A Phase II, Randomized, Double-blind, Placebo-controlled Study to Assess MEDI3506 in Participants With COPD and Chronic Bronchitis (FRONTIER-4)

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)

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.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD); Chronic Bronchitis
• Intervention / Treatment: Biological: MEDI3506; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 136
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Nedlands, Australia, 6009
    • Research Site
  • South Brisbane, Australia, 4101
    • Research Site
  • Spearwood, Australia, 6163
    • Research Site
  • Tarragindi, Australia, 4121
    • Research Site
• Canada
  • Quebec, Canada, G1G 3Y8
    • Research Site
  • Quebec, Canada, G2J 0C4
    • Research Site
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Research Site
  • Ontario
    • Ajax, Ontario, Canada, L1S 2J5
      • Research Site
  • Quebec
    • Sherbrooke, Quebec, Canada, J1L 0H8
      • Research Site
    • Trois-Rivières, Quebec, Canada, G8T 7A1
      • Research Site
• Czechia
  • Brno, Czechia, 625 00
    • Research Site
  • Olomouc, Czechia, 775 21
    • Research Site
  • Pisek, Czechia, 397 01
    • Research Site
  • Praha 4, Czechia, 140 46
    • Research Site
  • Rokycany, Czechia, 337 22
    • Research Site
• Denmark
  • Hvidovre, Denmark, 2650
    • Research Site
  • København NV, Denmark, 2400
    • Research Site
  • Naestved, Denmark, 4700
    • Research Site
  • Odense C, Denmark, 5000
    • Research Site
  • Ålborg, Denmark, 9000
    • Research Site
• Germany
  • Bamberg, Germany, 96049
    • Research Site
  • Berlin, Germany, 10717
    • Research Site
  • Berlin, Germany, 13187
    • Research Site
  • Darmstadt, Germany, 64283
    • Research Site
  • Hannover, Germany, D-30173
    • Research Site
  • Leipzig, Germany, 04107
    • Research Site
  • Mainz, Germany, 55128
    • Research Site
  • Marburg, Germany, 35037
    • Research Site
• Hungary
  • Balassagyarmat, Hungary, 2660
    • Research Site
  • Budapest, Hungary, 1033
    • Research Site
  • Debrecen, Hungary, 4032
    • Research Site
  • Edelény, Hungary, 3780
    • Research Site
  • Gödöllő, Hungary, 2100
    • Research Site
  • Hajdúnánás, Hungary, 4080
    • Research Site
  • Pécs, Hungary, 7635
    • Research Site
• Israel
  • Ashkelon, Israel, 7830604
    • Research Site
  • Jerusalem, Israel, 91031
    • Research Site
  • Jerusalem, Israel, 91120
    • Research Site
  • Rehovot, Israel, 7661041
    • Research Site
• Netherlands
  • Eindhoven, Netherlands, 5623EJ
    • Research Site
  • Rotterdam, Netherlands, 3083 AN
    • Research Site
  • Zutphen, Netherlands, 7207 AE
    • Research Site
• New Zealand
  • Auckland, New Zealand, 0626
    • Research Site
  • Christchurch, New Zealand, 8013
    • Research Site
  • Tauranga, New Zealand, 3110
    • Research Site
  • Wellington, New Zealand, 6021
    • Research Site
• Poland
  • Białystok, Poland, 15-044
    • Research Site
  • Bydgoszcz, Poland, 85-079
    • Research Site
  • Katowice, Poland, 40-648
    • Research Site
  • Krakow, Poland, 31-501
    • Research Site
  • Poznań, Poland, 60-693
    • Research Site
  • Tarnów, Poland, 33-100
    • Research Site
  • Wroclaw, Poland, 54-239
    • Research Site
• South Africa
  • Cape Town, South Africa, 7700
    • Research Site
  • Durban, South Africa, 4001
    • Research Site
  • Johannesburg, South Africa, 2113
    • Research Site
  • Tygervalley, South Africa, 7530
    • Research Site
• Spain
  • Alzira, Spain, 46600
    • Research Site
  • Madrid, Spain, 28007
    • Research Site
  • Málaga, Spain, 29010
    • Research Site
  • Mérida, Spain, 06800
    • Research Site
  • Salamanca, Spain, 37007
    • Research Site
  • Santander, Spain, 39010
    • Research Site
  • Zaragoza, Spain, 50009
    • Research Site
• Taiwan
  • Kaohsiung, Taiwan, 807
    • Research Site
  • Kaohsiung, Taiwan, 83301
    • Research Site
  • Taipei City, Taiwan, 114
    • Research Site
  • Taipei City, Taiwan, 110
    • Research Site
  • Taoyuan City, Taiwan, 333
    • Research Site
• United Kingdom
  • Bradford, United Kingdom, BD9 6RJ
    • Research Site
  • Bristol, United Kingdom, BS105NB
    • Research Site
  • Edinburgh, United Kingdom, EH16 4SA
    • Research Site
  • London, United Kingdom, EC1A 7BE
    • Research Site
  • Newcastle-Upon-Tyne, United Kingdom, NE7 7DN
    • Research Site
• United States
  • Alabama
    • Sheffield, Alabama, United States, 35660
      • Research Site
  • California
    • Newport Beach, California, United States, 92663
      • Research Site
  • Delaware
    • Newark, Delaware, United States, 19713
      • Research Site
  • Florida
    • Kissimmee, Florida, United States, 34746
      • Research Site
    • Ormond Beach, Florida, United States, 32174
      • Research Site
    • Winter Park, Florida, United States, 32789
      • Research Site
  • Kentucky
    • Lakeside Park, Kentucky, United States, 41017
      • Research Site
  • Maryland
    • White Marsh, Maryland, United States, 21162
      • Research Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48197
      • Research Site
  • North Carolina
    • New Bern, North Carolina, United States, 28562
      • Research Site
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Research Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Research Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Research Site
  • South Carolina
    • North Charleston, South Carolina, United States, 29406
      • Research Site
    • Spartanburg, South Carolina, United States, 29303
      • Research Site
  • Texas
    • Boerne, Texas, United States, 78006
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MEDI3506; Approximately 72 participants will be randomized to receive MEDI3506	Biological: MEDI3506; Dose 1
Placebo Comparator: Placebo; Approximately 72 participants will be randomized to receive placebo	Other: Placebo; Dose 1

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2020
• Primary Completion (Actual): May 30, 2023
• Study Completion (Actual): November 13, 2023

Study Registration Dates

• First Submitted: October 20, 2020
• First Submitted That Met QC Criteria: November 10, 2020
• First Posted (Actual): November 16, 2020

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Inflammation; COPD; Lung function; Chronic Bronchitis; MEDI3506; IL-33
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Disease Attributes; Bronchial Diseases; Chronic Disease; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Acute Disease; Bronchitis; Bronchitis, Chronic
• Other Study ID Numbers: D9180C00002; 2020-000571-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No