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

Chronic Obstructive Pulmonary Disease (COPD) Clinical Trial

— CRESCENDO  

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05492877
• Other study ID #: D6582C00001
• Secondary ID: 2022-002441-18
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 14, 2022
• Est. completion date: August 16, 2024

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 380
• Est. completion date: August 16, 2024
• Est. primary completion date: August 16, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease (COPD)
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Mitiperstat (AZD4831)
Oral dosage, once daily.

Other:
• Placebo
Oral dosage, once daily.

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Córdoba
Argentina	Research Site	Ranelagh
Argentina	Research Site	San Fernando
Bulgaria	Research Site	Dupnitsa
Bulgaria	Research Site	Haskovo
Bulgaria	Research Site	Pernik
Bulgaria	Research Site	Ruse
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Stara Zagora
Bulgaria	Research Site	Stara Zagora
Bulgaria	Research Site	Vratsa
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Quebec
Canada	Research Site	Quebec
Canada	Research Site	St Charles Borromee	Quebec
Canada	Research Site	Trois-Rivières	Quebec
Denmark	Research Site	Aalborg
Denmark	Research Site	Hvidovre
Denmark	Research Site	København NV
Denmark	Research Site	Næstved
Denmark	Research Site	Odense C
Denmark	Research Site	Vejle
Germany	Research Site	Berlin
Germany	Research Site	Frankfurt
Germany	Research Site	Immenhausen
Germany	Research Site	Koblenz
Germany	Research Site	Landsberg
Germany	Research Site	Leipzig
Germany	Research Site	Marburg
Germany	Research Site	Witten
Italy	Research Site	Foggia
Italy	Research Site	Roma
Italy	Research Site	Sassari
Italy	Research Site	Siena
Italy	Research Site	Verona
Mexico	Research Site	Culiacán
Mexico	Research Site	Guadalajara
Mexico	Research Site	Monterrey
Mexico	Research Site	Monterrey
Mexico	Research Site	Veracruz
Mexico	Research Site	Zapopan
Netherlands	Research Site	Groningen
Netherlands	Research Site	Veldhoven
Poland	Research Site	Bielsko-Biala
Poland	Research Site	Checiny
Poland	Research Site	Karczew
Poland	Research Site	Kraków
Poland	Research Site	Ksawerów
Poland	Research Site	Staszów
Poland	Research Site	Szczecin
Poland	Research Site	Warszawa
South Africa	Research Site	Cape Town
South Africa	Research Site	Durban
South Africa	Research Site	Durban
South Africa	Research Site	Tygervalley
South Africa	Research Site	Vereeniging
Spain	Research Site	Granada
Spain	Research Site	Madrid
Spain	Research Site	Málaga
Spain	Research Site	Merida
Spain	Research Site	Santander
Turkey	Research Site	Adana
Turkey	Research Site	Ankara
Turkey	Research Site	Istanbul
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
Turkey	Research Site	Mersin
United Kingdom	Research Site	Bradford
United Kingdom	Research Site	Cambridge
United Kingdom	Research Site	Cottingham
United Kingdom	Research Site	Dundee
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Nottingham
United Kingdom	Research Site	Rotherham
United Kingdom	Research Site	Salford
United Kingdom	Research Site	Wakefield
United Kingdom	Research Site	York
United States	Research Site	Amarillo	Texas
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Chesterfield	Missouri
United States	Research Site	Chicago Ridge	Illinois
United States	Research Site	Choctaw	Oklahoma
United States	Research Site	Clearwater	Florida
United States	Research Site	Columbus	Ohio
United States	Research Site	DeLand	Florida
United States	Research Site	Fort Mill	South Carolina
United States	Research Site	Gastonia	North Carolina
United States	Research Site	Kernersville	North Carolina
United States	Research Site	Miami	Florida
United States	Research Site	New Bern	North Carolina
United States	Research Site	New Windsor	New York
United States	Research Site	Newport Beach	California
United States	Research Site	Orlando	Florida
United States	Research Site	Saint Charles	Missouri
United States	Research Site	Tampa	Florida
United States	Research Site	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Argentina,  Bulgaria,  Canada,  Denmark,  Germany,  Italy,  Mexico,  Netherlands,  Poland,  South Africa,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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