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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03809663




Registration number
NCT03809663
Ethics application status
Date submitted
10/01/2019
Date registered
18/01/2019

Titles & IDs
Public title
A Dose Ranging Placebo-Controlled Double-Blind Study to Evaluate the Safety and Efficacy of Tezepelumab in Atopic Dermatitis
Scientific title
A Dose-Ranging, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Tezepelumab Alone or Combined With Topical Corticosteroids in Moderate-to-Severe Atopic Dermatitis
Secondary ID [1] 0 0
2018-001997-52
Secondary ID [2] 0 0
20170755
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atopic Dermatitis 0 0
Condition category
Condition code
Skin 0 0 0 0
Dermatological conditions
Skin 0 0 0 0
Other skin conditions
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

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

Placebo comparator: Part A: Placebo - Matching placebo administered via SC injection Q2W for a maximum of 52 weeks.

Participants defined as non-responders (those who do not achieve at least 50% improvement in EASI at Week 16 compared to baseline) will switch to receive tezepelumab 420 mg SC injection Q2W for the remainder of the study beginning with the Week 18 dose.

Experimental: Part A: Tezepelumab 210 mg - Tezepelumab 210 mg administered via SC injection once every 4 weeks (Q4W) from Week 4 for a maximum of 52 weeks.

All participants randomized to tezepelumab will receive 420 mg SC injection as their first dose. Participants will then receive a placebo at Week 2 to maintain blinding.

Participants defined as non-responders (those who do not achieve at least 50% improvement in EASI at Week 16 compared to baseline) will switch to receive tezepelumab 420 mg SC injection Q2W for the remainder of the study beginning with the Week 18 dose.

Experimental: Part A: Tezepelumab 280 mg - Tezepelumab 280 mg administered via SC injection Q2W from Week 2 for a maximum of 52 weeks.

All participants randomized to tezepelumab will receive 420 mg SC injection as their first dose. Participants will then receive their randomized dose of 280 mg Q2W from Week 2.

Participants defined as non-responders (those who did not achieve at least 50% improvement in EASI at Week 16 compared to baseline) will switch to receive tezepelumab 420 mg SC injection Q2W for the remainder of the study beginning with the Week 18 dose.

Experimental: Part A: Tezepelumab 420 mg - Tezepelumab 420 mg administered via SC injection Q2W for a maximum of 52 weeks.

Experimental: Part B: Placebo and Topical Corticosteroids Regimen - Matching placebo administered via SC injection Q2W with topical corticosteroids (TCS) for a maximum of 52 weeks.

Experimental: Part B: Tezepelumab 420 mg and Topical Corticosteroids Regimen - Tezepelumab 420 mg administered via SC injection Q2W with TCS for a maximum of 52 weeks.


Treatment: Drugs: Tezepelumab
Solution for injection

Other interventions: Placebo
Placebo solution for injection
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
Number of Participants With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) (IGA 0/1) at Week 16
Timepoint [1] 0 0
Week 16
Primary outcome [2] 0 0
Number of Participants Who Experienced a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI 75) at Week 16
Timepoint [2] 0 0
Baseline and Week 16
Secondary outcome [1] 0 0
Number of Participants Who Experienced a 50% or 90% Reduction From Baseline in Eczema Area and Severity Index (EASI 50/90) at Week 16
Timepoint [1] 0 0
Baseline and Week 16
Secondary outcome [2] 0 0
Time to Achievement of 50%, 75% or 90% Reduction From Day 1 in Eczema Area and Severity Index (EASI 50/75/90)
Timepoint [2] 0 0
Day 1 up to End of Study Visit (Week 70)
Secondary outcome [3] 0 0
Change From Baseline in Scoring of Atopic Dermatitis (SCORAD) at Week 16
Timepoint [3] 0 0
Baseline and Week 16
Secondary outcome [4] 0 0
Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 16
Timepoint [4] 0 0
Baseline and Week 16
Secondary outcome [5] 0 0
Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration
Timepoint [5] 0 0
Pre-dose on Day 1, Week 2, 4, 12, 16, 24, 32, 40, 48, 50, 52, 58 and 70
Secondary outcome [6] 0 0
Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16
Timepoint [6] 0 0
Pre-dose on Week 24, 32, 40, 48, 50, 52, 58 and 70

Eligibility
Key inclusion criteria
* Subject has provided informed consent prior to initiation of any study specific activities/procedures.
* Age greater than or equal to 18 to less than or equal to 75 years at screening.
* Clinical diagnosis of chronic AD (also known as atopic eczema) for at least 2 years prior to screening and has confirmed AD (Hanifin and Rajka criteria for AD (Hanifin and Rajka, 1980).
* AD that affects greater than or equal to' 10% body surface area as assessed by EASI at screening and on day 1.
* An IGA score of greater than or equal to 3 at screening and on day 1.
* An EASI score of greater than or equal to 16 at screening and on day 1.
* Subject discontinued treatment with TCS, topical calcineurin inhibitors (TCI), and prescription moisturizers containing TCS or topical calcineurin inhibitors (TCI) for at least the 7 days immediately prior to the first dose of investigational product
* Documented recent history (within 12 months before the screening visit) of inadequate response totreatment with topical TCS or subjects for whom topical treatments are otherwise medically inadvisable (ie, because of important side effects or safety risks).

* Inadequate response is defined as failure to achieve and maintain remission or a low disease activity state (comparable to IGA 0 = clear to IGA 2 = mild) despite treatment with a daily regimen of TCS of medium or higher potency (with or without TCI as appropriate).
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Active dermatologic conditions, which might confound the diagnosis of AD or would interfere with the assessment of treatment, such as scabies, seborrheic dermatitis, cutaneous lymphoma, ichthyosis, psoriasis, allergic contact dermatitis, or irritant contact dermatitis.
* History of a clinically significant infection within 28 days prior to day 1 that, in the opinion of the investigator or medical monitor, might compromise the safety of the subject in the study, interfere with evaluation of the investigational product, or reduce the subject's ability to participate in the study. Clinically significant infections are defined as either of the following: 1) a systemic infection; or 2) a serious skin infection requiring parenteral antibiotic, antiviral, or antifungal medication.
* Diagnosis of a helminth parasitic infection within 6 months prior to screening that had not been treated with or had failed to respond to standard of care therapy.
* Documented medical history of chronic alcohol or drug abuse within 12 months prior to screening.
* History of anaphylaxis following any biologic therapy.
* Evidence of active liver disease at screening, including jaundice or aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase greater than twice the upper limit of normal (ULN).
* Subjects who, in the opinion of the investigator, have evidence of active tuberculosis (TB), either treated or untreated, or a positive QuantiFERON-tuberculosis Gold (QFT-G) test for TB during screening. Subjects with an indeterminate QFT-G may be enrolled if they have ALL of the following:

* No symptoms of TB: productive, prolonged cough (> 3 weeks); coughing up blood; fever; night sweats; unexplained appetite loss; unintentional weight loss
* No evidence of active TB on chest radiograph within 3 months prior to the first dose of investigational product. Note: Chest radiograph is not part of screening procedure and will be the responsibility
* Positive hepatitis B surface antigen or hepatitis C antibody serology. Subjects with a history of hepatitis B vaccination without a history of hepatitis B are allowed to enroll in the study.
* Positive human immunodeficiency virus (HIV) test at screening or the subject is taking antiretroviral medications, as determined by medical history, prior medications, and/or the subject's verbal report.
* Other Medical Conditions>
* History of malignancy, except for basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy = 12 months prior to screening or other malignancies treated with apparent success with curative therapy = 5 years prior to screening.
* History or evidence of severe depression, schizophrenia, previous suicide attempts, or suicidal ideation.

Prior/Concomitant Therapy:

* Subjects who are unwilling to abstain from the use of TCS, TCI, and prescription moisturizers (those that contain TCS and TCI) from screening through week 16 (applies only to Part A subjects)
* Subjects who have had side effects of topical medications including intolerance to treatment, hypersensitivity reactions, significant skin atrophy, or systemic effects as assessed by the investigator or by the subject's treating physician (applies only to Part B subjects)
* More than or equal to 30% of the total lesional surface is located on areas of thin skin that cannot be safely treated with medium or higher potency TCS (eg, face, neck, intertriginous areas, areas of skin atrophy) (applies only to Part B subjects)
* Receipt of any approved biologic agent (eg, dupilumab) within 4 months or 5 elimination half-lives (whichever is longer) prior to screening
* Have used immunosuppressive/immunomodulating drugs (eg, systemic corticosteroids, cyclosporine, mycophenolate-mofetil, interferon (IFN)-gamma, Janus kinase inhibitors, azathioprine, methotrexate) within 4 weeks prior to screening, or any condition that, in the opinion of the investigator, is likely to require such treatment(s) during the first 4 weeks of study treatment.
* Have had phototherapy for AD in the 2 months prior to day 1, and subjects unwilling to avoid phototherapy during the first 16 weeks of the study
* If on allergen-specific immunotherapy, subjects must be on a maintenance dose and schedule for = 28 days prior to screening. Allergen-specific immunotherapy is defined as SC immunotherapy to aeroallergens and/o venom (Hymenoptera) as well as sublingual immunotherapy to aeroallergens
* Vaccination with a live or attenuated vaccine within 28 days prior to day 1. Receipt of inactive/killed vaccinations (eg, inactive influenza) is allowed. Note that receipt of the Th2 cytokine inhibitor suplatast within 15 days prior to randomization and during the study is not allowed.
* Major surgery within 8 weeks prior to screening or planned inpatient surgery or hospitalization during the study period
* Currently receiving treatment in another investigational device or drug study, or less than 6 months since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.

Other Exclusions:

* Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 16 weeks after the last dose of investigational product. (Females of childbearing potential should only be enrolled in the study after a negative highly sensitive serum pregnancy test).
* Female subjects of childbearing potential who are sexually active with unsterilized male partners unwilling to use 1 highly effective method of contraception during treatment and for an additional 16 weeks after the last dose of investigational product. Cessation of contraception after this point must be discussed with a responsible physician. Females of childbearing potential are defined as those who are not surgically sterile (ie, had bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause). A highly effective method of contraception is defined as one that resulted in a low failure rate (ie, < 1% per year) when used consistently and correctly.
* Subject has known sensitivity to any of the products or components to be administered during dosing.
* History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.

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
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/03/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
22/12/2020
Sample size
Target
Accrual to date
Final
251
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Holdsworth House Medical Practice - Sydney
Recruitment hospital [2] 0 0
Veracity Clinical Research - Woolloongabba
Recruitment hospital [3] 0 0
Skin Health Institute - Carlton
Recruitment hospital [4] 0 0
The Royal Melbourne Hospital - Parkville
Recruitment hospital [5] 0 0
Fremantle Dermatology - Fremantle
Recruitment postcode(s) [1] 0 0
2010 - Sydney
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
3053 - Carlton
Recruitment postcode(s) [4] 0 0
3050 - Parkville
Recruitment postcode(s) [5] 0 0
6160 - Fremantle
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Kansas
Country [6] 0 0
United States of America
State/province [6] 0 0
Kentucky
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
Nevada
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
Tennessee
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington
Country [13] 0 0
Canada
State/province [13] 0 0
British Columbia
Country [14] 0 0
Canada
State/province [14] 0 0
Ontario
Country [15] 0 0
Czechia
State/province [15] 0 0
Brno
Country [16] 0 0
Czechia
State/province [16] 0 0
Novy Jicin
Country [17] 0 0
Czechia
State/province [17] 0 0
Ostrava-Poruba
Country [18] 0 0
Czechia
State/province [18] 0 0
Praha 1
Country [19] 0 0
Czechia
State/province [19] 0 0
Praha 8
Country [20] 0 0
Estonia
State/province [20] 0 0
Tallinn
Country [21] 0 0
Estonia
State/province [21] 0 0
Tartu
Country [22] 0 0
Germany
State/province [22] 0 0
Berlin
Country [23] 0 0
Germany
State/province [23] 0 0
Göttingen
Country [24] 0 0
Germany
State/province [24] 0 0
Hannover
Country [25] 0 0
Hungary
State/province [25] 0 0
Budapest
Country [26] 0 0
Hungary
State/province [26] 0 0
Debrecen
Country [27] 0 0
Hungary
State/province [27] 0 0
Miskolc
Country [28] 0 0
Hungary
State/province [28] 0 0
Pecs
Country [29] 0 0
Hungary
State/province [29] 0 0
Szeged
Country [30] 0 0
Japan
State/province [30] 0 0
Chiba
Country [31] 0 0
Japan
State/province [31] 0 0
Fukuoka
Country [32] 0 0
Japan
State/province [32] 0 0
Hokkaido
Country [33] 0 0
Japan
State/province [33] 0 0
Hyogo
Country [34] 0 0
Japan
State/province [34] 0 0
Nagasaki
Country [35] 0 0
Japan
State/province [35] 0 0
Osaka
Country [36] 0 0
Japan
State/province [36] 0 0
Tokyo
Country [37] 0 0
Japan
State/province [37] 0 0
Toyama
Country [38] 0 0
Korea, Republic of
State/province [38] 0 0
Seoul
Country [39] 0 0
Latvia
State/province [39] 0 0
Riga
Country [40] 0 0
Latvia
State/province [40] 0 0
Ventspils
Country [41] 0 0
Poland
State/province [41] 0 0
Gdansk
Country [42] 0 0
Poland
State/province [42] 0 0
Lodz
Country [43] 0 0
Poland
State/province [43] 0 0
Lublin
Country [44] 0 0
Poland
State/province [44] 0 0
Swidnik
Country [45] 0 0
Poland
State/province [45] 0 0
Warszawa
Country [46] 0 0
Poland
State/province [46] 0 0
Wroclaw
Country [47] 0 0
Spain
State/province [47] 0 0
AndalucÃ-a
Country [48] 0 0
Spain
State/province [48] 0 0
Cataluña
Country [49] 0 0
Spain
State/province [49] 0 0
Comunidad Valenciana
Country [50] 0 0
Spain
State/province [50] 0 0
Madrid
Country [51] 0 0
Switzerland
State/province [51] 0 0
Lausanne
Country [52] 0 0
Ukraine
State/province [52] 0 0
Chernivtsi
Country [53] 0 0
Ukraine
State/province [53] 0 0
Dnipro
Country [54] 0 0
Ukraine
State/province [54] 0 0
Ivano-Frankivsk
Country [55] 0 0
Ukraine
State/province [55] 0 0
Kyiv
Country [56] 0 0
Ukraine
State/province [56] 0 0
Uzhhorod
Country [57] 0 0
Ukraine
State/province [57] 0 0
Zaporizhzhia
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Dundee
Country [59] 0 0
United Kingdom
State/province [59] 0 0
London
Country [60] 0 0
United Kingdom
State/province [60] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amgen
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
AstraZeneca
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
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?
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Available to whom?
Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.amgen.com/datasharing


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03809663