Long-term Efficacy and Safety of Tozorakimab in Participants with Chronic Obstructive Pulmonary Disease 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

20 Apr 2023 → 27 May 2026

Decision date (initial)

2023-03-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2022-501063-41-00

ClinicalTrials.gov

NCT05742802

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

To evaluate the long-term effect of tozorakimab as an add on to SoC compared with SoC plus placebo on the rate of severe COPD exacerbations in former smokers.

Secondary objectives 7

1. To evaluate the long-term effect of tozorakimab as an add on to SoC compared with SoC plus placebo on the rate of severe COPD exacerbations in former or current smokers.
2. To evaluate the long-term effect of tozorakimab as an add on to SoC compared with SoC plus placebo on the time to first severe COPD exacerbation.
3. To evaluate the long-term effect of tozorakimab as an add on to SoC compared with SoC plus placebo on the time to first moderate to severe COPD exacerbation.
4. To evaluate the long-term effect of tozorakimab as an add on to SoC compared with SoC plus placebo on the rate of moderate to severe COPD exacerbations.
5. To evaluate the effect of tozorakimab as an add on to SoC compared with SoC plus placebo on time to all-cause death.
6. To evaluate the pharmacokinetics and immunogenicity of tozorakimab.
7. To evaluate the long-term effect of tozorakimab as an add on to SoC compared to with SoC plus placebo on COPD related health care utilisation.

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 5

1. Participants who have completed the treatment period and have not been prematurely discontinued from IP in the predecessor studies.
2. Participants who received their last dose of IP in the predecessor studies within the previous 12 weeks and were not withdrawn from the predecessor study.
3. FOCBP (female(s) of childbearing potential) must have a negative urine pregnancy test at Visit 1.
4. Participants who are willing to continue using contraceptive methods as agreed to for the predecessor OBERON or TITANIA studies.
5. Capable of giving signed informed consent.

Exclusion criteria 7

1. Any clinically significant disorder or abnormal findings (clinical, laboratory, instrumental, etc) or major physical and/or cognitive impairment, which, in the opinion of the Investigator, may put the participant at risk because of his/her participation in the study or impact the interpretation of the study results, or otherwise makes the participation of the participant inappropriate.
2. Participant meeting criteria for IP discontinuation as judged by the Investigator or the Sponsor.
3. Concurrent enrolment in other interventional clinical studies or treatment with another IP, with the exception of the OBERON and TITANIA predecessor studies.
4. Known history of: (a) Severe allergic reaction to any monoclonal and polyclonal antibody. (b) Allergy or reaction to any component of the IP formulation.
5. Chronic use (or expected need for chronic use during the study) of immunosuppressive medications (including, but not limited to, systemic corticosteroids), marketed or investigational biologic, or another prohibited medication.
6. Involvement in the planning and/or conduct of the study (applies to both staff employed by the Sponsor and/or staff at the study site).
7. Participants who are not able to comply with the study requirements, procedures, and restrictions.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Annualized rate of severe COPD exacerbation for Tozorakimab versus placebo in former smokers.

Secondary endpoints 11

1. Annualised rate of severe COPD exacerbations in former or current smokers.
2. Time to first severe COPD exacerbations in former smokers.
3. Time to first severe COPD exacerbations in former or current smokers.
4. Time to First Moderate to Severe COPD Exacerbation.
5. Annualised Rate of Moderate-to-Severe COPD Exacerbations.
6. Time to Death (All-cause mortality).
7. Pharmacokinetics
8. Immunogenicity
9. To assess the long-term safety and tolerability of tozorakimab
10. Annualised rate of COPD exacerbations requiring hospitalisation and/or ER/ED visits in former smokers.
11. Annualised rate of COPD exacerbations requiring hospitalisation and/or ER/ED visits in former or current 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

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

Astrazeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

Astrazeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

17 EU/EEA countries · 137 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 1 · 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 123 files

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

Application history

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