An Efficacy and Safety Study of Mitiperstat (AZD4831) (MPO Inhibitor) vs Placebo in the Treatment of Moderate to Severe COPD.

Study Overview
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Brief Summary
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This is a research study to evaluate the efficacy and safety of the investigational drug Mitiperstat (AZD4831) in adult patients with chronic obstructive pulmonary disease.

Detailed Description
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Study D6582C00001 is a phase IIa randomised, double blind, placebo controlled, parallel arm study to evaluate the efficacy and safety of Mitiperstat (AZD4831) in adult participants with moderate to severe chronic obstructive pulmonary disease. Approximately 100 sites globally will participate in this study. Approximately 288 participants will be randomised to two treatment groups; Mitiperstat (AZD4831) vs placebo in a 1:1 ratio.

Official Title
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A Phase IIa Randomised, Double Blind, Placebo Controlled, Parallel Arm, Multi-Centre Study to Evaluate the Efficacy and Safety of Mitiperstat (AZD4831), for 12-24 Weeks, in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Drug: Mitiperstat (AZD4831)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of informed consent. Participants must be deemed as high risk of exacerbations as defined by: >= 1 moderate or severe exacerbation in the previous 24 months; or frequent productive cough; or post-bronchodilator (BD) forced expiratory volume in the first second (FEV1) < 50% predicted. Participants must be 40-80 years of age inclusive, at the time of signing informed consent form (ICF). Participants who have a confirmed primary diagnosis of moderate to severe COPD. Participants who are current or ex-smokers with a tobacco history of ≥ 10 pack-years. Participants who have a documented stable regimen of triple therapy or dual therapy for ≥ 3 months prior to enrolment. Body mass index within the range 18 to 40 kg/m2 (inclusive). Exclusion Criteria: As judged by the investigator, any evidence of any active medical or psychiatric condition or other reason (at SV1 [screening] and SV3 [pre-dose]) which in the investigator's opinion makes it undesirable for the participant to participate in the study. Current diagnosis of asthma or past diagnosis of asthma which persisted beyond the age of 25 years. Clinically important pulmonary disease other than COPD. Any other clinically relevant abnormal findings on physical examination, laboratory testing including haematology, coagulation, serum chemistry, or urinalysis; or chest CT scan at screening or randomisation, which in the opinion of the investigator or medical monitor may compromise the safety of the participant in the study or interfere with evaluation of the study intervention or reduce the participant's ability to participate in the study. History of a clinically significant infection (viral, bacterial, or fungal; defined as requiring systemic antibiotics, antiviral, or antifungal medication for > 7 days) within 4 weeks prior to SV3 (Day 1) (including unexplained diarrhoea) or clinical suspicion of infection at time of dosing.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 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
Interventional Model Description: Participants will be randomised to receive either Mitiperstat (AZD4831) or placebo.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Approximately 144 participants will be randomised to receive placebo. | Other: Placebo<br>* Oral dosage, once daily.<br>|
| Experimental: Mitiperstat (AZD4831)<br>Approximately 144 participants will be randomised to receive mitiperstat (AZD4831). | Drug: Mitiperstat (AZD4831)<br>* Oral dosage, once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effect of mitiperstat (AZD4831) as compared to placebo on the time to first COPD Composite Exacerbation (CompEx) event in patients with moderate to severe COPD. | All patients randomised to either active or placebo arm. | From baseline to up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the pharmacokinetics (PK) of mitiperstat (AZD4831) in patients with moderate to severe COPD. | Measurement of Maximum Plasma Concentration (Cmax) at pre-randomisation (baseline visit) and week 12 (or at early discontinuation visit due to rash). | Baseline and week 12 (or at early discontinuation visit due to rash) | 
| To assess the PK of mitiperstat (AZD4831) in patients with moderate to severe COPD | Measurement of Time to Reach Maximum Plasma Concentration (Tmax) at pre-randomisation (baseline visit) and week 12 (or at early discontinuation visit due to rash). | Baseline and week 12 (or at early discontinuation visit due to rash) | 
| To evaluate the effect of mitiperstat (AZD4831) as compared to placebo on the time to first moderate or severe exacerbation. | All patients randomised to either active or placebo arms. | From baseline to up to week 24 | 
| To assess the effects of mitiperstat (AZD4831) as compared to placebo on post-bronchodilator (BD) forced expiratory volume in the first second (FEV1) in patients with moderate to severe COPD. | All patients randomised to either active or placebo arms. Change in post-BD FEV1. | From baseline to week 12 | 
| To assess the effect of mitiperstat (AZD4831) compared to placebo on respiratory symptoms in patients with moderate to severe COPD. | All patients randomised to either active or placebo arms. Change from baseline in EXAcerbations of Chronic Pulmonary Disease Tool (EXACT) which is a 14-item ePRO instrument developed to assess the frequency, severity and duration of COPD exacerbations. | From baseline to week 12 and week 24 | 
| To assess the effect of mitiperstat (AZD4831) compared to placebo on respiratory symptoms in patients with moderate to severe COPD. | All patients randomised to either active or placebo arms. Change from baseline in Breathlessness, Cough and Sputum Score (BCSS) with the 5-point Likert scale ranging from 0 (no symptoms) to 4 (severe symptoms). | From baseline to week 12 and week 24 | 
| To assess the effect of mitiperstat (AZD4831) compared to placebo on respiratory symptoms in patients with moderate to severe COPD. | All patients randomised to either active or placebo arms. Change from baseline in cough Visual Analogue Scale (cough VAS) with the 100-point linear scale ranging from 0 (no cough) to 100 (worst cough). | From baseline to week 12 and week 24 | 
| To assess the effect of mitiperstat (AZD4831) compared to placebo in disease impact in patients with moderate to severe COPD. | All patients randomised to either active or placebo arms. Change from baseline in total COPD Assessment Test (CAT) with the 5-point Likert scale ranging from 0 (no symptoms/no impact) to 5 (severe symptoms/impact). | From baseline to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mitiperstat, AZD4831, Myeloperoxidase, MPO, Myeloperoxidase inhibitor, COPD, Chronic Obstructive Pulmonary Disease, Lung function