Long-term Efficacy and Safety of Tozorakimab in Participants With Chronic Obstructive Pulmonary Disease With a History of Exacerbations.

Study Overview
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Brief Summary
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Subjects who completed either OBERON or TITANIA will be offered the opportunity to consent for this Multicentre, Double-blind, Randomised, Placebo controlled, Parallel Group, Phase 3, extension study to evaluate the safety and efficacy of Tozorakimab in adult participants with symptomatic COPD.

Detailed Description
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Participants who have completed the study treatment period and have not been prematurely discontinued from IP in one of the predecessor studies, OBERON or TITANIA, will be offered the opportunity to consent for this Multicentre, Double-blind, Randomised, Placebo-controlled, Parallel Group, Phase 3 extension study to evaluate the efficacy and safety of Tozorakimab versus placebo in adult (40 years and older) participants with symptomatic COPD and with a history of exacerbations

Official Title
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A Phase III, Multicentre, Randomised, Double-blind, Chronic-dosing, Parallel-group, Placebo-controlled Extension Study to Evaluate the Long-term Efficacy and Safety of Tozorakimab (MEDI3506) in Participants With Chronic Obstructive Pulmonary Disease (COPD) With a History of Exacerbations.

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Combination Product: Tozorakimab
* Combination Product: Tozorakimab
* Combination Product: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who have completed the treatment period and have not been prematurely discontinued from IP in the predecessor studies. Participants who received their last dose of IP in the predecessor studies within the previous 12 weeks and were not withdrawn from the predecessor study. FOCBP (female(s) of childbearing potential) must have a negative urine pregnancy test at Visit 1. Participants who are willing to continue using contraceptive methods as agreed to for the predecessor OBERON or TITANIA studies. Capable of giving signed informed consent. Exclusion Criteria: 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 make the participation of the participant inappropriate. Participant meeting criteria for IP discontinuation as judged by the Investigator or the Sponsor. Concurrent enrolment in other interventional clinical studies or treatment with another IP, with the exception of the OBERON and TITANIA predecessor studies. Known history of: Severe allergic reaction to any monoclonal and polyclonal antibody. Allergy or reaction to any component of the IP formulation. 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. 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). Participants who are not able to comply with the study requirements, procedures, and restrictions.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tozorakimab Dose 1<br>Injection subcutaneously Tozorakimab or placebo via pre-filled syringe. | Combination Product: Tozorakimab<br>* Participants previously randomised to Tozorakimab in one of the predecessor studies will be assigned to the same Tozorakimab dose and regimen in the PROSPERO study.<br>|
| Experimental: Tozorakimab Dose 2<br>Injection subcutaneously Tozorakimab via pre-filled syringe. | Combination Product: Tozorakimab<br>* Participants previously randomised to Tozorakimab in one of the predecessor studies will be assigned to the same Tozorakimab dose and regimen in the PROSPERO study.<br>|
| Placebo Comparator: Placebo<br>Injection subcutaneously with equivalent volume to Tozorakimab via pre-filled syringe. | Combination Product: Placebo<br>* Participants previously randomised to placebo in one of the predecessor studies will be reassigned to one of the active doses of Tozorakimab or placebo in a 1:1:2 ratio.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first severe COPD exacerbation in former smokers. | The primary efficacy endpoint is the time to first severe COPD exacerbation over the treatment period incorporating both the predecessor studies and PROSPERO. The primary endpoint will be assessed first in the Primary Population of former smokers, followed by the Overall Population of current and former smokers. | 104 weeks total (52 weeks in this study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first severe COPD exacerbation. | To be analysed as a key secondary endpoint in the Overall Population of current and former smokers. | 104 weeks total (52 weeks in this study) | 
| Annualised rate of severe COPD exacerbations. | The annualised rate of severe COPD exacerbations over the treatment period. Analyses will be conducted in the former smoker population, followed by the Overall Population of current and former smokers. | 104 weeks total (52 weeks in this study) | 
| Time to first moderate-to-severe COPD exacerbation. | To explore the extent to which treatment with each dose of Tozorakimab delays the time to first exacerbation compared with placebo. | 104 weeks total (52 weeks in this study) | 
| Annualised rate of moderate to severe COPD exacerbations. | To evaluate the effect of Tozorakimab as an add on to SoC compared with SoC plus placebo on the rate of moderate to severe COPD exacerbations. | 104 weeks total (52 weeks in this study) | 
| Time to all-cause death. | To evaluate the effect of Tozorakimab as an add on to SoC compared with SoC plus placebo on time to all-cause death. | 104 weeks total (52 weeks in this study) | 
| Trough serum concentrations of tozorakimab over the treatment period. | Pharmacokinetics: concentrations of Tozorakimab in trough serum. | 104 weeks total (52 weeks in this study) | 
| Incidence of anti-drug antibodies. | Immunogenicity: presence of Tozorakimab anti-drug antibodies in blood serum. | 104 weeks total (52 weeks in this study) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Obstructive Pulmonary Disease, COPD, Tozorakimab, MEDI3506, exacerbations, LABA/LAMA, ICS