Study to assess efficacy, safety, and tolerability of Tozorakimab in patients with symptomatic chronic obstructive pulmonary disease (COPD) with a history of exacerbations.

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

2 Mar 2022 → 22 Mar 2026

Decision date (initial)

2024-05-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Astra Zeneca AB

External identifiers

EU CT number

2023-503572-24-00

EudraCT number

2021-003771-34

ClinicalTrials.gov

NCT05158387

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

To evaluate the effect of 2 dose regimens of tozorakimab as addon to standard of care compared with standard of care plus placebo on the rate of moderate to severe exacerbations in former smokers.

Secondary objectives 3

1. 1. To evaluate the effect of 2 dose regimens of tozorakimab as addon to standard of care compared with standard of care plus placebo on: a) the rate of moderate to severe COPD exacerbations in former and current smokers b) change in pre-bronchodilator lung function c) change in post-bronchodilator lung function d) respiratory symptoms e) respiratory health status/health related quality of life f) time to first moderate to severe COPD exacerbations g) severe COPD exacerbations h) COPD health status/health-related quality of life i) COPD-related healthcare resource utilization j) daily rescue medication use
2. 2. To evaluate the pharmacokinetics and immunogenicity of 2 dose regimens of tozorakimab
3. 3. To assess the safety and tolerability of two dose regimen of tozorakimab as add on to standard of care compared with standard of care plus placebo

Conditions and MedDRA coding

Chronic Obstructive Pulmonary Disease (COPD)

Regulatory references

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 7

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

Exclusion criteria 18

1. 1. Clinically important pulmonary disease other than COPD.
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 nodules suspicious for lung cancer, as per applicable guidances, without appropriate follow up prior to randomization. Radiological findings suggestive of acute infection.
3. 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. 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. 5. COPD exacerbation, within 2 weeks prior to randomization, that was treated with systemic corticosteroids and/or antibiotics, and/or led to hospitalization.
6. 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. 7. Suspicion of, or confirmed, ongoing SARS-CoV-2 infection.
8. 8. Significant COVID-19 illness within the 6 months prior to enrolment.
9. 9. Unstable cardiovascular disorder.
10. 10. Diagnosis of cor pulmonale, pulmonary arterial hypertension and/or right ventricular failure.
11. 11. History of known immunodeficiency disorder, including a positive test for HIV-1 or HIV 2.
12. 12. History of positive test or treatment for hepatitis B or hepatitis C (except for cured hepatitis C)
13. 13. Evidence of active liver disease, including jaundice during screening.
14. 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. 15. Participants who have evidence of active TB.
16. 16. Participants that have previously received tozorakimab.
17. 17. 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.
18. 18. Active vaping of any products or using smoked marijuana within the 6 months prior to randomization and during the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Annualized rate of moderate to severe COPD exacerbations in participants who are former smokers.

Investigational products

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

Test 1

Placebo 1

Auxiliary 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

Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

Clinical Study Information Center

Locations

6 EU/EEA countries · 62 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 44 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