Clinical trial NCT03809663: A Dose Ranging Placebo-Controlled Double-Blind Study to Evaluate the Safety and Efficacy of Tezepelumab in Atopic Dermatitis
Official 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Atopic Dermatitis
Keywords: Atopic Dermatitis
eczema
tezepelumab
dermatology
dermatitis
inflammation
skin
moderate dermatitis
severe dermatitis
Lead sponsor: Amgen
Sponsor class: INDUSTRY
Collaborators: name: AstraZeneca
First posted: 2019-01-18
Enrollment: 251
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This phase 2b study is designed to evaluate the safety and efficacy of tezepelumab as a monotherapy and explore its efficacy as adjunct therapy in subjects with moderate-to-severe AD. This study consists of Part A (the main study evaluating tezepelumab as a monotherapy) and Part B (a study evaluating tezepelumab as adjunctive therapy when combined with a topical corticosteroid regimen
Primary purpose: TREATMENT

Brief summary: This phase 2b study is designed to evaluate the safety and efficacy of tezepelumab as a monotherapy and explore its efficacy as adjunct therapy in subjects with moderate-to-severe atopic dermatitis (AD).

Detailed description: All subjects will receive a subcutaneous (SC) dose of either investigational product or placebo as the first dose on day 1.

Subjects who are determined to be non-responders in Part A will receive tezepelumab SC every 2 weeks (Q2W) following completion of all week 16 study activities. Nonresponders are defined as those subjects who have not achieved at least a 50% improvement in Eczema Area and Severity Index (EASI) at week 16 compared to baseline (day 1).

Safety follow-up is 18 weeks after the end of treatment (EOT) visit (20 weeks after the final dose of investigational product).

Eligibility criteria: 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).

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.

Primary outcomes:
measure: Number of Participants With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) (IGA 0/1) at Week 16
timeFrame: Week 16
measure: Number of Participants Who Experienced a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI 75) at Week 16
timeFrame: Baseline and Week 16
Secondary outcomes:
measure: Number of Participants Who Experienced a 50% or 90% Reduction From Baseline in Eczema Area and Severity Index (EASI 50/90) at Week 16
timeFrame: Baseline and Week 16
measure: Time to Achievement of 50%, 75% or 90% Reduction From Day 1 in Eczema Area and Severity Index (EASI 50/75/90)
timeFrame: Day 1 up to End of Study Visit (Week 70)
measure: Change From Baseline in Scoring of Atopic Dermatitis (SCORAD) at Week 16
timeFrame: Baseline and Week 16
measure: Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 16
timeFrame: Baseline and Week 16
measure: Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration
timeFrame: Pre-dose on Day 1, Week 2, 4, 12, 16, 24, 32, 40, 48, 50, 52, 58 and 70
measure: Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16
timeFrame: Pre-dose on Week 24, 32, 40, 48, 50, 52, 58 and 70
Other outcomes:
Locations:
city: Fountain Valley
country: United States
facility: First OC Dermatology
state: California
city: Santa Monica
country: United States
facility: Clinical Science Institute
state: California
city: Alpharetta
country: United States
facility: Hamilton Research, LLC
state: Georgia
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: West Dundee
country: United States
facility: Dundee Dermatology
state: Illinois
city: Clarksville
country: United States
facility: DS Research
state: Indiana
city: Overland Park
country: United States
facility: Epiphany Dermatology of Kansas, LLC
state: Kansas
city: Louisville
country: United States
facility: Skin Sciences Pllc
state: Kentucky
city: Louisville
country: United States
facility: Scott Health Services LLC
state: Kentucky
city: Clarkston
country: United States
facility: Clarkston Skin Research
state: Michigan
city: Henderson
country: United States
facility: J Woodson Dermatology and Associates
state: Nevada
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: Stony Brook
country: United States
facility: DermResearch Center of New York Inc
state: New York
city: Nashville
country: United States
facility: Tennessee Clinical Research Center
state: Tennessee
city: Dallas
country: United States
facility: Modern Research Associates
state: Texas
city: Spokane
country: United States
facility: Premier Clinical Research
state: Washington
city: Sydney
country: Australia
facility: Holdsworth House Medical Practice
state: New South Wales
city: Woolloongabba
country: Australia
facility: Veracity Clinical Research
state: Queensland
city: Carlton
country: Australia
facility: Skin Health Institute
state: Victoria
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
city: Fremantle
country: Australia
facility: Fremantle Dermatology
state: Western Australia
city: Surrey
country: Canada
facility: Doctor Chih-Ho Hong Medical Incorporated
state: British Columbia
city: London
country: Canada
facility: DermEffects
state: Ontario
city: Markham
country: Canada
facility: Lynderm Research Inc
state: Ontario
city: Mississauga
country: Canada
facility: Cheema Research Incorporated
state: Ontario
city: Newmarket
country: Canada
facility: SKDS Research Incorporated
state: Ontario
city: North York
country: Canada
facility: Gordon Sussman Clinical Research Incorporated
state: Ontario
city: Ottawa
country: Canada
facility: JRB Research Incorporated
state: Ontario
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv Anny v Brne
city: Novy Jicin
country: Czechia
facility: Nemocnice Novy Jicin as
city: Ostrava-Poruba
country: Czechia
facility: Fakultni nemocnice Ostrava
city: Praha 1
country: Czechia
facility: Sanatorium profesora Arenbergera
city: Praha 8
country: Czechia
facility: Nemocnice Na Bulovce
city: Tallinn
country: Estonia
facility: North Estonia Medical Centre
city: Tartu
country: Estonia
facility: Clinical Research Centre
city: Tartu
country: Estonia
facility: Tartu University Hospital
city: Berlin
country: Germany
facility: CharitÃ© Berlin
city: GÃ¶ttingen
country: Germany
facility: UniversitÃ¤tsmedizin GÃ¶ttingen - Georg-August-UniversitÃ¤t
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Budapest
country: Hungary
facility: Csalogany Orvosi Kozpont
city: Budapest
country: Hungary
facility: Obudai Egeszsegugyi Centrum Kft
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Kenezy Gyula Egyetemi Korhaz
city: Miskolc
country: Hungary
facility: CRU Hungary Kft
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem Klinikai Kozpont
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont Altalanos Orvostudomanyi Kar
city: Sakura-shi
country: Japan
facility: Toho University Sakura Medical Center
state: Chiba
city: Fukuoka-shi
country: Japan
facility: Fukuoka University Hospital
state: Fukuoka
city: Obihiro-shi
country: Japan
facility: Takagi Dermatological Clinic
state: Hokkaido
city: Sapporo-shi
country: Japan
facility: Medical Corporation Kojinkai Sapporo Skin Clinic
state: Hokkaido
city: Nishinomiya-shi
country: Japan
facility: Meiwa Hospital
state: Hyogo
city: Nagasaki-shi
country: Japan
facility: Nagasaki University Hospital
state: Nagasaki
city: Sakai-shi
country: Japan
facility: Kume Clinic
state: Osaka
city: Bunkyo-ku
country: Japan
facility: Nippon Medical School Hospital
state: Tokyo
city: Chiyoda-ku
country: Japan
facility: Japan Post Holdings Co Ltd Tokyo Teishin Hospital
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: NTT Medical Center Tokyo
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Center Hospital of the National Center for Global Health and Medicine
state: Tokyo
city: Takaoka-shi
country: Japan
facility: Shirasaki Dermatology Clinic
state: Toyama
city: Seoul
country: Korea, Republic of
facility: Hallym University Kangnam Sacred Heart Hospital
city: Riga
country: Latvia
facility: Riga First Hospital
city: Riga
country: Latvia
facility: J Kisis
city: Riga
country: Latvia
facility: Clinic Latvian Dermatology Institute
city: Ventspils
country: Latvia
facility: Outpatient Clinic of Ventspils
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Lodz
country: Poland
facility: Centrum Terapii Wspolczesnej J M Jasnorzewska Spolka Komandytowo-Akcyjna
city: Lodz
country: Poland
facility: Dermoklinika Centrum Medyczne Spolka cywilna M Kierstan J Narbutt A Lesiak
city: Lublin
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej Med Laser Borzecki Spolka Jawna
city: Swidnik
country: Poland
facility: Tomasz Blicharski Lubelskie Centrum Diagnostyczne
city: Warszawa
country: Poland
facility: Centrum Medyczne Pratia Warszawa
city: Wroclaw
country: Poland
facility: Medicus Sp z o o
city: Wroclaw
country: Poland
facility: DermMedica Spzoo
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
state: AndalucÃ-a
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
state: CataluÃ±a
city: Barcelona
country: Spain
facility: Hospital del Mar
state: CataluÃ±a
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
state: CataluÃ±a
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
state: Comunidad Valenciana
city: Madrid
country: Spain
facility: Hospital Universitario de La Princesa
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Chernivtsi
country: Ukraine
facility: Chernivtsi Regional Skin and Venereal Dispensary
city: Dnipro
country: Ukraine
facility: Regional Skin and Venereal Dispensary
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk Regional Skin and Venereal Dispensary
city: Kyiv
country: Ukraine
facility: Medical clinic Blagomed
city: Uzhhorod
country: Ukraine
facility: Asclepius
city: Zaporizhzhia
country: Ukraine
facility: Military Hospital, Military Unit A3309 of the Military Medical Clinical Center
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
city: London
country: United Kingdom
facility: Whipps Cross University Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: