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

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)

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.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Other: Placebo; Drug: Mitiperstat (AZD4831)

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 Type: Interventional
• Enrollment (Actual): 381
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1414AIF
    • Research Site
  • Buenos Aires, Argentina, C1121ABE
    • Research Site
  • Buenos Aires, Argentina, C1425BEN
    • Research Site
  • Córdoba, Argentina, X5003DCE
    • Research Site
  • Ranelagh, Argentina, 1886
    • Research Site
  • San Fernando, Argentina, B1646EBJ
    • Research Site
• Bulgaria
  • Dupnitsa, Bulgaria, 2602
    • Research Site
  • Haskovo, Bulgaria, 6305
    • Research Site
  • Pernik, Bulgaria, 2300
    • Research Site
  • Rousse, Bulgaria, 7000
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  • Sofia, Bulgaria, 1756
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  • Stara Zagora, Bulgaria, 6003
    • Research Site
  • Stara Zagora, Bulgaria, 6000
    • Research Site
  • Vratsa, Bulgaria, 3000
    • Research Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 0M3
      • Research Site
  • Quebec
    • Québec, Quebec, Canada, G1V 4G5
      • Research Site
    • Québec, Quebec, Canada, G3K 2P8
      • Research Site
    • Saint-Charles-Borromée, Quebec, Canada, J6E 2B4
      • Research Site
    • Trois-Rivières, Quebec, Canada, G8T 7A1
      • Research Site
• Denmark
  • Aalborg, Denmark, 9000
    • Research Site
  • Hvidovre, Denmark, 2650
    • Research Site
  • København NV, Denmark, 2400
    • Research Site
  • Næstved, Denmark, 4700
    • Research Site
  • Odense C, Denmark, 5000
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  • Vejle, Denmark, 7100
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• Germany
  • Berlin, Germany, 10119
    • Research Site
  • Frankfurt, Germany, 60596
    • Research Site
  • Immenhausen, Germany, 34376
    • Research Site
  • Koblenz, Germany, 56068
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  • Landsberg, Germany, 86899
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  • Leipzig, Germany, 04299
    • Research Site
  • Marburg, Germany, 35037
    • Research Site
  • Witten, Germany, 58452
    • Research Site
• Italy
  • Foggia, Italy, 71100
    • Research Site
  • Roma, Italy, 00168
    • Research Site
  • Sassari, Italy, 07100
    • Research Site
  • Siena, Italy, 53100
    • Research Site
  • Verona, Italy, 37134
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• Mexico
  • Culiacán, Mexico, 80200
    • Research Site
  • Guadalajara, Mexico, 44670
    • Research Site
  • Monterrey, Mexico, 64465
    • Research Site
  • Monterrey, Mexico, 64310
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  • Veracruz, Mexico, 91910
    • Research Site
  • Zapopan, Mexico, 45138
    • Research Site
• Netherlands
  • Groningen, Netherlands, 9713 GH
    • Research Site
  • Veldhoven, Netherlands, 5504 DB
    • Research Site
• Poland
  • Bielsko-Biala, Poland, 43-300
    • Research Site
  • Chęciny, Poland, 26-060
    • Research Site
  • Karczew, Poland, 05-480
    • Research Site
  • Krakow, Poland, 31-011
    • Research Site
  • Ksawerów, Poland, 95-054
    • Research Site
  • Staszów, Poland, 28-200
    • Research Site
  • Szczecin, Poland, 70-111
    • Research Site
  • Warsaw, Poland, 01-456
    • Research Site
• South Africa
  • Cape Town, South Africa, 7700
    • Research Site
  • Durban, South Africa, 4001
    • Research Site
  • Durban, South Africa, 4093
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  • Tygervalley, South Africa, 7530
    • Research Site
  • Vereeniging, South Africa, 1935
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• Spain
  • Granada, Spain, 18014
    • Research Site
  • Madrid, Spain, 28007
    • Research Site
  • Málaga, Spain, 29010
    • Research Site
  • Mérida, Spain, 06800
    • Research Site
  • Santander, Spain, 39008
    • Research Site
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01330
    • Research Site
  • Ankara, Turkey (Türkiye), 06620
    • Research Site
  • Istanbul, Turkey (Türkiye), 34854
    • Research Site
  • Istanbul, Turkey (Türkiye), 34890
    • Research Site
  • Izmir, Turkey (Türkiye), 35360
    • Research Site
  • Mersin, Turkey (Türkiye), 33343
    • Research Site
• United Kingdom
  • Bradford, United Kingdom, BD9 6RJ
    • Research Site
  • Cambridge, United Kingdom, CB2 0QQ
    • Research Site
  • Cottingham, United Kingdom, HU16 5JQ
    • Research Site
  • Dundee, United Kingdom, DD1 9SY
    • Research Site
  • Glasgow, United Kingdom, G12 0YN
    • Research Site
  • London, United Kingdom, NW3 2QG
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  • London, United Kingdom, EC1M 6BQ
    • Research Site
  • Manchester, United Kingdom, M8 5RB
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  • Nottingham, United Kingdom, NG5 1PB
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  • Rotherham, United Kingdom, S65 2QL
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  • Wakefield, United Kingdom, WF1 4DG
    • Research Site
  • York, United Kingdom, YO24 3WX
    • Research Site
• United States
  • California
    • Newport Beach, California, United States, 92663
      • Research Site
  • Florida
    • Clearwater, Florida, United States, 33765
      • Research Site
    • DeLand, Florida, United States, 32720
      • Research Site
    • Miami, Florida, United States, 33186
      • Research Site
    • Orlando, Florida, United States, 32825
      • Research Site
    • Tampa, Florida, United States, 33606
      • Research Site
    • Winter Park, Florida, United States, 32789
      • Research Site
  • Illinois
    • Chicago Ridge, Illinois, United States, 60415
      • Research Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Research Site
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Research Site
    • Saint Charles, Missouri, United States, 63301
      • Research Site
  • New York
    • New Windsor, New York, United States, 12553
      • Research Site
  • North Carolina
    • Gastonia, North Carolina, United States, 28054
      • Research Site
    • Kernersville, North Carolina, United States, 27284
      • Research Site
    • New Bern, North Carolina, United States, 28562
      • Research Site
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Research Site
  • Oklahoma
    • Choctaw, Oklahoma, United States, 73020
      • Research Site
  • South Carolina
    • Fort Mill, South Carolina, United States, 29707
      • Research Site
  • Texas
    • Amarillo, Texas, United States, 79106
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Approximately 203 participants will be randomised to receive placebo.	Other: Placebo; Oral dosage, once daily.
Experimental: Mitiperstat (AZD4831); Approximately 203 participants will be randomised to receive mitiperstat (AZD4831).	Drug: Mitiperstat (AZD4831); Oral dosage, once daily.

What is the study measuring?

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.	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.	From baseline to up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At week 12
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.	At week 12
To Evaluate the Effect of Mitiperstat (AZD4831) as Compared to Placebo on the Time to First Moderate or Severe Exacerbation.	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.	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.	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.	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.	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.	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.	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.	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.	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.	From baseline to week 12 and week 24
Change From Baseline to Week 12 in Total COPD Assessment Test (CAT)	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.	From baseline to Week 12

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• D6582C00001 CSR Synopsis
• D6582C00001 CSP Redacted
• D6582C00001 SAP

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2022
• Primary Completion (Actual): August 12, 2024
• Study Completion (Actual): August 12, 2024

Study Registration Dates

• First Submitted: July 22, 2022
• First Submitted That Met QC Criteria: August 5, 2022
• First Posted (Actual): August 9, 2022

Study Record Updates

• Last Update Posted (Estimated): August 29, 2025
• Last Update Submitted That Met QC Criteria: August 28, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: COPD; Lung function; Chronic Obstructive Pulmonary Disease; AZD4831; Myeloperoxidase; MPO; Myeloperoxidase inhibitor; Mitiperstat
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pathological Conditions, Signs and Symptoms; Pulmonary Disease, Chronic Obstructive; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs; AZD4831
• Other Study ID Numbers: D6582C00001; 2022-002441-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No