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

• ClinicalTrials.gov Identifier: NCT05492877
• Recruitment Status: Active, not recruiting
• First Posted: August 9, 2022
• Last Update Posted: May 13, 2024
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: July 22, 2022
• First Posted Date: August 9, 2022
• Last Update Posted Date: May 13, 2024
• Actual Study Start Date: November 14, 2022
• Estimated Primary Completion Date: August 16, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 5, 2023)

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. [ Time Frame: From baseline to up to 24 weeks ]

All patients randomised to either active or placebo arm.

Original Primary Outcome Measures (submitted: August 5, 2022)

To evaluate the effect of AZD4831 as compared to placebo on the time to first COPD Composite Exacerbation (CompEx) event. [ Time Frame: From baseline to up to 24 weeks ]

All participants randomised to either active or placebo arm.

Current Secondary Outcome Measures (submitted: June 5, 2023)

• To assess the pharmacokinetics (PK) of mitiperstat (AZD4831) in patients with moderate to severe COPD. [ Time Frame: 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 mitiperstat (AZD4831) in patients with moderate to severe COPD [ Time Frame: 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 mitiperstat (AZD4831) as compared to placebo on the time to first moderate or severe exacerbation. [ Time Frame: 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. [ Time Frame: From baseline to week 12 ]
  All patients randomised to either active or placebo arms. Change in post-BD FEV1.
• To assess the effect of mitiperstat (AZD4831) compared to placebo on respiratory symptoms in patients with moderate to severe COPD. [ Time Frame: From baseline to week 12 and week 24 ]
  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.
• To assess the effect of mitiperstat (AZD4831) compared to placebo on respiratory symptoms in patients with moderate to severe COPD. [ Time Frame: From baseline to week 12 and week 24 ]
  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).
• To assess the effect of mitiperstat (AZD4831) compared to placebo on respiratory symptoms in patients with moderate to severe COPD. [ Time Frame: 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. [ Time Frame: 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).

Original Secondary Outcome Measures (submitted: August 5, 2022)

• To assess the pharmacokinetics (PK) of AZD4831 in participants with moderate to severe COPD. [ Time Frame: 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 [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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 [ Time Frame: 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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: An Efficacy and Safety Study of Mitiperstat (AZD4831) (MPO Inhibitor) vs Placebo in the Treatment of Moderate to Severe COPD.
• 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)
• 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 Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Participants will be randomised to receive either Mitiperstat (AZD4831) or placebo.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

• Condition: Chronic Obstructive Pulmonary Disease (COPD)

Intervention

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

Study Arms

• Placebo Comparator: Placebo
  Approximately 203 participants will be randomised to receive placebo.
  Intervention: Other: Placebo
• Experimental: Mitiperstat (AZD4831)
  Approximately 203 participants will be randomised to receive mitiperstat (AZD4831).
  Intervention: Drug: Mitiperstat (AZD4831)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 10, 2024): 380
• Original Estimated Enrollment (submitted: August 5, 2022): 288
• Estimated Study Completion Date: August 16, 2024
• Estimated Primary Completion Date: August 16, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Bulgaria, Canada, Denmark, Germany, Italy, Mexico, Netherlands, Poland, South Africa, Spain, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT05492877
• Other Study ID Numbers: D6582C00001; 2022-002441-18 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: AstraZeneca
• Original Responsible Party: Same as current
• Current Study Sponsor: AstraZeneca
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: AstraZeneca
• Verification Date: May 2024