, approximately 3 years | The rate ratio of COPD exacerbations requiring hospitalisations and/or Emergency Room (ER)/Emergency Department (ED) visits in former smokers. |
| Annualised rate of COPD exacerbations requiring hospitalisations and/or Emergency Room (ER)/Emergency Department (ED) visits in former or current smokers | Variable duration period up to study completion, approximately 3 years | The rate ratio of COPD exacerbations requiring hospitalisations and/or Emergency Room (ER)/Emergency Department (ED) visits in former or current smokers. |
| Change from baseline in pre-BD, pre-dose trough FEV1 (mL) | 52 weeks | Change from baseline in pre-BD, pre-dose trough FEV1 (mL). |
| Change from baseline in post-BD FEV1 (mL) | Over 52 weeks | Change from baseline in post-BD FEV1 (mL). |
| Time to first moderate to severe COPD exacerbation | Over 52 weeks | Time to first moderate to severe COPD exacerbation compared with placebo. |
| Time to first severe COPD exacerbation | Variable duration period up to study completion, approximately 3 years | Time to first severe COPD exacerbation compared with placebo. |
| Change from baseline in CAT total score | Week 52 | Change from baseline in CAT total score compared with placebo. |
| Proportion of participants achieving MCID in CAT score | Week 52 | Proportion of participants achieving MCID in CAT score (percentage of participants with a decrease in CAT total score of ≥ 2 points from baseline). |
| Proportion of participants achieving MCID in SGRQ total score | Week 52 | Proportion of participants achieving MCID in SGRQ score (percentage of participants with a decrease in SGRQ total score of ≥ 4 points from baseline). |
| Proportion of participants achieving MCID in E-RS:COPD total score | Week 52 | Proportion of participants achieving MCID in E-RS:COPD total score (percentage of participants with a decrease in E-RS:COPD total score of ≥ 2 points from baseline). |
| Annualized rate of healthcare resource utilization | Variable duration period up to study completion, approximately 3 years | Annualized rate of healthcare resource utilization. |
| Change from baseline in rescue medication | Over 52 weeks | Change from baseline (difference in mean number of puffs/day) in rescue medication use. |
| Trough serum concentrations of tozorakimab | Over 52 weeks | Pharmacokinetics: concentrations of tozorakimab in trough serum. |
| Presence of anti-drug antibodies | Over 52 weeks | Immunogenicity: presence of tozorakimab anti-drug antibodies in blood serum. |
| Time to death | Variable duration period up to study completion, approximately 3 years | Time to death (all-cause mortality) |
Countries
Argentina, Belgium, Brazil, Bulgaria, Canada, Chile, China, Denmark, France, Germany, Greece, Hungary, India, Ireland, Italy, Japan, Malaysia, Mexico, Netherlands, Peru, Poland, South Korea, Spain, Thailand, Turkey (Türkiye), Ukraine, United Kingdom, United States, Vietnam
Outcome results
None listed