Clinical trial NCT06897748: A Study to Investigate Efficacy and Safety of Tozorakimab Injections Compared With Placebo in Adult Participants With Symptomatic Chronic Obstructive Pulmonary Disease (COPD) With a History of COPD Exacerbations and Elevated Eosinophils
Official title: A Phase II, Multicentre, Randomised, Double-blind, Parallel-group, Placebo-controlled Study to Evaluate the Efficacy and Safety of Tozorakimab in Participants With Symptomatic Chronic Obstructive Pulmonary Disease (COPD) With a History of COPD Exacerbations and Elevated Eosinophils (COMETA)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Chronic Obstructive Pulmonary Disease (COPD)
Keywords: Chronic Obstructive Pulmonary Disease
COPD
tozorakimab
MEDI3506
ICS
LABA/LAMA
Biologic
Biologic Treatment
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2025-03-27
Enrollment: 98
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate lung function parameters, composite endpoint for exacerbations in chronic obstructive pulmonary disease (COPDCompEx), symptoms and to provide safety information after tozorakimab or placebo administrations in participants with symptomatic chronic obstructive pulmonary disease (COPD) with history of exacerbations and high blood eosinophil counts.

Study details include the following:

* The maximum duration of the screening/run-in period is 5 weeks. An additional unscheduled visit may be performed prior to randomization to repeat safety assessments as deemed necessary by the investigator.
* Eligible patients will enter 12-week treatment (intervention) period with site visits and investigational product (IP) administration every 2 weeks.
* Participants who complete a treatment period, and have not been prematurely discontinued from IP, will enter a 10-week post-intervention follow-up period.
* The study duration will be 27 weeks at maximum for each participant.


Eligibility criteria: 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% and \< 80% 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.
8. All participants must have eosinophil blood count ≥ 150 cells/µL.

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. Significant COVID-19 illness within the 6 months prior to enrolment.
8. Unstable cardiovascular disorder.
9. Diagnosis of clinically significant cor pulmonale, pulmonary arterial hypertension and/or right ventricular failure.
10. 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.
11. History of known immunodeficiency disorder, including a positive test for HIV-1 or HIV 2.
12. History of positive test or treatment for hepatitis B or hepatitis C (except for cured hepatitis C).
13. Evidence of active liver disease, including jaundice during screening.
14. 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.
15. Participants who, in the opinion of the Investigator or qualified designee, have evidence of active TB.
16. History of partial or total lung resection.
17. Scheduled major surgical procedure during the course of the study.
18. Participants that have previously received tozorakimab.
19. Change in smoking status in 12 weeks prior to enrolment or intention to change smoking status between enrolment and end of follow-up.
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.

Primary outcomes:
measure: Change From Baseline to Week 12 in Pre-bronchodilator Forced Expiratory Volume in 1 Second (Pre-BD FEV1) as Measured in Clinic
timeFrame: Baseline through Week 12
Secondary outcomes:
measure: Annualized rate of composite endpoint for exacerbations in COPD (COPDCompEx) events
timeFrame: From baseline to Week 12 and Week 22
measure: Change from baseline in pre-BD and post-BD FEV1
timeFrame: From baseline through Week 22
measure: Change from baseline in pre-BD and post-BD forced vital capacity (FVC)
timeFrame: From baseline through Week 22
measure: FEV1 % reversibility dynamics
timeFrame: From baseline to Week 22
measure: Change from baseline in peak expiratory flow (PEF) measured in clinic and at home
timeFrame: From baseline through Week 22
measure: Change from baseline in home FEV1
timeFrame: From baseline through Week 22
measure: Time to first COPDCompEx event
timeFrame: From baseline to Week 12 and Week 22
measure: Change from baseline in mean Breathless, cough and sputum scale (BCSS) score
timeFrame: From baseline to Week 12 and Week 22
measure: Change from baseline in COPD assessment test (CAT) total score
timeFrame: From baseline to Week 12 and Week 22
Other outcomes:
measure: Number of patients with adverse events (AEs)
timeFrame: Through study completion, up to 27 weeks
Locations:
city: Izhevsk
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Omsk
country: Russian Federation
facility: Research Site
city: Penza
country: Russian Federation
facility: Research Site
city: Perm
country: Russian Federation
facility: Research Site
city: Saratov
country: Russian Federation
facility: Research Site
city: Saratov
country: Russian Federation
facility: Research Site
city: St-Petersburg
country: Russian Federation
facility: Research Site
city: Ulyanovsk
country: Russian Federation
facility: Research Site
Study officials:
References: