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

Atopic Dermatitis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03809663
• Other study ID #: 20170755
• Secondary ID: 2018-001997-52
• Status: Terminated
• Phase: Phase 2
• Start date: March 15, 2019
• Est. completion date: December 22, 2020

Study information

• Verified date: March 2022
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Terminated
• Enrollment: 251
• Est. completion date: December 22, 2020
• Est. primary completion date: May 12, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

Drug:
• Tezepelumab
Solution for injection

Other:
• Placebo
Placebo solution for injection

Locations

Country	Name	City	State
Australia	Skin Health Institute	Carlton	Victoria
Australia	Fremantle Dermatology	Fremantle	Western Australia
Australia	The Royal Melbourne Hospital	Parkville	Victoria
Australia	Holdsworth House Medical Practice	Sydney	New South Wales
Australia	Veracity Clinical Research	Woolloongabba	Queensland
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	Doctor Chih-Ho Hong Medical Incorporated	Surrey	British Columbia
Czechia	Fakultni nemocnice u sv Anny v Brne	Brno
Czechia	Nemocnice Novy Jicin as	Novy Jicin
Czechia	Fakultni nemocnice Ostrava	Ostrava-Poruba
Czechia	Sanatorium profesora Arenbergera	Praha 1
Czechia	Nemocnice Na Bulovce	Praha 8
Estonia	North Estonia Medical Centre	Tallinn
Estonia	Clinical Research Centre	Tartu
Estonia	Tartu University Hospital	Tartu
Germany	Charité Berlin	Berlin
Germany	Universitätsmedizin Göttingen - Georg-August-Universität	Göttingen
Germany	Medizinische Hochschule Hannover	Hannover
Hungary	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	Pecs
Hungary	Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont Altalanos Orvostudomanyi Kar	Szeged
Japan	Nippon Medical School Hospital	Bunkyo-ku	Tokyo
Japan	Japan Post Holdings Co Ltd Tokyo Teishin Hospital	Chiyoda-ku	Tokyo
Japan	Fukuoka University Hospital	Fukuoka-shi	Fukuoka
Japan	Nagasaki University Hospital	Nagasaki-shi	Nagasaki
Japan	Meiwa Hospital	Nishinomiya-shi	Hyogo
Japan	Takagi Dermatological Clinic	Obihiro-shi	Hokkaido
Japan	Kume Clinic	Sakai-shi	Osaka
Japan	Toho University Sakura Medical Center	Sakura-shi	Chiba
Japan	Medical Corporation Kojinkai Sapporo Skin Clinic	Sapporo-shi	Hokkaido
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
Korea, Republic of	Hallym University Kangnam Sacred Heart Hospital	Seoul
Latvia	Clinic Latvian Dermatology Institute	Riga
Latvia	J Kisis	Riga
Latvia	Riga First Hospital	Riga
Latvia	Outpatient Clinic of Ventspils	Ventspils
Poland	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	Swidnik
Poland	Centrum Medyczne Pratia Warszawa	Warszawa
Poland	DermMedica Spzoo	Wroclaw
Poland	Medicus Sp z o o	Wroclaw
Spain	Hospital General Universitario de Alicante	Alicante	Comunidad Valenciana
Spain	Hospital Universitari Germans Trias i Pujol	Badalona	Cataluña
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona	Cataluña
Spain	Hospital del Mar	Barcelona	Cataluña
Spain	Hospital Universitario de La Princesa	Madrid
Spain	Hospital Universitario Virgen Macarena	Sevilla	AndalucÃ-a
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
Ukraine	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
United Kingdom	Ninewells Hospital	Dundee
United Kingdom	Whipps Cross University Hospital	London
United Kingdom	Southampton General Hospital	Southampton
United States	Hamilton Research, LLC	Alpharetta	Georgia
United States	Clarkston Skin Research	Clarkston	Michigan
United States	DS Research	Clarksville	Indiana
United States	Modern Research Associates	Dallas	Texas
United States	First OC Dermatology	Fountain Valley	California
United States	J Woodson Dermatology and Associates	Henderson	Nevada
United States	Scott Health Services LLC	Louisville	Kentucky
United States	Skin Sciences Pllc	Louisville	Kentucky
United States	Tennessee Clinical Research Center	Nashville	Tennessee
United States	Mount Sinai Hospital	New York	New York
United States	Epiphany Dermatology of Kansas, LLC	Overland Park	Kansas
United States	Clinical Science Institute	Santa Monica	California
United States	Premier Clinical Research	Spokane	Washington
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	DermResearch Center of New York Inc	Stony Brook	New York
United States	Dundee Dermatology	West Dundee	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Amgen	AstraZeneca

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Czechia,  Estonia,  Germany,  Hungary,  Japan,  Korea, Republic of,  Latvia,  Poland,  Spain,  Switzerland,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Number of Participants Who Experienced a 50% or 90% Reduction From Baseline in Eczema Area and Severity Index (EASI 50/90) 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	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)
Secondary	Change From Baseline in Scoring of Atopic Dermatitis (SCORAD) at 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.	Baseline and Week 16
Secondary	Change From Baseline in Pruritus Numeric Rating Scale (NRS) at 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.	Baseline and Week 16
Secondary	Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration	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.	Pre-dose on Day 1, Week 2, 4, 12, 16, 24, 32, 40, 48, 50, 52, 58 and 70
Secondary	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

External Links

•   AmgenTrials clinical trials website