A Study to Investigate the Efficacy and Safety of Tezepelumab in Adult Participants with Moderate to Very Severe Chronic Obstructive Pulmonary Disease (EMBARK)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

6 Jun 2025 → ongoing

Decision date (initial)

2025-05-14

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2024-517458-90-00

ClinicalTrials.gov

NCT06883305

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacogenetic, Pharmacogenomic, Dose response, Safety, Efficacy, Pharmacodynamic

To compare the effect of tezepelumab with placebo on moderate or severe COPD exacerbations in participants with moderate to very severe COPD

Secondary objectives 11

1. 2. To compare the effect of tezepelumab with placebo on post-BD lung function in participants with moderate to very severe COPD.
2. 3. To compare the effect of tezepelumab with placebo on HRQL (SGRQ total score) in participants with moderate to very severe COPD.
3. 4. To compare the effect of tezepelumab with placebo on moderate or severe COPD exacerbations in participants with moderate to very severe COPD and screening EOS ≥ 300 cells/μL.
4. 5. To compare the effect of tezepelumab with placebo on severe COPD exacerbation.
5. 7. To compare the effect of tezepelumab with placebo on HRQL(SGRQ responder) in participants with moderate to very severe COPD.
6. 8. To compare the effect of tezepelumab with placebo on COPD health status (CAT total score, CAT responder) in participants with moderate to very severe COPD.
7. 9. To compare the effect of tezepelumab with placebo on time to first moderate to severe COPD exacerbation.
8. 10. To compare the effect of tezepelumab with placebo on time to first severe COPD exacerbation.
9. 11. To assess the PK and immunogenicity of tezepelumab in participants with moderate to very severe COPD.
10. 1. To compare the effect of tezepelumab with placebo on pre-BD lung function in participants with moderate to very severe COPD.
11. 6. To compare the effect of tezepelumab with placebo on exacerbations requiring ER visit and/or hospitalisation in participants with moderate to very severe COPD.

Conditions and MedDRA coding

Chronic obstructive pulmonary disease (COPD)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 1. Adult participants 40 to 80 years of age at the time of signing the informed consent.
2. 2. Documented physician-diagnosed COPD for at least 12 months before Visit 1.
3. 3. A post-BD FEV1/FVC < 0.70 and a post-BD FEV1 ≥ 20% and ≤70% of the predicted normal value during screening.
4. 4. Documented regular dose of triple inhaled maintenance therapy (ICS+LABA+LAMA), or dualtherapy (LABA+LAMA, ICS+LABA, ICS+LAMA) if triple therapy is considered not appropriate, for atleast 3 consecutive months before Visit 1.
5. 5. Documented history ≥2 moderate or ≥1 severe COPD exacerbations within 12 months before Visit 1. At least 1 of the 2 moderate exacerbations must have been treated with SCS. At least one of the previous exacerbations should be confirmed to have occurred while the participant was on triple or dual inhaled maintenance therapy.
6. 6. EOS ≥ 150 cells/μL during the screening period.
7. 7. CAT total score ≥ 15 at Visit 1.
8. 8. Current or former smokers (with smoking cessation ≥ 6 monthsbefore Visit 1) have a history of at least 10 pack-years of tobacco smoking (1 pack year = 20 cigarettes smoked per day for 1 year).

Exclusion criteria 12

1. 1. Clinically important lung disease other than COPD (eg, active lung infection, clinically significant bronchiectasis, pulmonary fibrosis,cystic fibrosis, hypoventilation syndrome associated with obesity,lung cancer, alpha 1 anti-trypsin deficiency and primary ciliary dyskinesia), or another diagnosed pulmonary or systemic disease that is associated with elevated peripheral EOS (eg, allergic bronchopulmonary aspergillosis/mycosis, eosinophilicgranulomatosis with polyangiitis, hypereosinophilic syndrome).
2. 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 nodulessuspicious for lung cancer, as per applicable guidance, (eg, ACRLung-RADS v2022, (Christensen et al 2024)) without appropriatefollow up before Visit 2.
3. 3. Radiological findings suggestive of acute respiratory infection, if confirmed clinically.
4. 4. Current physician diagnosed asthma according to the Global Initiative for Asthma (GINA 2024 and onwards versions) guidelines or other accepted guidelines, past physician diagnosed asthma including paediatric asthma, or asthma-COPD overlap syndrome.
5. 5. Any unstable disorder, including, but not limited to, cardiovascular,gastrointestinal, hepatic, renal, neurological, musculoskeletal,infectious, endocrine, metabolic, haematological, immune,psychiatric, or major physical/or cognitive impairment that is not stable in the opinion of the investigator or the sponsor and/orcould: − Affect the safety of the participant throughout the study − Influence the findings of the study or their interpretation − Impede the participant’s ability to complete the entire durationof the study and/or comply with the study visit schedule and procedures
6. 6. Unstable cardiovascular disorder (including but not limited toischemic heart disease, arrhythmia, cardiomyopathy, severe right and/or left heart failure (NYHA class IV)), renal failure,uncontrolled hypertension, as defined by the Investigator, or anyother relevant cardiovascular disorder or ECG abnormality that in the Investigator’s judgment may put the participant at risk or negatively affect the outcome of the study.
7. 7. Tuberculosis requiring treatment in the last 12 months before Visit 2. Local guidelines for diagnosis and treatment should be followed.
8. 8. Malignancy, current or past (within 5 years before Visit 1), except for basal cell carcinoma, localised squamous cell carcinoma of thes kin, or in situ carcinoma of the cervix provided when a curative therapy was completed at least 12 months before Visit 1.
9. 9. Treatment with systemic immunosuppressive/immunomodulatingmedications including maintenance use of SCS within the last 12 weeks or 5 half-lives before Visit 1 or during the screening for other reasons than COPD exacerbation. Expected need for chronicuse during the study for any reason.
10. 10. LTOT with signs and/or symptoms of cor pulmonale and/or rightventricular failure, or LTOT > 4.0 litres/minute (L/min) at rest oran oxyhaemoglobin saturation < 89% despite LTOT.
11. 11. Use, or need for chronic use, of any non-invasive positive pressure ventilation device. Stable use of non-invasive ventilation for the treatment of Obstructive Sleep Apnoea is permitted.
12. 12. Maintenance treatment with macrolides or other antibiotics forCOPD if the duration of the treatment is < 6 consecutive months before Visit 1.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Annualised rate of moderate or severe COPD exacerbations up to 76 weeks

Secondary endpoints 12

1. 1. Change from baseline in pre-BD FEV1 at Week 52
2. 3. Change from baseline in the SGRQ total score over 52 weeks
3. 4. Annualised rate of moderate or severe COPD exacerbations up to 76 weeks among participants with screening EOS ≥ 300 cells/μL.
4. 5. Annualised rate of severe COPD exacerbations requiring ER visits and/or hospitalisations up to 76 weeks.
5. 6. Participants achieving a clinically meaningful improvement from baseline in SGRQ total score (4-point score decrease) over 52 weeks.
6. 7. Change from baseline in the CAT total score over 52 weeks
7. 8. Participants achieving a clinically meaningful improvement frombaseline in CAT total score (2-point score decrease) over 52 weeks.
8. 9. Time to first moderate to severe COPD exacerbation up to 76 weeks
9. 10. Time to first severe COPD exacerbation up to 76 weeks
10. 11. PK: Serum trough concentrations
11. 12. Immunogenicity: Incidence of anti-drug antibodies and neutralising antibodies
12. 2. Change from baseline in post-BD FEV1 at Week 52.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AZ Clinical Study Info Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AZ Clinical Study Info Center

Locations

7 EU/EEA countries · 55 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 2 · Art. 52 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 60 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications