Clinical trial NCT04631016: A Phase II, Randomized, Double-blind, Placebo-controlled Study to Assess MEDI3506 in Participants With COPD and Chronic Bronchitis
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Obstructive Pulmonary Disease (COPD)
Chronic Bronchitis
Keywords: MEDI3506
IL-33
COPD
Chronic Bronchitis
Lung function
Inflammation
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2020-11-16
Enrollment: 137
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomised to recieve either MEDI3506 or placebo.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline to Week 12 in Pre-bronchodilator Forced Expiratory Volume in 1 Second (Pre-BD FEV1) as Measured in Clinic
timeFrame: Baseline (Day -35 to Day -28) through Week 12
Secondary outcomes:
measure: Serum Tozorakimab Concentration
timeFrame: Post-dose at Study Weeks 2, 4, 12, 20, 24, 28, 32, and 36
measure: Number of Participants With Positive Anti-drug Antibodies (ADA) to Tozorakimab
timeFrame: Pre-dose at Study Weeks 0 (baseline) and post-dose at Study Weeks 2, 4, 12, 20, 24, 28, 32, and 36
measure: Number of Participants Experiencing First Chronic Obstructive Pulmonary Disease Composite Exacerbations (COPDCompEx) Event
timeFrame: Baseline (Day -35 to Day -28) through Week 28
measure: Change From Baseline to Week 12 in 4-weekly Mean Evaluating Respiratory Symptoms of COPD (E-RS:COPD) Total Score
timeFrame: Baseline (from evening of Study Day -14 to the morning of Study Day 1) through Week 12
measure: Change From Baseline to Week 12 in Mean Breathlessness, Cough and Sputum Scale (BCSS) Score (Over the Previous 4 Weeks)
timeFrame: Baseline (from evening of Study Day -14 to the morning of Study Day 1) through Week 12
measure: Change From Baseline to Week 12 in Cough Visual Analogue Scale (VAS) Score
timeFrame: Baseline (from evening of Study Day -14 to the morning of Study Day 1) through Week 12
measure: Change From Baseline to Week 12 in Saint George's Respiratory Questionnaire (SGRQ) Total Score
timeFrame: Baseline (from evening of Study Day -14 to the morning of Study Day 1) through Week 12
measure: Percentage of Participants With a Decrease in SGRQ Total Score of >= 4 Points From Baseline to Week 12
timeFrame: Baseline (from evening of Study Day -14 to the morning of Study Day 1) through Week 12
measure: Change From Baseline to Week 12 in Airwave Oscillometry (AO) Parameters
timeFrame: Baseline (Study Day 1) and Week 12
measure: Change From Baseline to Week 12 in AO Parameter-Area Under the Reactance Curve (AX)
timeFrame: Baseline (Study Day 1) and Week 12
measure: Ratio to Baseline in Daily, Night-time, and Awake Time Cough Frequency at Week 12
timeFrame: Baseline (Day -21 to Day -7) and Week 12
measure: Change From Baseline in Pre-BD FEV1 and Post-BD FEV1 Through Week 28 in Participants With Extent of Emphysema < 10%
timeFrame: Baseline (Week -5 to -4) through Week 28 post-dose
measure: Change From Baseline in Pre-BD FEV1 and Post-BD FEV1 Through Week 28 in Participants With Extent of Emphysema >= 10%
timeFrame: Baseline (Week -5 to -4) through Week 28 post-dose
measure: Change From Baseline in Pre-BD and Post-BD Forced Vital Capacity (FVC) Through Week 28 in Participants With Extent of Emphysema < 10%
timeFrame: Baseline (Week -5 to -4) through Week 28 post-dose
measure: Change From Baseline in Pre-BD and Post-BD FVC Through Week 28 in Participants With Extent of Emphysema >= 10%
timeFrame: Baseline (Week -5 to -4) through Week 28 post-dose
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), and TEAEs of Special Interest (TEAESIs)
timeFrame: Day 1 through 253 days (maximum observed duration)
measure: Number of Participants With Abnormal Vital Signs Reported as TEAEs
timeFrame: Day 1 through 253 days (maximum observed duration)
measure: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
timeFrame: Day 1 through 253 days (maximum observed duration)
measure: Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs
timeFrame: Day 1 through 253 days (maximum observed duration)
measure: Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Measured by Echocardiogram
timeFrame: Baseline (Week -3 to -1) through Week 28
measure: Change From Baseline in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) Level
timeFrame: Baseline (Day -35 to Day -28) through Week 28
measure: Number of Participants With Coronavirus Disease 2019 (COVID-19) Related AEs and SAEs
timeFrame: Day 1 through 253 days (maximum observed duration)
measure: Number of Participants Seropositive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
timeFrame: Baseline (Week 0) through Week 28
Other outcomes:
measure: Change From Baseline in Post-BD FEV1 To Weeks 12 and 28
timeFrame: Baseline (Week -5 to -4) to Weeks 12 and 28 post-dose
Locations:
city: Sheffield
country: United States
facility: Research Site
state: Alabama
city: Newport Beach
country: United States
facility: Research Site
state: California
city: Newark
country: United States
facility: Research Site
state: Delaware
city: Kissimmee
country: United States
facility: Research Site
state: Florida
city: Ormond Beach
country: United States
facility: Research Site
state: Florida
city: Winter Park
country: United States
facility: Research Site
state: Florida
city: Lakeside Park
country: United States
facility: Research Site
state: Kentucky
city: White Marsh
country: United States
facility: Research Site
state: Maryland
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: New Bern
country: United States
facility: Research Site
state: North Carolina
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Oklahoma City
country: United States
facility: Research Site
state: Oklahoma
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: North Charleston
country: United States
facility: Research Site
state: South Carolina
city: Spartanburg
country: United States
facility: Research Site
state: South Carolina
city: Boerne
country: United States
facility: Research Site
state: Texas
city: Nedlands
country: Australia
facility: Research Site
city: South Brisbane
country: Australia
facility: Research Site
city: Spearwood
country: Australia
facility: Research Site
city: Tarragindi
country: Australia
facility: Research Site
city: St. John's
country: Canada
facility: Research Site
state: Newfoundland and Labrador
city: Ajax
country: Canada
facility: Research Site
state: Ontario
city: Sherbrooke
country: Canada
facility: Research Site
state: Quebec
city: Trois-Rivières
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Quebec
country: Canada
facility: Research Site
city: Brno
country: Czechia
facility: Research Site
city: Olomouc
country: Czechia
facility: Research Site
city: Pisek
country: Czechia
facility: Research Site
city: Praha 4
country: Czechia
facility: Research Site
city: Rokycany
country: Czechia
facility: Research Site
city: Hvidovre
country: Denmark
facility: Research Site
city: København NV
country: Denmark
facility: Research Site
city: Naestved
country: Denmark
facility: Research Site
city: Odense C
country: Denmark
facility: Research Site
city: Ålborg
country: Denmark
facility: Research Site
city: Bamberg
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Darmstadt
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Mainz
country: Germany
facility: Research Site
city: Marburg
country: Germany
facility: Research Site
city: Balassagyarmat
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Edelény
country: Hungary
facility: Research Site
city: Gödöllő
country: Hungary
facility: Research Site
city: Hajdúnánás
country: Hungary
facility: Research Site
city: Pécs
country: Hungary
facility: Research Site
city: Ashkelon
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Rehovot
country: Israel
facility: Research Site
city: Eindhoven
country: Netherlands
facility: Research Site
city: Rotterdam
country: Netherlands
facility: Research Site
city: Zutphen
country: Netherlands
facility: Research Site
city: Auckland
country: New Zealand
facility: Research Site
city: Christchurch
country: New Zealand
facility: Research Site
city: Tauranga
country: New Zealand
facility: Research Site
city: Wellington
country: New Zealand
facility: Research Site
city: Białystok
country: Poland
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Katowice
country: Poland
facility: Research Site
city: Krakow
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Tarnów
country: Poland
facility: Research Site
city: Wroclaw
country: Poland
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Durban
country: South Africa
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
city: Tygervalley
country: South Africa
facility: Research Site
city: Alzira
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Málaga
country: Spain
facility: Research Site
city: Mérida
country: Spain
facility: Research Site
city: Salamanca
country: Spain
facility: Research Site
city: Santander
country: Spain
facility: Research Site
city: Zaragoza
country: Spain
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: Taoyuan City
country: Taiwan
facility: Research Site
city: Bradford
country: United Kingdom
facility: Research Site
city: Bristol
country: United Kingdom
facility: Research Site
city: Edinburgh
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Research Site
Study officials:
References: