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

Phase 2

Completed

Conditions: Chronic Obstructive Pulmonary Disease (COPD)

Interventions: Other: Placebo
Drug: Mitiperstat (AZD4831)

Registration Number: NCT05492877

Lead Sponsor: AstraZeneca

Brief Summary: 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: 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 406 participants will be randomised to two treatment groups; Mitiperstat (AZD4831) vs placebo in a 1:1 ratio.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 381

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Approximately 203 participants will be randomised to receive placebo.
Mitiperstat (AZD4831)	Mitiperstat (AZD4831)	Approximately 203 participants will be randomised to receive mitiperstat (AZD4831).

Primary Outcome Measures

Name	Time	Method
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.	From baseline to up to 24 weeks	COPDCompEx is a composite endpoint of exacerbations and events defined from participant e-Diaries and peak expiratory flow (PEF). COPDCompEx defined exacerbations included episodes leading to one or more of the following: hospitalization, emergency room visit, treatment with systemic corticosteroids (injected and/or oral), or treatment with antibiotics. Diary COPDCompEx events are defined by threshold and slope criteria being met for \>= 2 consecutive days using the following diary and home spirometry variables: overall symptom rating, night-time awakenings due to symptoms, reliever medication use, PEF. COPDCompEx also includes patient withdrawals for treatment failure.

Secondary Outcome Measures

Name	Time	Method
To Assess the PK of Mitiperstat (AZD4831) in Patients With Moderate to Severe COPD	At week 12	Measurement of Time to Reach Maximum Plasma Concentration (Tmax) at pre-randomisation (baseline visit) and week 12.
To Assess the Pharmacokinetics (PK) of Mitiperstat (AZD4831) in Patients With Moderate to Severe COPD.	At week 12	Measurement of Maximum Plasma Concentration (Cmax) at pre-randomisation (baseline visit) and week 12.
To Evaluate the Effect of Mitiperstat (AZD4831) as Compared to Placebo on the Time to First Moderate or Severe Exacerbation.	From baseline to up to week 24	A COPD exacerbation was considered moderate if it required treatment with systemic corticosteroids and/or antibiotics for at least 3 days or resulted in emergency room visit\< 24 hours requiring intensive treatment; and did not result in hospitalization or death. A COPD exacerbation was considered severe if it resulted in hospitalization (defined as an inpatient admission ≥ 24 hours in the hospital, an observation area, the emergency department, or other equivalent healthcare facility depending on the country and healthcare system) or death due to COPD.
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.	From baseline to week 12	The mean change from baseline in Post-BD FEV1 at Week 12 was estimated using a repeated measures mixed effects analysis of covariance. Only subjects with non-missing covariates are included in the analysis. FEV1 was measured by spirometry at clinic.
To Assess the Effect of Mitiperstat (AZD4831) Compared to Placebo on Respiratory Symptoms in Patients With Moderate to Severe COPD.	From baseline to week 12 and week 24	Change from baseline to Week 12 and week 24 in mean Breathlessness, Cough and Sputum Scale (BCSS) score is reported. The BCSS was a 3-item daily diary that assesses the severity of the 3 symptoms: breathlessness, sputum, and cough, each on a 5-point Likert scale ranging from 0 (no symptoms) to 4 (severe symptoms). Item scores were summed to yield a total score ranging from 0 to 12; wherein higher total score indicated more severe symptoms. The BCSS was captured each evening via eDiary.
To Assess the Effect of Mitiperstat (AZD4831) Compared to Placebo in Disease Impact in Patients With Moderate to Severe COPD.	From baseline to week 12 and week 24	Change from baseline to Week 12 and week 24 in cough Visual Analogue Scale (VAS) score is reported. Participants were asked to complete a cough severity VAS (100-point linear scale marked with a horizontal line by the participant, with 0 representing ''no cough'' and 100 representing "worst cough") that measured subjective assessment by the participant of the prior 24 hrs for severity of cough symptoms. It was completed each evening in the eDiary.
Change From Baseline to Week 12 in Total COPD Assessment Test (CAT)	From baseline to Week 12	COPD Assessment Test (CAT) is designed to measure how COPD impacts on a patient's daily life and how this might change over time. It consists of 8 questions that ask the patient to rate items relating to symptoms and impact on quality of life (such as normal activity and sleep). Each question is performed on a 5-point Likert scale from 0 (no symptoms/no impact) to 5 (severe symptoms/impact). The CAT will be completed by participants at on-site visits using the e-Diary.