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

AstraZeneca137 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

137

Conditions

Chronic Obstructive Pulmonary Disease (COPD)Chronic Bronchitis

Interventions

TozorakimabDRUG

Participants will receive SC injection of tozorakimab as stated in arm description.

PlaceboOTHER

Participants will receive SC injection of placebo as stated in arm description.

Eligibility

Sex: ALLMin age: 40 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Provision of informed consent. * Participant must be 40 to 80 years of age inclusive, at the time of signing the informed consent form (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 study visit 1 (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 inhaled corticosteroids (ICS) + long-acting beta 2 agonist (LABA) or LABA + long-acting muscarinic receptor antagonist (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/m\^2 (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 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at screening. Participants with mild or asymptomatic disease could be rescreened. * 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 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 human immunodeficiency virus (HIV). * Evidence of active or untreated latent tuberculosis (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 clinical study protocol (CSP). * Inability to perform technically acceptable spirometry. Additional inclusion and exclusion criteria's applies.

Locations (90)

Outcomes

Primary Outcomes

Change From Baseline to Week 12 in Pre-bronchodilator Forced Expiratory Volume in 1 Second (Pre-BD FEV1) as Measured in Clinic

The mean change from baseline in Pre-BD FEV1 at Week 12 (tozorakimab - placebo) estimated using a repeated measures mixed effects analysis of covariance measures was estimated. Data available from all visits up to and including Week 12, irrespective of whether the participant discontinued study drug or received reliever therapy was considered. FEV1 was measured by spirometry at clinic.

Time frame: Baseline (Day -35 to Day -28) through Week 12

Secondary Outcomes

Serum Tozorakimab Concentration

Serum concentration of tozorakimab collected over time are reported. The lower limit of quantification (LLOQ) for tozorakimab was considered to be 10 μg/L.

Time frame: Post-dose at Study Weeks 2, 4, 12, 20, 24, 28, 32, and 36

Number of Participants With Positive Anti-drug Antibodies (ADA) to Tozorakimab

Number of participants with positive ADA to tozorakimab are reported. Treatment-induced ADA positive is defined as ADA negative at baseline and positive at post-baseline assessment. Treatment-boosted ADA positive is defined as ADA positive at baseline and boosted (\>= 4 fold) the pre-existing titre during the study period. Persistent positive is defined as ADA negative at baseline and positive at \>= 2 post-baseline assessments (with \>= 16 weeks between first and last positive) or ADA positive at last post-baseline assessment. Transiently positive is defined as ADA negative at baseline and at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive.

Time frame: Pre-dose at Study Weeks 0 (baseline) and post-dose at Study Weeks 2, 4, 12, 20, 24, 28, 32, and 36

Number of Participants Experiencing First Chronic Obstructive Pulmonary Disease Composite Exacerbations (COPDCompEx) Event

The COPDCompEx combines exacerbations with 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.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Research Site

Sheffield, Alabama, United States

Research Site

Newport Beach, California, United States

Research Site

Newark, Delaware, United States

Research Site

Kissimmee, Florida, United States

Research Site

Ormond Beach, Florida, United States

Research Site

Winter Park, Florida, United States

Research Site

Lakeside Park, Kentucky, United States

Research Site

White Marsh, Maryland, United States

Research Site

Ann Arbor, Michigan, United States

Research Site

New Bern, North Carolina, United States

...and 80 more locations

Time frame: Baseline (Day -35 to Day -28) through Week 28

Change From Baseline to Week 12 in 4-weekly Mean Evaluating Respiratory Symptoms of COPD (E-RS:COPD) Total Score

Change from baseline to Week 12 in 4-weekly mean E-RS:COPD total score is reported. The E-RS™:COPD is an 11-item electronic patient reported outcome (ePRO) questionnaires developed to evaluate the severity of respiratory symptoms of COPD including breathlessness (5 items; score range: 0 to 17), cough and sputum (3 items; score range: 0 to 11), and chest symptoms (3 items; score range: 0 to 12). The ePRO was completed every day at home and at site visits. Summation of E-RS:COPD item responses produced a total score ranging from 0 to 40, with higher scores indicating greater severity. The 4-weekly mean will be calculated as the sum of all non-missing daily scores over the 28-day evaluation period, divided by the number of non-missing daily scores.