TOZORAKIMAB for Chronic obstructive pulmonary disease

Inclusion criteria

• {"criterion_text":"- 1. Participant must be ≥ 40 years of age and capable of giving signed informed consent\n- 2. Documented diagnosis of COPD for at least one year prior to enrolment\n- 3. Post BD FEV1/FVC < 0.70 and post-BD FEV1 >20% of predicted normal value\n- 4. Documented history of ≥ 2 moderate or ≥ 1 severe COPD exacerbations within 12 months prior to enrolment\n- 5. Documented optimised inhaled dual or triple therapy for at least 3 months prior to enrolment\n- 6. Smoking history of ≥ 10 pack-years\n- 7. CAT total score ≥ 10, with each of the phlegm (sputum) and cough items with a score ≥ 2"}

Exclusion criteria

• {"criterion_text":"- Clinically important pulmonary disease other than COPD.\n- History of partial or total lung resection.\n- Participants that have previously received tozorakimab.\n- History of positive test or treatment for hepatitis B or hepatitis C (except for cured hepatitis C)\n- Unstable cardiovascular disorder.\n- 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.\n- History of known immunodeficiency disorder, including a positive test for HIV-1 or HIV 2.\n- Diagnosis of cor pulmonale, pulmonary arterial hypertension and/or right ventricular failure.\n- 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.\n- 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.\n- 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.\n- Scheduled major surgical procedure during the course of the study.\n- 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.\n- 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.\n- COPD exacerbation, within 2 weeks prior to randomization, that was treated with systemic corticosteroids and/or antibiotics, and/or led to hospitalization.\n- Evidence of active liver disease, including jaundice during screening.\n- 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.\n- Suspicion of, or confirmed, ongoing SARS-CoV-2 infection.\n- Significant COVID-19 illness within the 6 months prior to enrolment.\n- Participants who have evidence of active TB."}

Primary endpoints

• {"endpoint_text":"- Annualized rate of moderate to severe COPD exacerbations in participants who are former smokers.","definition_or_measurement_approach":"Annualized rate of moderate to severe COPD exacerbations measured as the annualised exacerbation rate in former smokers."}

Secondary endpoints

• {"endpoint_text":"- Annualized rate of moderate to severe COPD exacerbations in former or current smokers","definition_or_measurement_approach":""}
• {"endpoint_text":"- Change from baseline in SGRQ total score in former smokers","definition_or_measurement_approach":""}
• {"endpoint_text":"- Change from baseline in SGRQ total score in former or current smokers","definition_or_measurement_approach":""}
• {"endpoint_text":"- Annualized rate of severe COPD exacerbations in former smokers","definition_or_measurement_approach":""}
• {"endpoint_text":"- Annualized rate of severe COPD exacerbations in former or current smokers","definition_or_measurement_approach":""}
• {"endpoint_text":"- Change from baseline in E-RS:COPD total score in former smokers","definition_or_measurement_approach":""}
• {"endpoint_text":"- Change from baseline in E-RS:COPD total score in former or current smokers","definition_or_measurement_approach":""}
• {"endpoint_text":"- Change from baseline in pre-bronchodilator, pre dose trough FEV1 (mL) in former smokers","definition_or_measurement_approach":""}
• {"endpoint_text":"- Change from baseline in pre-bronchodilator, pre dose trough FEV1 (mL) in former or current smokers","definition_or_measurement_approach":""}
• {"endpoint_text":"- Time to first moderate to severe COPD exacerbation","definition_or_measurement_approach":""}
• {"endpoint_text":"- Time to first severe COPD exacerbation","definition_or_measurement_approach":""}
• {"endpoint_text":"- Change from baseline in CAT total score","definition_or_measurement_approach":""}
• {"endpoint_text":"- Proportion of participants achieving MCID in CAT score","definition_or_measurement_approach":""}
• {"endpoint_text":"- Proportion of participants achieving MCID in SGRQ total score","definition_or_measurement_approach":""}
• {"endpoint_text":"- Proportion of participants achieving MCID in E-RS:COPD total score","definition_or_measurement_approach":""}
• {"endpoint_text":"- Annualized rate of healthcare resource utilization","definition_or_measurement_approach":""}
• {"endpoint_text":"- Change from baseline in rescue medication","definition_or_measurement_approach":""}
• {"endpoint_text":"- Trough serum concentrations of tozorakimab","definition_or_measurement_approach":""}
• {"endpoint_text":"- Presence of anti-drug antibodies","definition_or_measurement_approach":""}
• {"endpoint_text":"- Time to death","definition_or_measurement_approach":""}
• {"endpoint_text":"- Safety and tolerability","definition_or_measurement_approach":""}
• {"endpoint_text":"- Change from baseline in post-bronchodilator FEV1 (mL) in former smokers","definition_or_measurement_approach":""}
• {"endpoint_text":"- Change from baseline in post-bronchodilator FEV1 (mL) in former or current smokers","definition_or_measurement_approach":""}
• {"endpoint_text":"- Annualized rate of COPD exacerbations requiring hospitalisations and/or Emergency Room /Emergency Department visits in former smokers","definition_or_measurement_approach":""}
• {"endpoint_text":"- Annualised rate of COPD exacerbations requiring hospitalisations and/or Emergency Room /Emergency Department visits in former or current smokers","definition_or_measurement_approach":""}

Methods

• Posters (site posters) — recruitment materials present (K2_Recruitment material Poster) for multiple countries.
• Flyers / print advertisements (K2 recruitment flyers and print ads).
• Web/online recruitment: landing page and web banner ads (documented as 'landingpage', 'web_print_banner_ad').
• Patient letters / database mailings ('patientletter_database').
• Study Summary Tool and Patient Study Guide (K2 recruitment materials) provided to potential participants.
• Country-specific recruitment arrangements documents (K1) and James Lind Care arrangements in some countries.

Primary sponsor

Full Name

Astrazeneca AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden