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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: Other - MEDI3506
Other interventions - Placebo

Experimental: MEDI3506 - Approximately 72 participants will be randomized to receive MEDI3506

Placebo comparator: Placebo - Approximately 72 participants will be randomized to receive placebo


Treatment: Other: MEDI3506
Dose 1

Other interventions: Placebo
Dose 1
Intervention code [1] 0 0
Treatment: Other
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-bronchdilator forced expiratory volume in 1 second (FEV1) measured in clinic.
Timepoint [1] 0 0
From Baseline to Week 12
Secondary outcome [1] 0 0
Area under the PK concentration- time curve, during the intervention and follow up periods.
Timepoint [1] 0 0
From Study Day 1 to Week 36
Secondary outcome [2] 0 0
Peak plasma concentration (Cmax) profile during the intervention and follow up periods
Timepoint [2] 0 0
From Study Day 1 to Week 36
Secondary outcome [3] 0 0
Anti-drug antibodies during the intervention and follow-up periods.
Timepoint [3] 0 0
From Study Day 1 to Week 36
Secondary outcome [4] 0 0
Time to first COPDCompEx event based on the period from baseline to 4 weeks after last dose (Week 28)
Timepoint [4] 0 0
From Baseline to Week 28
Secondary outcome [5] 0 0
Change from baseline to Week 12 in E-RS:COPD
Timepoint [5] 0 0
From Baseline to Week 12
Secondary outcome [6] 0 0
Change from baseline to Week 12 in Mean Breathless, cough and sputum scale (BCSS) Score
Timepoint [6] 0 0
From Baseline to Week 12
Secondary outcome [7] 0 0
Change from baseline to Week 12 in Cough Visual Analogue Scale (VAS) item
Timepoint [7] 0 0
From Baseline to Week 12
Secondary outcome [8] 0 0
Change from baseline to Week 12 in St Georges Respiratory Questionnaire (SGRQ) total score
Timepoint [8] 0 0
From Baseline to Week 12
Secondary outcome [9] 0 0
Proportion of participants with a decrease in St Georges Respiratory Questionnaire (SGRQ) total score of = 4 points from baseline to Week 12
Timepoint [9] 0 0
From Baseline to Week 12
Secondary outcome [10] 0 0
Change from baseline to Week 12 in Airway Oscillometry parameter difference between R5 and R20 (R5-R20)
Timepoint [10] 0 0
From Baseline to Week 12
Secondary outcome [11] 0 0
Change from baseline to Week 12 in Airway Oscillometry parameter Area under Reactance Curve (AX).
Timepoint [11] 0 0
From Baseline to Week 12
Secondary outcome [12] 0 0
Change from baseline to Week 12 in Airway Oscillometry parameter resistance at 20Hz (R20) .
Timepoint [12] 0 0
From Baseline to Week 12
Secondary outcome [13] 0 0
Change from baseline to Week 12 in Airway Oscillometry parameter resistance at 5Hz (R5)
Timepoint [13] 0 0
From Baseline to Week 12
Secondary outcome [14] 0 0
At Week 12, ratio to baseline in: Daily (ie, 24 hour) cough frequency, Night time cough frequency, Awake time cough frequency
Timepoint [14] 0 0
Week 12
Secondary outcome [15] 0 0
Change from baseline in pre-BD and post-BD FEV1 through Week 28
Timepoint [15] 0 0
From Baseline to Week 28
Secondary outcome [16] 0 0
Change from baseline in pre-BD and post BD FVC through Week 28
Timepoint [16] 0 0
From Baseline to 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 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.
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 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 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
136
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
State/province [24] 0 0
Naestved
Country [25] 0 0
Denmark
State/province [25] 0 0
Odense C
Country [26] 0 0
Denmark
State/province [26] 0 0
Ålborg
Country [27] 0 0
Germany
State/province [27] 0 0
Bamberg
Country [28] 0 0
Germany
State/province [28] 0 0
Berlin
Country [29] 0 0
Germany
State/province [29] 0 0
Darmstadt
Country [30] 0 0
Germany
State/province [30] 0 0
Hannover
Country [31] 0 0
Germany
State/province [31] 0 0
Leipzig
Country [32] 0 0
Germany
State/province [32] 0 0
Mainz
Country [33] 0 0
Germany
State/province [33] 0 0
Marburg
Country [34] 0 0
Hungary
State/province [34] 0 0
Balassagyarmat
Country [35] 0 0
Hungary
State/province [35] 0 0
Budapest
Country [36] 0 0
Hungary
State/province [36] 0 0
Debrecen
Country [37] 0 0
Hungary
State/province [37] 0 0
Edelény
Country [38] 0 0
Hungary
State/province [38] 0 0
Gödöllo
Country [39] 0 0
Hungary
State/province [39] 0 0
Hajdúnánás
Country [40] 0 0
Hungary
State/province [40] 0 0
Pécs
Country [41] 0 0
Israel
State/province [41] 0 0
Ashkelon
Country [42] 0 0
Israel
State/province [42] 0 0
Jerusalem
Country [43] 0 0
Israel
State/province [43] 0 0
Rehovot
Country [44] 0 0
Netherlands
State/province [44] 0 0
Eindhoven
Country [45] 0 0
Netherlands
State/province [45] 0 0
Rotterdam
Country [46] 0 0
Netherlands
State/province [46] 0 0
Zutphen
Country [47] 0 0
New Zealand
State/province [47] 0 0
Auckland
Country [48] 0 0
New Zealand
State/province [48] 0 0
Christchurch
Country [49] 0 0
New Zealand
State/province [49] 0 0
Tauranga
Country [50] 0 0
New Zealand
State/province [50] 0 0
Wellington
Country [51] 0 0
Poland
State/province [51] 0 0
Bialystok
Country [52] 0 0
Poland
State/province [52] 0 0
Bydgoszcz
Country [53] 0 0
Poland
State/province [53] 0 0
Katowice
Country [54] 0 0
Poland
State/province [54] 0 0
Krakow
Country [55] 0 0
Poland
State/province [55] 0 0
Poznan
Country [56] 0 0
Poland
State/province [56] 0 0
Tarnów
Country [57] 0 0
Poland
State/province [57] 0 0
Wroclaw
Country [58] 0 0
South Africa
State/province [58] 0 0
Cape Town
Country [59] 0 0
South Africa
State/province [59] 0 0
Durban
Country [60] 0 0
South Africa
State/province [60] 0 0
Johannesburg
Country [61] 0 0
South Africa
State/province [61] 0 0
Tygervalley
Country [62] 0 0
Spain
State/province [62] 0 0
Alzira
Country [63] 0 0
Spain
State/province [63] 0 0
Madrid
Country [64] 0 0
Spain
State/province [64] 0 0
Málaga
Country [65] 0 0
Spain
State/province [65] 0 0
Mérida
Country [66] 0 0
Spain
State/province [66] 0 0
Salamanca
Country [67] 0 0
Spain
State/province [67] 0 0
Santander
Country [68] 0 0
Spain
State/province [68] 0 0
Zaragoza
Country [69] 0 0
Taiwan
State/province [69] 0 0
Kaohsiung
Country [70] 0 0
Taiwan
State/province [70] 0 0
Taipei City
Country [71] 0 0
Taiwan
State/province [71] 0 0
Taoyuan City
Country [72] 0 0
United Kingdom
State/province [72] 0 0
Bradford
Country [73] 0 0
United Kingdom
State/province [73] 0 0
Bristol
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Edinburgh
Country [75] 0 0
United Kingdom
State/province [75] 0 0
London
Country [76] 0 0
United Kingdom
State/province [76] 0 0
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
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04631016