A Dose Ranging Placebo-Controlled Double-Blind Study to Evaluate the Safety and Efficacy of Tezepelumab in Atopic Dermatitis

NCT ID: NCT03809663

Last Updated: 2022-03-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 251 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-15
• Study Completion Date: 2020-12-22

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).

Conditions

Atopic Dermatitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo solution for injection

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.

Group Type: EXPERIMENTAL

Tezepelumab

Intervention Type: DRUG

Solution for injection

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.

Group Type: EXPERIMENTAL

Tezepelumab

Intervention Type: DRUG

Solution for injection

Part A: Tezepelumab 420 mg

Tezepelumab 420 mg administered via SC injection Q2W for a maximum of 52 weeks.

Group Type: EXPERIMENTAL

Tezepelumab

Intervention Type: DRUG

Solution for injection

Part B: Placebo and Topical Corticosteroids Regimen

Matching placebo administered via SC injection Q2W with topical corticosteroids (TCS) for a maximum of 52 weeks.

Group Type: EXPERIMENTAL

Tezepelumab

Intervention Type: DRUG

Solution for injection

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.

Group Type: EXPERIMENTAL

Tezepelumab

Intervention Type: DRUG

Solution for injection

Interventions

Tezepelumab

Solution for injection

Intervention Type: DRUG

Placebo

Placebo solution for injection

Intervention Type: OTHER

Other Intervention Names

AMG157

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

First OC Dermatology

Fountain Valley, California, United States

Clinical Science Institute

Santa Monica, California, United States

Hamilton Research, LLC

Alpharetta, Georgia, United States

Southern Illinois University School of Medicine

Springfield, Illinois, United States

Dundee Dermatology

West Dundee, Illinois, United States

DS Research

Clarksville, Indiana, United States

Epiphany Dermatology of Kansas, LLC

Overland Park, Kansas, United States

Skin Sciences Pllc

Louisville, Kentucky, United States

Scott Health Services LLC

Louisville, Kentucky, United States

Clarkston Skin Research

Clarkston, Michigan, United States

J Woodson Dermatology and Associates

Henderson, Nevada, United States

Mount Sinai Hospital

New York, New York, United States

DermResearch Center of New York Inc

Stony Brook, New York, United States

Tennessee Clinical Research Center

Nashville, Tennessee, United States

Modern Research Associates

Dallas, Texas, United States

Premier Clinical Research

Spokane, Washington, United States

Holdsworth House Medical Practice

Sydney, New South Wales, Australia

Veracity Clinical Research

Woolloongabba, Queensland, Australia

Skin Health Institute

Carlton, Victoria, Australia

The Royal Melbourne Hospital

Parkville, Victoria, Australia

Fremantle Dermatology

Fremantle, Western Australia, Australia

Doctor Chih-Ho Hong Medical Incorporated

Surrey, British Columbia, Canada

DermEffects

London, Ontario, Canada

Lynderm Research Inc

Markham, Ontario, Canada

Cheema Research Incorporated

Mississauga, Ontario, Canada

SKDS Research Incorporated

Newmarket, Ontario, Canada

Gordon Sussman Clinical Research Incorporated

North York, Ontario, Canada

JRB Research Incorporated

Ottawa, Ontario, Canada

Fakultni nemocnice u sv Anny v Brne

Brno, , Czechia

Nemocnice Novy Jicin as

Nový Jičín, , Czechia

Fakultni nemocnice Ostrava

Ostrava-Poruba, , Czechia

Sanatorium profesora Arenbergera

Prague, , Czechia

Nemocnice Na Bulovce

Prague, , Czechia

North Estonia Medical Centre

Tallinn, , Estonia

Clinical Research Centre

Tartu, , Estonia

Tartu University Hospital

Tartu, , Estonia

Charité Berlin

Berlin, , Germany

Universitätsmedizin Göttingen - Georg-August-Universität

Göttingen, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Csalogany Orvosi Kozpont

Budapest, , Hungary

Obudai Egeszsegugyi Centrum Kft

Budapest, , Hungary

Debreceni Egyetem Kenezy Gyula Egyetemi Korhaz

Debrecen, , Hungary

CRU Hungary Kft

Miskolc, , Hungary

Pecsi Tudomanyegyetem Klinikai Kozpont

Pécs, , Hungary

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont Altalanos Orvostudomanyi Kar

Szeged, , Hungary

Toho University Sakura Medical Center

Sakura-shi, Chiba, Japan

Fukuoka University Hospital

Fukuoka, Fukuoka, Japan

Takagi Dermatological Clinic

Obihiro-shi, Hokkaido, Japan

Medical Corporation Kojinkai Sapporo Skin Clinic

Sapporo, Hokkaido, Japan

Meiwa Hospital

Nishinomiya-shi, Hyōgo, Japan

Nagasaki University Hospital

Nagasaki, 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

Shirasaki Dermatology Clinic

Takaoka-shi, Toyama, Japan

Riga First Hospital

Riga, , Latvia

J Kisis

Riga, , Latvia

Clinic Latvian Dermatology Institute

Riga, , Latvia

Outpatient Clinic of Ventspils

Ventspils, , Latvia

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

Niepubliczny Zaklad Opieki Zdrowotnej Med Laser Borzecki Spolka Jawna

Lublin, , Poland

Tomasz Blicharski Lubelskie Centrum Diagnostyczne

Świdnik, , Poland

Centrum Medyczne Pratia Warszawa

Warsaw, , Poland

Medicus Sp z o o

Wroclaw, , Poland

DermMedica Spzoo

Wroclaw, , Poland

Hallym University Kangnam Sacred Heart Hospital

Seoul, , South Korea

Hospital Universitario Virgen Macarena

Seville, AndalucÃ-a, Spain

Hospital Universitari Germans Trias i Pujol

Badalona, Cataluña, Spain

Hospital del Mar

Barcelona, Cataluña, Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, Cataluña, Spain

Hospital General Universitario de Alicante

Alicante, Valencia, Spain

Hospital Universitario de La Princesa

Madrid, , Spain

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Chernivtsi Regional Skin and Venereal Dispensary

Chernivtsi, , Ukraine

Regional Skin and Venereal Dispensary

Dnipro, , Ukraine

Ivano-Frankivsk Regional Skin and Venereal Dispensary

Ivano-Frankivsk, , Ukraine

Medical clinic Blagomed

Kyiv, , Ukraine

Asclepius

Uzhhorod, , Ukraine

Military Hospital, Military Unit A3309 of the Military Medical Clinical Center

Zaporizhzhia, , Ukraine

Ninewells Hospital

Dundee, , United Kingdom

Whipps Cross University Hospital

London, , United Kingdom

Southampton General Hospital

Southampton, , United Kingdom

Countries

United States; Australia; Canada; Czechia; Estonia; Germany; Hungary; Japan; Latvia; Poland; South Korea; Spain; Switzerland; Ukraine; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

2018-001997-52

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

20170755

Identifier Type: -

Identifier Source: org_study_id