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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04631016




Registration number
NCT04631016
Ethics application status
Date submitted
20/10/2020
Date registered
16/11/2020

Titles & IDs
Public title
A Phase II, Randomized, Double-blind, Placebo-controlled Study to Assess MEDI3506 in Participants With COPD and Chronic Bronchitis
Scientific 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)
Secondary ID [1] 0 0
2020-000571-20
Secondary ID [2] 0 0
D9180C00002
Universal Trial Number (UTN)
Trial acronym
FRONTIER-4
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Obstructive Pulmonary Disease (COPD) 0 0
Chronic Bronchitis 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Infection 0 0 0 0
Other infectious diseases
Respiratory 0 0 0 0
Chronic obstructive pulmonary disease
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tozorakimab
Other interventions - Placebo

Experimental: Tozorakimab - Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).

Placebo comparator: Placebo - Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.


Treatment: Drugs: Tozorakimab
Participants will receive SC injection of tozorakimab as stated in arm description.

Other interventions: Placebo
Participants will receive SC injection of placebo as stated in arm description.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline to Week 12 in Pre-bronchodilator Forced Expiratory Volume in 1 Second (Pre-BD FEV1) as Measured in Clinic
Timepoint [1] 0 0
Baseline (Day -35 to Day -28) through Week 12
Secondary outcome [1] 0 0
Serum Tozorakimab Concentration
Timepoint [1] 0 0
Post-dose at Study Weeks 2, 4, 12, 20, 24, 28, 32, and 36
Secondary outcome [2] 0 0
Number of Participants With Positive Anti-drug Antibodies (ADA) to Tozorakimab
Timepoint [2] 0 0
Pre-dose at Study Weeks 0 (baseline) and post-dose at Study Weeks 2, 4, 12, 20, 24, 28, 32, and 36
Secondary outcome [3] 0 0
Number of Participants Experiencing First Chronic Obstructive Pulmonary Disease Composite Exacerbations (COPDCompEx) Event
Timepoint [3] 0 0
Baseline (Day -35 to Day -28) through Week 28
Secondary outcome [4] 0 0
Change From Baseline to Week 12 in 4-weekly Mean Evaluating Respiratory Symptoms of COPD (E-RS:COPD) Total Score
Timepoint [4] 0 0
Baseline (from evening of Study Day -14 to the morning of Study Day 1) through Week 12
Secondary outcome [5] 0 0
Change From Baseline to Week 12 in Mean Breathlessness, Cough and Sputum Scale (BCSS) Score (Over the Previous 4 Weeks)
Timepoint [5] 0 0
Baseline (from evening of Study Day -14 to the morning of Study Day 1) through Week 12
Secondary outcome [6] 0 0
Change From Baseline to Week 12 in Cough Visual Analogue Scale (VAS) Score
Timepoint [6] 0 0
Baseline (from evening of Study Day -14 to the morning of Study Day 1) through Week 12
Secondary outcome [7] 0 0
Change From Baseline to Week 12 in Saint George's Respiratory Questionnaire (SGRQ) Total Score
Timepoint [7] 0 0
Baseline (from evening of Study Day -14 to the morning of Study Day 1) through Week 12
Secondary outcome [8] 0 0
Percentage of Participants With a Decrease in SGRQ Total Score of >= 4 Points From Baseline to Week 12
Timepoint [8] 0 0
Baseline (from evening of Study Day -14 to the morning of Study Day 1) through Week 12
Secondary outcome [9] 0 0
Change From Baseline to Week 12 in Airwave Oscillometry (AO) Parameters
Timepoint [9] 0 0
Baseline (Study Day 1) and Week 12
Secondary outcome [10] 0 0
Change From Baseline to Week 12 in AO Parameter-Area Under the Reactance Curve (AX)
Timepoint [10] 0 0
Baseline (Study Day 1) and Week 12
Secondary outcome [11] 0 0
Ratio to Baseline in Daily, Night-time, and Awake Time Cough Frequency at Week 12
Timepoint [11] 0 0
Baseline (Day -21 to Day -7) and Week 12
Secondary outcome [12] 0 0
Change From Baseline in Pre-BD FEV1 and Post-BD FEV1 Through Week 28 in Participants With Extent of Emphysema < 10%
Timepoint [12] 0 0
Baseline (Week -5 to -4) through Week 28 post-dose
Secondary outcome [13] 0 0
Change From Baseline in Pre-BD FEV1 and Post-BD FEV1 Through Week 28 in Participants With Extent of Emphysema >= 10%
Timepoint [13] 0 0
Baseline (Week -5 to -4) through Week 28 post-dose
Secondary outcome [14] 0 0
Change From Baseline in Pre-BD and Post-BD Forced Vital Capacity (FVC) Through Week 28 in Participants With Extent of Emphysema < 10%
Timepoint [14] 0 0
Baseline (Week -5 to -4) through Week 28 post-dose
Secondary outcome [15] 0 0
Change From Baseline in Pre-BD and Post-BD FVC Through Week 28 in Participants With Extent of Emphysema >= 10%
Timepoint [15] 0 0
Baseline (Week -5 to -4) through Week 28 post-dose
Secondary outcome [16] 0 0
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), and TEAEs of Special Interest (TEAESIs)
Timepoint [16] 0 0
Day 1 through 253 days (maximum observed duration)
Secondary outcome [17] 0 0
Number of Participants With Abnormal Vital Signs Reported as TEAEs
Timepoint [17] 0 0
Day 1 through 253 days (maximum observed duration)
Secondary outcome [18] 0 0
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Timepoint [18] 0 0
Day 1 through 253 days (maximum observed duration)
Secondary outcome [19] 0 0
Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs
Timepoint [19] 0 0
Day 1 through 253 days (maximum observed duration)
Secondary outcome [20] 0 0
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Measured by Echocardiogram
Timepoint [20] 0 0
Baseline (Week -3 to -1) through Week 28
Secondary outcome [21] 0 0
Change From Baseline in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) Level
Timepoint [21] 0 0
Baseline (Day -35 to Day -28) through Week 28
Secondary outcome [22] 0 0
Number of Participants With Coronavirus Disease 2019 (COVID-19) Related AEs and SAEs
Timepoint [22] 0 0
Day 1 through 253 days (maximum observed duration)
Secondary outcome [23] 0 0
Number of Participants Seropositive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Timepoint [23] 0 0
Baseline (Week 0) through Week 28

Eligibility
Key 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.
Minimum age
40 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/12/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
13/11/2023
Sample size
Target
Accrual to date
Final
137
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Nedlands
Recruitment hospital [2] 0 0
Research Site - South Brisbane
Recruitment hospital [3] 0 0
Research Site - Spearwood
Recruitment hospital [4] 0 0
Research Site - Tarragindi
Recruitment postcode(s) [1] 0 0
6009 - Nedlands
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
6163 - Spearwood
Recruitment postcode(s) [4] 0 0
4121 - Tarragindi
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Delaware
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Kentucky
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Oklahoma
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
South Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
Canada
State/province [14] 0 0
Newfoundland and Labrador
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
Canada
State/province [16] 0 0
Quebec
Country [17] 0 0
Czechia
State/province [17] 0 0
Brno
Country [18] 0 0
Czechia
State/province [18] 0 0
Olomouc
Country [19] 0 0
Czechia
State/province [19] 0 0
Pisek
Country [20] 0 0
Czechia
State/province [20] 0 0
Praha 4
Country [21] 0 0
Czechia
State/province [21] 0 0
Rokycany
Country [22] 0 0
Denmark
State/province [22] 0 0
Hvidovre
Country [23] 0 0
Denmark
State/province [23] 0 0
København NV
Country [24] 0 0
Denmark
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Naestved
Country [25] 0 0
Denmark
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Odense C
Country [26] 0 0
Denmark
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Ålborg
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Germany
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Bamberg
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Germany
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Berlin
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Germany
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Darmstadt
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Germany
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Hannover
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Germany
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Leipzig
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Germany
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Mainz
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Germany
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Marburg
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Hungary
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Balassagyarmat
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Hungary
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Budapest
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Hungary
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Debrecen
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Hungary
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Edelény
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Hungary
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Gödöllo
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Hungary
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Hajdúnánás
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Hungary
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Pécs
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Israel
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Ashkelon
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Israel
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Jerusalem
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Israel
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Rehovot
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Netherlands
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Eindhoven
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Rotterdam
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Netherlands
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Zutphen
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New Zealand
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Auckland
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New Zealand
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Christchurch
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New Zealand
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Tauranga
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New Zealand
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Wellington
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Poland
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Bialystok
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Poland
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Bydgoszcz
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Poland
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Katowice
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Krakow
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Poznan
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Tarnów
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Poland
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Wroclaw
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South Africa
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Cape Town
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South Africa
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Durban
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South Africa
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Johannesburg
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South Africa
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Tygervalley
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Spain
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Alzira
Country [63] 0 0
Spain
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Madrid
Country [64] 0 0
Spain
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Málaga
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Spain
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Mérida
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Spain
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Salamanca
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Spain
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Santander
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Spain
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Zaragoza
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Taiwan
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Kaohsiung
Country [70] 0 0
Taiwan
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Taipei City
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Taiwan
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Taoyuan City
Country [72] 0 0
United Kingdom
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Bradford
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United Kingdom
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Bristol
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United Kingdom
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Edinburgh
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United Kingdom
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London
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United Kingdom
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Newcastle-Upon-Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04631016