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.

Study Timeline

• Study First Submitted: 2022-07-22
• Study First Submitted QC: 2022-08-05
• Study First Posted: 2022-08-09
• Study Start: 2022-11-14
• Primary Completion: 2024-08-12
• Study Completion: 2024-08-12
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-21
• Last Update Posted: 2024-11-22

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	All patients randomised to either active or placebo arm.

Secondary Outcome Measures

Name	Time	Method
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	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).
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	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).
To assess the pharmacokinetics (PK) of mitiperstat (AZD4831) in patients with moderate to severe COPD.	Baseline and week 12 (or at early discontinuation visit due to rash)	Measurement of Maximum Plasma Concentration (Cmax) at pre-randomisation (baseline visit) 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.	From baseline to up to week 24	All patients randomised to either active or placebo arms.
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	All patients randomised to either active or placebo arms. Change in post-BD FEV1.
To assess the PK of mitiperstat (AZD4831) in patients with moderate to severe COPD	Baseline and week 12 (or at early discontinuation visit due to rash)	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).

Trial Locations

Locations (1)

Research Site; 🇬🇧 York, United Kingdom