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

NCT03809663 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 201707552018-001997-52
• Study Type: interventional
• Target: 251
• Locations: 14 countries
• Sites: 83

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).

Conditions

Atopic Dermatitis

Keywords

Atopic Dermatitis; eczema; tezepelumab; dermatology; dermatitis; inflammation; skin; moderate dermatitis; severe dermatitis

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) (IGA 0/1) at 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.

  Week 16

• Number of Participants Who Experienced a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI 75) at 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.

  Baseline and Week 16

Secondary Outcomes (6)

• 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

• 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

• Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 16

  Baseline and Week 16

• 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

Study Arms (6)

Part A: Placebo

PLACEBO COMPARATOR

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.

Other: Placebo

Part A: Tezepelumab 210 mg

EXPERIMENTAL

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.

Drug: Tezepelumab

Part A: Tezepelumab 280 mg

EXPERIMENTAL

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.

Drug: Tezepelumab

Part A: Tezepelumab 420 mg

EXPERIMENTAL

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

Drug: Tezepelumab

Part B: Placebo and Topical Corticosteroids Regimen

EXPERIMENTAL

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

Drug: Tezepelumab

Part B: Tezepelumab 420 mg and Topical Corticosteroids Regimen

EXPERIMENTAL

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

Drug: Tezepelumab

Interventions

Tezepelumab DRUG

Solution for injection

Also known as: AMG157

Part A: Tezepelumab 210 mg; Part A: Tezepelumab 280 mg; Part A: Tezepelumab 420 mg; Part B: Placebo and Topical Corticosteroids Regimen; Part B: Tezepelumab 420 mg and Topical Corticosteroids Regimen

Placebo OTHER

Placebo solution for injection

Part A: Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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:

Sponsors & Collaborators

• Amgen: lead
• AstraZeneca: collaborator

Study Sites (86)

First OC Dermatology

Fountain Valley, California, 92708, United States

Location

Clinical Science Institute

Santa Monica, California, 90404, United States

Location

Hamilton Research, LLC

Alpharetta, Georgia, 30022, United States

Location

Southern Illinois University School of Medicine

Springfield, Illinois, 62702, United States

Location

Dundee Dermatology

West Dundee, Illinois, 60118, United States

Location

DS Research

Clarksville, Indiana, 47129, United States

Location

Epiphany Dermatology of Kansas, LLC

Overland Park, Kansas, 66215, United States

Location

Skin Sciences Pllc

Louisville, Kentucky, 40217, United States

Location

Scott Health Services LLC

Louisville, Kentucky, 40241, United States

Location

Clarkston Skin Research

Clarkston, Michigan, 48346, United States

Location

J Woodson Dermatology and Associates

Henderson, Nevada, 89052, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

DermResearch Center of New York Inc

Stony Brook, New York, 11790, United States

Location

Tennessee Clinical Research Center

Nashville, Tennessee, 37215, United States

Location

Modern Research Associates

Dallas, Texas, 75231, United States

Location

Premier Clinical Research

Spokane, Washington, 99202, United States

Location

Holdsworth House Medical Practice

Sydney, New South Wales, 2010, Australia

Location

Veracity Clinical Research

Woolloongabba, Queensland, 4102, Australia

Location

Skin Health Institute

Carlton, Victoria, 3053, Australia

Location

The Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Fremantle Dermatology

Fremantle, Western Australia, 6160, Australia

Location

Doctor Chih-Ho Hong Medical Incorporated

Surrey, British Columbia, V3R 6A7, Canada

Location

DermEffects

London, Ontario, N6H 5L5, Canada

Location

Lynderm Research Inc

Markham, Ontario, L3P 1X3, Canada

Location

Cheema Research Incorporated

Mississauga, Ontario, L5A 3V4, Canada

Location

SKDS Research Incorporated

Newmarket, Ontario, L3Y 5G8, Canada

Location

Gordon Sussman Clinical Research Incorporated

North York, Ontario, M3B 3S6, Canada

Location

JRB Research Incorporated

Ottawa, Ontario, K1H 7X3, Canada

Location

Fakultni nemocnice u sv Anny v Brne

Brno, 656 91, Czechia

Location

Nemocnice Novy Jicin as

Nový Jičín, 741 01, Czechia

Location

Fakultni nemocnice Ostrava

Ostrava-Poruba, 708 52, Czechia

Location

Sanatorium profesora Arenbergera

Prague, 110 00, Czechia

Location

Nemocnice Na Bulovce

Prague, 180 81, Czechia

Location

North Estonia Medical Centre

Tallinn, 13419, Estonia

Location

Clinical Research Centre

Tartu, 50106, Estonia

Location

Tartu University Hospital

Tartu, 50417, Estonia

Location

Charité Berlin

Berlin, 10117, Germany

Location

Universitätsmedizin Göttingen - Georg-August-Universität

Göttingen, 37075, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Csalogany Orvosi Kozpont

Budapest, 1027, Hungary

Location

Obudai Egeszsegugyi Centrum Kft

Budapest, 1036, Hungary

Location

Debreceni Egyetem Kenezy Gyula Egyetemi Korhaz

Debrecen, 4031, Hungary

Location

CRU Hungary Kft

Miskolc, 3529, Hungary

Location

Pecsi Tudomanyegyetem Klinikai Kozpont

Pécs, 7632, Hungary

Location

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont Altalanos Orvostudomanyi Kar

Szeged, 6720, Hungary

Location

Toho University Sakura Medical Center

Sakura-shi, Chiba, 285-8741, Japan

Location

Fukuoka University Hospital

Fukuoka, Fukuoka, 814-0180, Japan

Location

Takagi Dermatological Clinic

Obihiro-shi, Hokkaido, 080-0013, Japan

Location

Medical Corporation Kojinkai Sapporo Skin Clinic

Sapporo, Hokkaido, 060-0063, Japan

Location

Meiwa Hospital

Nishinomiya-shi, Hyōgo, 663-8186, Japan

Location

Nagasaki University Hospital

Nagasaki, Nagasaki, 852-8501, Japan

Location

Kume Clinic

Sakai-shi, Osaka, 593-8324, Japan

Location

Nippon Medical School Hospital

Bunkyo-ku, Tokyo, 113-8603, Japan

Location

Japan Post Holdings Co Ltd Tokyo Teishin Hospital

Chiyoda-ku, Tokyo, 102-8798, Japan

Location

NTT Medical Center Tokyo

Shinagawa-ku, Tokyo, 141-8625, Japan

Location

Center Hospital of the National Center for Global Health and Medicine

Shinjuku-ku, Tokyo, 162-8655, Japan

Location

Shirasaki Dermatology Clinic

Takaoka-shi, Toyama, 933-0871, Japan

Location

Riga First Hospital

Riga, 1001, Latvia

Location

J Kisis

Riga, 1003, Latvia

Location

Clinic Latvian Dermatology Institute

Riga, 1011, Latvia

Location

Outpatient Clinic of Ventspils

Ventspils, 3601, Latvia

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-214, Poland

Location

Centrum Terapii Wspolczesnej J M Jasnorzewska Spolka Komandytowo-Akcyjna

Lodz, 90-242, Poland

Location

Dermoklinika Centrum Medyczne Spolka cywilna M Kierstan J Narbutt A Lesiak

Lodz, 90-436, Poland

Location

Niepubliczny Zaklad Opieki Zdrowotnej Med Laser Borzecki Spolka Jawna

Lublin, 20-406, Poland

Location

Tomasz Blicharski Lubelskie Centrum Diagnostyczne

Świdnik, 21-040, Poland

Location

Centrum Medyczne Pratia Warszawa

Warsaw, 01-868, Poland

Location

Medicus Sp z o o

Wroclaw, 50-224, Poland

Location

DermMedica Spzoo

Wroclaw, 51-318, Poland

Location

Hallym University Kangnam Sacred Heart Hospital

Seoul, 07441, South Korea

Location

Hospital Universitario Virgen Macarena

Seville, AndalucÃ-a, 41009, Spain

Location

Hospital Universitari Germans Trias i Pujol

Badalona, Cataluña, 08916, Spain

Location

Hospital del Mar

Barcelona, Cataluña, 08003, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Cataluña, 08041, Spain

Location

Hospital General Universitario de Alicante

Alicante, Valencia, 03010, Spain

Location

Hospital Universitario de La Princesa

Madrid, 28006, Spain

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, 1011, Switzerland

Location

Chernivtsi Regional Skin and Venereal Dispensary

Chernivtsi, 58002, Ukraine

Location

Regional Skin and Venereal Dispensary

Dnipro, 49074, Ukraine

Location

Ivano-Frankivsk Regional Skin and Venereal Dispensary

Ivano-Frankivsk, 76018, Ukraine

Location

Medical clinic Blagomed

Kyiv, 02000, Ukraine

Location

Asclepius

Uzhhorod, 88000, Ukraine

Location

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

Zaporizhzhia, 69000, Ukraine

Location

Ninewells Hospital

Dundee, DD1 9SY, United Kingdom

Location

Whipps Cross University Hospital

London, E11 1NR, United Kingdom

Location

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Dermatitis, Atopic; Eczema; Dermatitis; Inflammation

Interventions

tezepelumab

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Enrollment of Part A of this study was completed as of 27 July 2020. The study was terminated prior to the enrollment of any participants into Part B.

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: January 10, 2019
• First Posted: January 18, 2019
• Study Start: March 15, 2019
• Primary Completion: May 12, 2020
• Study Completion: December 22, 2020
• Last Updated: March 10, 2022
• Results First Posted: March 10, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: 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.
• Access Criteria: 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.

Locations

UA (6); DE (3); CA (7); CZ (5); US (16); ES (6); CH (1); JP (12); HU (6); AU (5); LA (4); GB (3); PL (8); KR (1)