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

Chronic Obstructive Pulmonary Disease (COPD) Clinical Trial

— FRONTIER-4  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04631016
• Other study ID #: D9180C00002
• Secondary ID: 2020-000571-20
• Status: Completed
• Phase: Phase 2
• Start date: December 14, 2020
• Est. completion date: November 13, 2023

Study information

• Verified date: April 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 136
• Est. completion date: November 13, 2023
• Est. primary completion date: May 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Disease
• Bronchitis
• Bronchitis, Chronic
• Chronic Bronchitis
• Chronic Obstructive Pulmonary Disease (COPD)
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Biological:
• MEDI3506
Dose 1

Other:
• Placebo
Dose 1

Locations

Country	Name	City	State
Australia	Research Site	Nedlands
Australia	Research Site	South Brisbane
Australia	Research Site	Spearwood
Australia	Research Site	Tarragindi
Canada	Research Site	Ajax	Ontario
Canada	Research Site	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Sherbrooke	Quebec
Canada	Research Site	St. John's	Newfoundland and Labrador
Canada	Research Site	Trois-Rivières	Quebec
Czechia	Research Site	Brno
Czechia	Research Site	Olomouc
Czechia	Research Site	Pisek
Czechia	Research Site	Praha 4
Czechia	Research Site	Rokycany
Denmark	Research Site	Ålborg
Denmark	Research Site	Hvidovre
Denmark	Research Site	København NV
Denmark	Research Site	Naestved
Denmark	Research Site	Odense C
Germany	Research Site	Bamberg
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Darmstadt
Germany	Research Site	Hannover
Germany	Research Site	Leipzig
Germany	Research Site	Mainz
Germany	Research Site	Marburg
Hungary	Research Site	Balassagyarmat
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Edelény
Hungary	Research Site	Gödöllo
Hungary	Research Site	Hajdúnánás
Hungary	Research Site	Pécs
Israel	Research Site	Ashkelon
Israel	Research Site	Jerusalem
Israel	Research Site	Jerusalem
Israel	Research Site	Rehovot
Netherlands	Research Site	Eindhoven
Netherlands	Research Site	Rotterdam
Netherlands	Research Site	Zutphen
New Zealand	Research Site	Auckland
New Zealand	Research Site	Christchurch
New Zealand	Research Site	Tauranga
New Zealand	Research Site	Wellington
Poland	Research Site	Bialystok
Poland	Research Site	Bydgoszcz
Poland	Research Site	Katowice
Poland	Research Site	Krakow
Poland	Research Site	Poznan
Poland	Research Site	Tarnów
Poland	Research Site	Wroclaw
South Africa	Research Site	Cape Town
South Africa	Research Site	Durban
South Africa	Research Site	Johannesburg
South Africa	Research Site	Tygervalley
Spain	Research Site	Alzira
Spain	Research Site	Madrid
Spain	Research Site	Málaga
Spain	Research Site	Mérida
Spain	Research Site	Salamanca
Spain	Research Site	Santander
Spain	Research Site	Zaragoza
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taipei City
Taiwan	Research Site	Taipei City
Taiwan	Research Site	Taoyuan City
United Kingdom	Research Site	Bradford
United Kingdom	Research Site	Bristol
United Kingdom	Research Site	Edinburgh
United Kingdom	Research Site	London
United Kingdom	Research Site	Newcastle-Upon-Tyne
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Boerne	Texas
United States	Research Site	Columbus	Ohio
United States	Research Site	Kissimmee	Florida
United States	Research Site	Lakeside Park	Kentucky
United States	Research Site	New Bern	North Carolina
United States	Research Site	Newark	Delaware
United States	Research Site	Newport Beach	California
United States	Research Site	North Charleston	South Carolina
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Ormond Beach	Florida
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Sheffield	Alabama
United States	Research Site	Spartanburg	South Carolina
United States	Research Site	White Marsh	Maryland
United States	Research Site	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Czechia,  Denmark,  Germany,  Hungary,  Israel,  Netherlands,  New Zealand,  Poland,  South Africa,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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