A Dose Ranging Placebo-Controlled Double-Blind Study to Evaluate the Safety and Efficacy of Tezepelumab in Atopic Dermatitis
- Registration Number
- NCT03809663
- Lead Sponsor
- Amgen
- 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).
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 251
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Subject has provided informed consent prior to initiation of any study specific activities/procedures.
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Age greater than or equal to 18 to less than or equal to 75 years at screening.
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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).
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AD that affects greater than or equal to' 10% body surface area as assessed by EASI at screening and on day 1.
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An IGA score of greater than or equal to 3 at screening and on day 1.
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An EASI score of greater than or equal to 16 at screening and on day 1.
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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
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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).
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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.
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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.
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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.
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Documented medical history of chronic alcohol or drug abuse within 12 months prior to screening.
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History of anaphylaxis following any biologic therapy.
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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).
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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
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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.
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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.
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Other Medical Conditions>
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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.
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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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A: Tezepelumab 280 mg Tezepelumab 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. Part A: Placebo 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. Part B: Placebo and Topical Corticosteroids Regimen Tezepelumab Matching placebo administered via SC injection Q2W with topical corticosteroids (TCS) for a maximum of 52 weeks. Part A: Tezepelumab 210 mg Tezepelumab 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. Part A: Tezepelumab 420 mg Tezepelumab Tezepelumab 420 mg administered via SC injection Q2W for a maximum of 52 weeks. Part B: Tezepelumab 420 mg and Topical Corticosteroids Regimen Tezepelumab Tezepelumab 420 mg administered via SC injection Q2W with TCS for a maximum of 52 weeks.
- Primary Outcome Measures
Name Time Method Number of Participants With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) (IGA 0/1) at Week 16 Week 16 The IGA allows investigators to assess overall disease severity at 1 given time point and consists of a 6-point severity scale from clear to severe disease
* 0 = clear
* 1 = almost clear
* 2 = mild disease
* 3 = moderate disease
* 4 = severe disease
* 5 = very severe disease
The IGA uses clinical characteristics of erythema, infiltration, papulation, oozing, and crusting as guidelines for the overall severity assessment (Breuer et al, 2004).
Participants who took rescue medication between Day 29 to Week 16 were considered non-responders.Number of Participants Who Experienced a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI 75) at Week 16 Baseline and Week 16 The EASI evaluates 4 natural anatomical regions for severity and extent of key disease signs and focuses on key acute and chronic signs of inflammation (ie, erythema, induration/papulation, excoriation, and lichenification).
A reduction in the EASI score indicates an improvement in severity. Participants who took rescue medication between Day 29 to Week 16 were considered non-responders.
- Secondary Outcome Measures
Name Time Method Number of Participants Who Experienced a 50% or 90% Reduction From Baseline in Eczema Area and Severity Index (EASI 50/90) at Week 16 Baseline and Week 16 The EASI evaluates 4 natural anatomical regions for severity and extent of key disease signs and focuses on key acute and chronic signs of inflammation (ie, erythema, induration/papulation, excoriation, and lichenification).
A reduction in the EASI score indicates an improvement in severity. Participants who took rescue medication between Day 29 to Week 16 were considered non-responders.Time to Achievement of 50%, 75% or 90% Reduction From Day 1 in Eczema Area and Severity Index (EASI 50/75/90) Day 1 up to End of Study Visit (Week 70) Change From Baseline in Scoring of Atopic Dermatitis (SCORAD) at Week 16 Baseline and Week 16 The SCORAD is a clinical tool for assessing the severity (ie, extent, intensity) of atopic dermatitis (AD). The tool evaluates the extent and intensity of the AD lesions, along with subjective symptoms (Kunz et al, 1997). The total score ranges from 0 to 103, with higher values indicating more severe disease. A negative change from baseline indicates an improvement in severity of disease.
Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 16 Baseline and Week 16 Pruritus was assessed using an NRS (0-10) with 0 = no itch and 10 = worst imaginable itch. A negative change from baseline indicates an improvement in symptoms.
Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration Pre-dose on Day 1, Week 2, 4, 12, 16, 24, 32, 40, 48, 50, 52, 58 and 70 Switchers were included up to Week 16 and were then excluded from the analysis after switching. All Tezepelumab participants received 420 mg of Tezepelumab on Day 1.
Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16 Pre-dose on Week 24, 32, 40, 48, 50, 52, 58 and 70
Trial Locations
- Locations (86)
Clinical Science Institute
🇺🇸Santa Monica, California, United States
J Woodson Dermatology and Associates
🇺🇸Henderson, Nevada, United States
CRU Hungary Kft
🇭🇺Miskolc, Hungary
Outpatient Clinic of Ventspils
🇱🇻Ventspils, Latvia
Tartu University Hospital
🇪🇪Tartu, Estonia
Clinic Latvian Dermatology Institute
🇱🇻Riga, Latvia
Asclepius
🇺🇦Uzhhorod, Ukraine
Lynderm Research Inc
🇨🇦Markham, Ontario, Canada
Cheema Research Incorporated
🇨🇦Mississauga, Ontario, Canada
SKDS Research Incorporated
🇨🇦Newmarket, Ontario, Canada
Takagi Dermatological Clinic
🇯🇵Obihiro-shi, Hokkaido, Japan
Holdsworth House Medical Practice
🇦🇺Sydney, New South Wales, Australia
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States
Modern Research Associates
🇺🇸Dallas, Texas, United States
Skin Sciences Pllc
🇺🇸Louisville, Kentucky, United States
Clarkston Skin Research
🇺🇸Clarkston, Michigan, United States
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
North Estonia Medical Centre
🇪🇪Tallinn, Estonia
Fremantle Dermatology
🇦🇺Fremantle, Western Australia, Australia
Charité Berlin
🇩🇪Berlin, Germany
Nemocnice Novy Jicin as
🇨🇿Novy Jicin, Czechia
Fakultni nemocnice Ostrava
🇨🇿Ostrava-Poruba, Czechia
Skin Health Institute
🇦🇺Carlton, Victoria, Australia
Riga First Hospital
🇱🇻Riga, Latvia
Csalogany Orvosi Kozpont
🇭🇺Budapest, Hungary
Medical Corporation Kojinkai Sapporo Skin Clinic
🇯🇵Sapporo-shi, Hokkaido, Japan
Universitätsmedizin Göttingen - Georg-August-Universität
🇩🇪Göttingen, Germany
Ivano-Frankivsk Regional Skin and Venereal Dispensary
🇺🇦Ivano-Frankivsk, Ukraine
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, AndalucÃ-a, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Cataluña, Spain
First OC Dermatology
🇺🇸Fountain Valley, California, United States
Hamilton Research, LLC
🇺🇸Alpharetta, Georgia, United States
DS Research
🇺🇸Clarksville, Indiana, United States
Epiphany Dermatology of Kansas, LLC
🇺🇸Overland Park, Kansas, United States
Scott Health Services LLC
🇺🇸Louisville, Kentucky, United States
Mount Sinai Hospital
🇺🇸New York, New York, United States
DermResearch Center of New York Inc
🇺🇸Stony Brook, New York, United States
Premier Clinical Research
🇺🇸Spokane, Washington, United States
Veracity Clinical Research
🇦🇺Woolloongabba, Queensland, Australia
The Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
Doctor Chih-Ho Hong Medical Incorporated
🇨🇦Surrey, British Columbia, Canada
JRB Research Incorporated
🇨🇦Ottawa, Ontario, Canada
Fakultni nemocnice u sv Anny v Brne
🇨🇿Brno, Czechia
Gordon Sussman Clinical Research Incorporated
🇨🇦North York, Ontario, Canada
Nemocnice Na Bulovce
🇨🇿Praha 8, Czechia
Sanatorium profesora Arenbergera
🇨🇿Praha 1, Czechia
Clinical Research Centre
🇪🇪Tartu, Estonia
Obudai Egeszsegugyi Centrum Kft
🇭🇺Budapest, Hungary
Pecsi Tudomanyegyetem Klinikai Kozpont
🇭🇺Pecs, Hungary
Toho University Sakura Medical Center
🇯🇵Sakura-shi, Chiba, Japan
Meiwa Hospital
🇯🇵Nishinomiya-shi, Hyogo, Japan
Fukuoka University Hospital
🇯🇵Fukuoka-shi, Fukuoka, Japan
Nagasaki University Hospital
🇯🇵Nagasaki-shi, Nagasaki, Japan
Kume Clinic
🇯🇵Sakai-shi, Osaka, Japan
Nippon Medical School Hospital
🇯🇵Bunkyo-ku, Tokyo, Japan
Japan Post Holdings Co Ltd Tokyo Teishin Hospital
🇯🇵Chiyoda-ku, Tokyo, Japan
NTT Medical Center Tokyo
🇯🇵Shinagawa-ku, Tokyo, Japan
Center Hospital of the National Center for Global Health and Medicine
🇯🇵Shinjuku-ku, Tokyo, Japan
Hallym University Kangnam Sacred Heart Hospital
🇰🇷Seoul, Korea, Republic of
Shirasaki Dermatology Clinic
🇯🇵Takaoka-shi, Toyama, Japan
J Kisis
🇱🇻Riga, Latvia
Hospital del Mar
🇪🇸Barcelona, Cataluña, Spain
Tomasz Blicharski Lubelskie Centrum Diagnostyczne
🇵🇱Swidnik, Poland
Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Cataluña, Spain
Hospital Universitario de La Princesa
🇪🇸Madrid, Spain
Chernivtsi Regional Skin and Venereal Dispensary
🇺🇦Chernivtsi, Ukraine
Centre Hospitalier Universitaire Vaudois
🇨🇭Lausanne, Switzerland
Ninewells Hospital
🇬🇧Dundee, United Kingdom
Medical clinic Blagomed
🇺🇦Kyiv, Ukraine
Southampton General Hospital
🇬🇧Southampton, United Kingdom
Whipps Cross University Hospital
🇬🇧London, United Kingdom
Hospital General Universitario de Alicante
🇪🇸Alicante, Comunidad Valenciana, Spain
Debreceni Egyetem Kenezy Gyula Egyetemi Korhaz
🇭🇺Debrecen, Hungary
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont Altalanos Orvostudomanyi Kar
🇭🇺Szeged, Hungary
Medicus Sp z o o
🇵🇱Wroclaw, Poland
Niepubliczny Zaklad Opieki Zdrowotnej Med Laser Borzecki Spolka Jawna
🇵🇱Lublin, Poland
Centrum Medyczne Pratia Warszawa
🇵🇱Warszawa, Poland
Regional Skin and Venereal Dispensary
🇺🇦Dnipro, Ukraine
Military Hospital, Military Unit A3309 of the Military Medical Clinical Center
🇺🇦Zaporizhzhia, Ukraine
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Centrum Terapii Wspolczesnej J M Jasnorzewska Spolka Komandytowo-Akcyjna
🇵🇱Lodz, Poland
Dermoklinika Centrum Medyczne Spolka cywilna M Kierstan J Narbutt A Lesiak
🇵🇱Lodz, Poland
DermMedica Spzoo
🇵🇱Wroclaw, Poland
Dundee Dermatology
🇺🇸West Dundee, Illinois, United States
Tennessee Clinical Research Center
🇺🇸Nashville, Tennessee, United States
DermEffects
🇨🇦London, Ontario, Canada