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

Sponsor

AstraZeneca (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05492877

Collaborator

(none)

288

Enrollment

Arms

17.2

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This is a research study to evaluate the efficacy and safety of the investigational drug AZD4831 in adult participants with chronic obstructive pulmonary disease.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease (COPD)	Drug: AZD4831 Other: Placebo	Phase 2

Detailed Description

Study D6582C00001 is a phase IIa randomised, double blind placebo controlled, parallel arm study to evaluate the efficacy and safety of AZD4831 in adult participants with moderate to severe chronic obstructive pulmonary disease.

Approximately 74 sites globally will participate in this study. Approximately 288 participants will be randomised to two treatment groups (AZD4831 vs placebo) in a 1:1 ratio.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

288 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Participants will be randomised to receive either AZD4831 or placebo.Participants will be randomised to receive either AZD4831 or placebo.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase 2a Randomised, Double Blind, Placebo Controlled, Parallel Arm, Multi-Centre Study to Evaluate the Efficacy and Safety of AZD4831 in Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

Anticipated Study Start Date :

Nov 6, 2022

Anticipated Primary Completion Date :

Apr 12, 2024

Anticipated Study Completion Date :

Apr 12, 2024

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Approximately 144 participants will be randomised to receive placebo.	Other: Placebo Oral dosage, once daily.
Experimental: AZD4831 Approximately 144 participants will be randomised to receive AZD4831.	Drug: AZD4831 Oral dosage, once daily.

Arm

Intervention/Treatment

Placebo Comparator: Placebo

Approximately 144 participants will be randomised to receive placebo.

Other: Placebo

Oral dosage, once daily.

Experimental: AZD4831

Approximately 144 participants will be randomised to receive AZD4831.

Drug: AZD4831

Oral dosage, once daily.

Outcome Measures

Primary Outcome Measures

To evaluate the effect of AZD4831 as compared to placebo on the time to first COPD Composite Exacerbation (CompEx) event. [From baseline to up to 24 weeks]
All participants randomised to either active or placebo arm.

Secondary Outcome Measures

To assess the pharmacokinetics (PK) of AZD4831 in participants 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 assess the PK of AZD4831 in participants 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).
To evaluate the effect of AZD4831 as compared to placebo on the time to first moderate or severe exacerbation. [From baseline to up to week 24]
All participants randomised to either active or placebo arms.
To assess the effects of AZD4831 as compared to placebo on post-bronchodilator (BD) forced expiratory volume in the first second (FEV1) in participants with moderate to severe COPD. [From baseline to week 12]
All participants randomised to either active or placebo arms. Change in post-BD FEV1.
To assess the effect of AZD4831 compared to placebo on respiratory symptoms in participants with moderate to severe COPD. [From baseline to week 12 and week 24]
All participants randomised to either active or placebo arms. Change from baseline in Evaluating Respiratory Symptoms: Chronic Obstructive Pulmonary Disease scale (E-RS:COPD scale) where an overall score represents overall respiratory symptom severity, and 3 subscales assess breathlessness, cough and sputum, and chest-related symptoms respectively.
To assess the effect of AZD4831 compared to placebo on respiratory symptoms in participants with moderate to severe COPD. [From baseline to week 12 and week 24]
All participants 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).
To assess the effect of AZD4831 compared to placebo on respiratory symptoms in participants with moderate to severe COPD. [From baseline to week 12 and week 24]
All participants 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 AZD4831 compared to placebo in disease impact in participants with moderate to severe COPD. [From baseline to Week 12]
All participants 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 effects of AZD4831 compared to placebo on change in cough frequency measured over a 24-hour period [From baseline to week 12]
Change from baseline in average 24-hour, waking and sleeping cough frequency, using the VitaloJAK Cough Monitor device at week 12.

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

Participants with a positive diagnostic lateral flow test for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) at Study Visit 1 (SV1) or Study Visit 3 (SV3).
Participants with a significant Coronavirus Disease 2019 (COVID-19) illness within 6 months of enrolment.
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.