Trial Outcomes & Findings for An Efficacy and Safety Study of Mitiperstat (AZD4831) (MPO Inhibitor) vs Placebo in the Treatment of Moderate to Severe COPD. (NCT NCT05492877)

Last Updated: 2025-08-29

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

381 participants

Primary outcome timeframe

From baseline to up to 24 weeks

Results posted on

2025-08-29

Participant Flow

The study was conducted at 101 centers in 14 countries (Argentina, Bulgaria, Canada, Denmark, Germany, Italy, Mexico, Netherlands, Poland, South Africa, Spain, Turkey, UK and USA).

A total of 381 participants were randomized and received at least one dose of study drug.

Participant milestones

Participant milestones
Measure	Mitiperstat Participants received an oral tablet of mitiperstat 5mg once daily.	Placebo Participants receive an oral tablet of placebo matched to mitiperstat once daily.
Overall Study STARTED	189	192
Overall Study Treated	189	192
Overall Study COMPLETED	165	170
Overall Study NOT COMPLETED	24	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Mitiperstat Participants received an oral tablet of mitiperstat 5mg once daily.	Placebo Participants receive an oral tablet of placebo matched to mitiperstat once daily.
Overall Study Adverse Event	11	7
Overall Study Death	1	0
Overall Study Lost to Follow-up	1	1
Overall Study Physician Decision	1	2
Overall Study Protocol Violation	1	1
Overall Study Withdrawal by Subject	3	7
Overall Study Reason not specified	6	4

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Mitiperstat n=189 Participants Participants received an oral tablet of mitiperstat 5mg once daily.	Placebo n=192 Participants Participants receive an oral tablet of placebo matched to mitiperstat once daily.	Total n=381 Participants Total of all reporting groups
Age, Continuous	66.2 Years STANDARD_DEVIATION 6.65 • n=5 Participants	65.7 Years STANDARD_DEVIATION 7.03 • n=7 Participants	66 Years STANDARD_DEVIATION 6.84 • n=5 Participants
Sex: Female, Male Female	77 Participants n=5 Participants	74 Participants n=7 Participants	151 Participants n=5 Participants
Sex: Female, Male Male	112 Participants n=5 Participants	118 Participants n=7 Participants	230 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	26 Participants n=5 Participants	27 Participants n=7 Participants	53 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	163 Participants n=5 Participants	165 Participants n=7 Participants	328 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	182 Participants n=5 Participants	183 Participants n=7 Participants	365 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants

PRIMARY outcome

Timeframe: From baseline to up to 24 weeks

Population: Full Analysis Set (FAS) included all randomised participants who received at least one dose of study intervention. 'While on treatment' estimand strategy was followed, which means that if an intercurrent event occurs all subsequent data for that subject was excluded from the evaluation.

Outcome measures

Outcome measures
Measure	Mitiperstat n=189 Participants Participants received an oral tablet of mitiperstat 5mg once daily.	Placebo n=192 Participants Participants receive an oral tablet of placebo matched to mitiperstat once daily.
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.	125 Participants	125 Participants

SECONDARY outcome

Timeframe: At week 12

Population: The PK set included all participants who had received mitiperstat and had evaluable PK data for mitiperstat, with no important protocol deviations that were thought to have impacted the analysis of the PK data.

Measurement of Time to Reach Maximum Plasma Concentration (Tmax) at pre-randomisation (baseline visit) and week 12.

Outcome measures

Outcome measures
Measure	Mitiperstat n=36 Participants Participants received an oral tablet of mitiperstat 5mg once daily.	Placebo Participants receive an oral tablet of placebo matched to mitiperstat once daily.
To Assess the PK of Mitiperstat (AZD4831) in Patients With Moderate to Severe COPD	1.292 hours Interval 0.42 to 2.92	—

SECONDARY outcome

Timeframe: At week 12

Measurement of Maximum Plasma Concentration (Cmax) at pre-randomisation (baseline visit) and week 12.

Outcome measures

Outcome measures
Measure	Mitiperstat n=36 Participants Participants received an oral tablet of mitiperstat 5mg once daily.	Placebo Participants receive an oral tablet of placebo matched to mitiperstat once daily.
To Assess the Pharmacokinetics (PK) of Mitiperstat (AZD4831) in Patients With Moderate to Severe COPD.	38.786 nmol/L Geometric Coefficient of Variation 39.5	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Mitiperstat n=189 Participants Participants received an oral tablet of mitiperstat 5mg once daily.	Placebo n=192 Participants Participants receive an oral tablet of placebo matched to mitiperstat once daily.
To Evaluate the Effect of Mitiperstat (AZD4831) as Compared to Placebo on the Time to First Moderate or Severe Exacerbation.	53 Participants	44 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Mitiperstat n=130 Participants Participants received an oral tablet of mitiperstat 5mg once daily.	Placebo n=136 Participants Participants receive an oral tablet of placebo matched to mitiperstat once daily.
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.	-0.049 Litre Standard Error 0.0178	-0.031 Litre Standard Error 0.0175

SECONDARY outcome

Timeframe: From baseline to week 12 and week 24

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. It has a theoretical range of 0 to 100, with higher values indicating a more severe condition. The EXACT will be performed at on-site visits using the e-Diary.

Outcome measures

Outcome measures
Measure	Mitiperstat n=122 Participants Participants received an oral tablet of mitiperstat 5mg once daily.	Placebo n=126 Participants Participants receive an oral tablet of placebo matched to mitiperstat once daily.
To Assess the Effect of Mitiperstat (AZD4831) Compared to Placebo on Respiratory Symptoms in Patients With Moderate to Severe COPD. Week 12	0.1 Units on a scale Standard Error 0.97	-2.4 Units on a scale Standard Error 0.95
To Assess the Effect of Mitiperstat (AZD4831) Compared to Placebo on Respiratory Symptoms in Patients With Moderate to Severe COPD. Week 24	-1.9 Units on a scale Standard Error 1.32	-3.7 Units on a scale Standard Error 1.36

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Mitiperstat n=139 Participants Participants received an oral tablet of mitiperstat 5mg once daily.	Placebo n=147 Participants Participants receive an oral tablet of placebo matched to mitiperstat once daily.
To Assess the Effect of Mitiperstat (AZD4831) Compared to Placebo on Respiratory Symptoms in Patients With Moderate to Severe COPD. Week 12	0.16 Units on a scale Standard Error 0.130	0.15 Units on a scale Standard Error 0.127
To Assess the Effect of Mitiperstat (AZD4831) Compared to Placebo on Respiratory Symptoms in Patients With Moderate to Severe COPD. Week 24	0.11 Units on a scale Standard Error 0.166	-0.17 Units on a scale Standard Error 0.172

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Mitiperstat n=159 Participants Participants received an oral tablet of mitiperstat 5mg once daily.	Placebo n=165 Participants Participants receive an oral tablet of placebo matched to mitiperstat once daily.
To Assess the Effect of Mitiperstat (AZD4831) Compared to Placebo in Disease Impact in Patients With Moderate to Severe COPD. Week 12	-1.25 Units on a scale Standard Error 1.183	-3.05 Units on a scale Standard Error 1.160
To Assess the Effect of Mitiperstat (AZD4831) Compared to Placebo in Disease Impact in Patients With Moderate to Severe COPD. Week 24	-2.64 Units on a scale Standard Error 1.540	-3.48 Units on a scale Standard Error 1.562

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Mitiperstat n=134 Participants Participants received an oral tablet of mitiperstat 5mg once daily.	Placebo n=134 Participants Participants receive an oral tablet of placebo matched to mitiperstat once daily.
Change From Baseline to Week 12 in Total COPD Assessment Test (CAT)	-1.2 Units on a scale Standard Error 0.62	-1.2 Units on a scale Standard Error 0.64

Adverse Events

Mitiperstat

Serious events: 23 serious events

Other events: 53 other events

Deaths: 1 deaths

Placebo

Serious events: 13 serious events

Other events: 45 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Mitiperstat n=189 participants at risk Participants received an oral tablet of mitiperstat 5mg once daily.	Placebo n=192 participants at risk Participants receive an oral tablet of placebo matched to mitiperstat once daily.
Infections and infestations Tuberculosis	0.00% 0/189 • From Day 1 to Week 24	0.52% 1/192 • Number of events 1 • From Day 1 to Week 24
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Carcinoid tumour pulmonary	0.00% 0/189 • From Day 1 to Week 24	0.52% 1/192 • Number of events 1 • From Day 1 to Week 24
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.53% 1/189 • Number of events 1 • From Day 1 to Week 24	0.52% 1/192 • Number of events 1 • From Day 1 to Week 24
Nervous system disorders Carotid artery thrombosis	0.53% 1/189 • Number of events 1 • From Day 1 to Week 24	0.00% 0/192 • From Day 1 to Week 24
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	7.4% 14/189 • Number of events 14 • From Day 1 to Week 24	2.6% 5/192 • Number of events 5 • From Day 1 to Week 24
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/189 • From Day 1 to Week 24	0.52% 1/192 • Number of events 1 • From Day 1 to Week 24
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/189 • From Day 1 to Week 24	1.0% 2/192 • Number of events 2 • From Day 1 to Week 24
Respiratory, thoracic and mediastinal disorders Pulmonary mass	0.00% 0/189 • From Day 1 to Week 24	0.52% 1/192 • Number of events 1 • From Day 1 to Week 24
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.53% 1/189 • Number of events 1 • From Day 1 to Week 24	0.00% 0/192 • From Day 1 to Week 24
Vascular disorders Aortic aneurysm	0.53% 1/189 • Number of events 1 • From Day 1 to Week 24	0.00% 0/192 • From Day 1 to Week 24
Cardiac disorders Atrial fibrillation	0.53% 1/189 • Number of events 1 • From Day 1 to Week 24	0.00% 0/192 • From Day 1 to Week 24
Cardiac disorders Cardiac failure acute	0.53% 1/189 • Number of events 1 • From Day 1 to Week 24	0.00% 0/192 • From Day 1 to Week 24
Gastrointestinal disorders Constipation	0.53% 1/189 • Number of events 1 • From Day 1 to Week 24	0.00% 0/192 • From Day 1 to Week 24
Hepatobiliary disorders Cholecystitis acute	0.53% 1/189 • Number of events 1 • From Day 1 to Week 24	0.00% 0/192 • From Day 1 to Week 24
Hepatobiliary disorders Portal hypertension	0.53% 1/189 • Number of events 1 • From Day 1 to Week 24	0.00% 0/192 • From Day 1 to Week 24
Infections and infestations Infective exacerbation of chronic obstructive airways disease	0.00% 0/189 • From Day 1 to Week 24	0.52% 1/192 • Number of events 1 • From Day 1 to Week 24
Infections and infestations Pneumonia	2.6% 5/189 • Number of events 5 • From Day 1 to Week 24	1.6% 3/192 • Number of events 3 • From Day 1 to Week 24

Other adverse events

Other adverse events
Measure	Mitiperstat n=189 participants at risk Participants received an oral tablet of mitiperstat 5mg once daily.	Placebo n=192 participants at risk Participants receive an oral tablet of placebo matched to mitiperstat once daily.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	23.8% 45/189 • Number of events 62 • From Day 1 to Week 24	18.8% 36/192 • Number of events 55 • From Day 1 to Week 24
Infections and infestations Nasopharyngitis	5.8% 11/189 • Number of events 11 • From Day 1 to Week 24	6.2% 12/192 • Number of events 14 • From Day 1 to Week 24

Additional Information

Global Clinical Lead

AstraZeneca Clinical Study Information Center

Phone: +1-877-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee AstraZeneca has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.
Publication restrictions are in place

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