A Phase II, Randomized, Double-blind, Placebo-controlled Study to Assess MEDI3506 in Participants With COPD and Chronic Bronchitis

Study Overview
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Brief Summary
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This is a research study to determine the efficacy and safety of investigational drug MEDI3506 for the treatment of adult subjects with Chronic Obstructive Pulmonary Disease and Chronic Bronchitis.

Detailed Description
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Study D9180C00002 is a Phase II, randomised, double-blind, placebo-controlled, parallel group, proof of concept study to evaluate the efficacy and safety of MEDI3506 in adult participants with moderate to severe Chronic Obstructive Pulmonary Disease and Chronic Bronchitis. Approximately 85 sites globally will participate in this study. Approximately 144 participants will be randomized to 2 treatment groups in a 1:1 ratio to receive MEDI3506 or placebo.

Official Title
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A Phase II, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Safety and Tolerability of MEDI3506 in Participants With Moderate to Severe Chronic Obstructive Pulmonary Disease and Chronic Bronchitis (FRONTIER 4)

Conditions
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Chronic Obstructive Pulmonary Disease (COPD), Chronic Bronchitis

Intervention / Treatment
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* Biological: MEDI3506
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of informed consent Participant must be 40 to 80 years of age inclusive, at the time of signing the ICF.. Participants who are current or ex-smokers with a tobacco history of ≥ 10 pack-years. Participants who have a documented history of COPD for at least 1 year. Participants who have a post-BD FEV1/FVC < 0.70 and a post-BD FEV1 >= 20% and < 80% predicted normal value at screening. Centralized spirometry will be used for this criteria assessment. Participants who have a physician confirmed participant history of chronic bronchitis as defined as presence of cough and sputum on most days for ≥ 3 months/year in at least the 2 year period immediately prior to SV1(Screening) Participants who have an average BCSS score of ≥ 2 in cough and ≥ 2 in sputum domains assessed over 14 days preceding SV3 Participants who have a documented stable regimen of dual therapy or triple therapy for ≥ 3 months prior to enrolment; there should have been no change in treatment after the previous exacerbation prior to entering into the study. Where dual therapy consists of ICS + LABA or LABA + LAMA, and triple therapy consists of ICS + LABA + LAMA. Participants who have a documented history of ≥ 1 moderate or severe AECOPD requiring systemic corticosteroids and/or antibiotics for at least 3 days duration (or 1 injection of depot formulation), or hospitalization for reason of AECOPD in the previous 24 months. Body mass index within the range 18 to 40 kg/m2 (inclusive). Female participants of childbearing potential, must have negative pregnancy tests. Male and female participants must follow protocol contraceptive guidance. Exclusion Criteria: Participants with a positive diagnostic nucleic acid test for SARS-CoV-2 at screening. Subjects with mild or asymptomatic disease could be rescreened. Participants with a significant 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 which in the investigator's opinion makes it undesirable for the participant to participate in the study. Current or past diagnosis of asthma which persisted beyond age of 25 years Clinically important pulmonary disease other than COPD, radiological findings, and/or laboratory findings suggestive of a respiratory disease other than COPD that is contributing to the participant's respiratory symptoms. Increased pre-BD FEV1 at randomization visit (SV3) compared to Screening SV1 of ≥ 400 mL or ≥ 25% of SV1 FEV1. Any other clinically relevant abnormal findings on physical examination, laboratory testing; or chest CT scan, 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. Chest CT scan findings requiring further investigation or repeat CT surveillance before SV14 A family history of heart failure. A LVEF < 45% measured by echocardiogram. History of a clinically significant infection (viral, bacterial, or fungal) within 4 weeks. History of, or a reason to believe a participant has a history of, drug or alcohol abuse within the past 2 years prior to screening. Participants with a recent history of, or who have a positive test for, infective hepatitis or unexplained jaundice, or participants who have been treated for hepatitis B, hepatitis C, or HIV. Evidence of active or untreated latent TB. Change in smoking status in 12 weeks prior to enrolment or intention to change smoking status between enrolment and end of follow-up. Participants currently receiving background therapy that is not approved by regulatory authorities in the country of study for COPD are not eligible for the study. History of treatment with cardiotoxic medications (eg, as part of cancer therapy) including thiazolidinedione's. Treatment with broad spectrum antibiotic within 4 weeks prior to randomization (Day 1). Receiving any of the prohibited concomitant medications as specified in the CSP. Inability to perform technically acceptable spirometry. Additional inclusion and exclusion criteria's applies

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomised to recieve either MEDI3506 or placebo.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MEDI3506<br>Approximately 72 participants will be randomized to receive MEDI3506 | Biological: MEDI3506<br>* Dose 1<br>|
| Placebo Comparator: Placebo<br>Approximately 72 participants will be randomized to receive placebo | Other: Placebo<br>* Dose 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to Week 12 in pre-bronchdilator forced expiratory volume in 1 second (FEV1) measured in clinic. | To assess the effects of MEDI3506 compared with placebo on pulmonary function in participants with COPD and chronic bronchitis. | From Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the PK concentration- time curve, during the intervention and follow up periods. | To assess the PK of MEDI3506 in participants with COPD and chronic bronchitis. | From Study Day 1 to Week 36 | 
| Peak plasma concentration (Cmax) profile during the intervention and follow up periods | To assess the PK of MEDI3506 in participants with COPD and chronic bronchitis. | From Study Day 1 to Week 36 | 
| Anti-drug antibodies during the intervention and follow-up periods. | To assess the immunogenicity of MEDI3506 compared with placebo in participants with COPD and chronic bronchitis. | From Study Day 1 to Week 36 | 
| Time to first COPDCompEx event based on the period from baseline to 4 weeks after last dose (Week 28) | To assess the effect of MEDI3506 on COPDCompEx event in participants with COPD and chronic bronchitis | From Baseline to Week 28 | 
| Change from baseline to Week 12 in E-RS:COPD | To assess the effect of MEDI3506 compared with placebo on respiratory symptoms in participants with COPD and chronic bronchitis. Higher score indicates worse outcome. Min Score = 0 Max Score= 40 | From Baseline to Week 12 | 
| Change from baseline to Week 12 in Mean Breathless, cough and sputum scale (BCSS) Score | To assess the effect of MEDI3506 compared with placebo on respiratory symptoms in participants with COPD and chronic bronchitis. Higher score indicates worse outcome. Min Score= 0 Max Score=12 | From Baseline to Week 12 | 
| Change from baseline to Week 12 in Cough Visual Analogue Scale (VAS) item | To assess the effect of MEDI3506 compared with placebo on respiratory symptoms in participants with COPD and chronic bronchitis. Higher score indicates worse outcome. Min Score= 0 Max Score=100 | From Baseline to Week 12 | 
| Change from baseline to Week 12 in St Georges Respiratory Questionnaire (SGRQ) total score | To assess the effect of MEDI3506 compared with placebo on disease impact in participants with COPD and chronic bronchitis. Higher score indicates worse outcome. Min Score= 0 Max Score=100 | From Baseline to Week 12 | 
| Proportion of participants with a decrease in St Georges Respiratory Questionnaire (SGRQ) total score of ≥ 4 points from baseline to Week 12 | To assess the effect of MEDI3506 compared with placebo on disease impact in participants with COPD and chronic bronchitis. Responder endpoint 'yes' and 'no'. 'No' is the worse outcome. | From Baseline to Week 12 | 
| Change from baseline to Week 12 in Airway Oscillometry parameter difference between R5 and R20 (R5-R20) | To assess the effect of MEDI3506 compared with placebo on airway resistance and reactance in participants with COPD and chronic bronchitis. | From Baseline to Week 12 | 
| Change from baseline to Week 12 in Airway Oscillometry parameter Area under Reactance Curve (AX). | To assess the effect of MEDI3506 compared with placebo on airway resistance and reactance in participants with COPD and chronic bronchitis. | From Baseline to Week 12 | 
| Change from baseline to Week 12 in Airway Oscillometry parameter resistance at 20Hz (R20) . | To assess the effect of MEDI3506 compared with placebo on airway resistance and reactance in participants with COPD and chronic bronchitis. | From Baseline to Week 12 | 
| Change from baseline to Week 12 in Airway Oscillometry parameter resistance at 5Hz (R5) | To assess the effect of MEDI3506 compared with placebo on airway resistance and reactance in participants with COPD and chronic bronchitis. | From Baseline to Week 12 | 
| At Week 12, ratio to baseline in: Daily (ie, 24 hour) cough frequency, Night time cough frequency, Awake time cough frequency | To evaluate the effect of MEDI3506 compared with placebo on objective cough measures in participants with COPD and chronic bronchitis. | Week 12 | 
| Change from baseline in pre-BD and post-BD FEV1 through Week 28 | To evaluate the effect of MEDI3506 or placebo on lung function by extent of baseline emphysema on CT scan | From Baseline to Week 28 | 
| Change from baseline in pre-BD and post BD FVC through Week 28 | To evaluate the effect of MEDI3506 or placebo on lung function by extent of baseline emphysema on CT scan | From Baseline to Week 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MEDI3506, IL-33, COPD, Chronic Bronchitis, Lung function, Inflammation