Clinical trial NCT03575871: Study Evaluating Efficacy and Safety of PF-04965842 in Subjects Aged 12 Years And Older With Moderate to Severe Atopic Dermatitis
Official title: A PHASE 3 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP, MULTI-CENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF PF-04965842 MONOTHERAPY IN SUBJECTS AGED 12 YEARS AND OLDER, WITH MODERATE TO SEVERE ATOPIC DERMATITIS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Dermatitis, Atopic
Keywords: atopic dermatitis
atopic eczema
eczema
JAK
janus kinase
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2018-07-03
Enrollment: 391
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: B7451013 is a Phase 3 study to evaluate PF-04965842 in patients aged 12 years and older with a minimum body weight of 40 kg who have moderate to severe atopic dermatitis. The efficacy and safety of two dosage strengths of PF-04965842, 100 mg and 200 mg taken orally once daily, will be evaluated relative to placebo over 12 weeks of study participation. Eligible patients will have an option to enter a long-term extension study after completing 12 weeks of treatment.


Eligibility criteria: Inclusion Criteria:

* 12 years of age or older with a minimum body weight of 40 kg
* Diagnosis of atopic dermatitis (AD) for at least 1 year and current status of moderate to severe disease (\>= the following scores: BSA 10%, IGA 3, EASI 16, Pruritus NRS severity 4)
* Recent history of inadequate response or inability to tolerate topical AD treatments or require systemic treatments for AD control

Exclusion Criteria:

* Unwilling to discontinue current AD medications prior to the study or require treatment with prohibited medications during the study
* Prior treatment with JAK inhibitors
* Other active nonAD inflammatory skin diseases or conditions affecting skin
* Medical history including thrombocytopenia, coagulopathy or platelet dysfunction, Q wave interval abnormalities, current or history of certain infections, cancer, lymphoproliferative disorders and other medical conditions at the discretion of the investigator
* Pregnant or breastfeeding women, or women of childbearing potential who are unwilling to use contraception

Primary outcomes:
measure: Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of Clear (0) or Almost Clear (1) and Greater Than or Equal to (>=) 2 Points Improvement From Baseline at Week 12
timeFrame: Baseline, Week 12
measure: Percentage of Participants Achieving Eczema Area and Severity Index Response of >=75 Percent (%) Improvement (EASI-75) From Baseline at Week 12
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Percentage of Participants Who Achieved at Least 4-Points Improvement From Baseline in the Numerical Rating Scale (NRS) for Severity of Pruritus at Weeks 2, 4, 8 and 12
timeFrame: Baseline, Weeks 2, 4, 8 and 12
measure: Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) Total Score at Week 12
timeFrame: Baseline, Week 12
measure: Time to Achieve >=4 Points Improvement From Baseline in Numerical Rating Scale (NRS) for Severity of Pruritus
timeFrame: Baseline up to Day 15
measure: Percentage of Participants Achieving Eczema Area and Severity Index Response of >=75% Improvement (EASI-75) From Baseline at Weeks 2, 4 and 8
timeFrame: Baseline, Weeks 2, 4, and 8
measure: Percentage of Participants Achieving IGA Response of Clear (0) or Almost Clear (1) and >=2 Points Improvement From Baseline at Weeks 2, 4 and 8
timeFrame: Baseline, Weeks 2, 4, and 8
measure: Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of Clear (0) at Week 2, 4, 8 and 12
timeFrame: Weeks 2, 4, 8 and 12
measure: Percentage of Participants Achieving Eczema Area and Severity Index Response of >=50% Improvement (EASI-50) From Baseline at Weeks 2, 4, 8 and 12
timeFrame: Baseline, Weeks 2, 4, 8, and 12
measure: Percentage of Participants Achieving Eczema Area and Severity Index Response of >=90% Improvement (EASI-90) From Baseline at Weeks 2, 4, 8 and 12
timeFrame: Baseline, Weeks 2, 4, 8, and 12
measure: Percentage of Participants Achieving Eczema Area and Severity Index Response of 100% Improvement (EASI-100) From Baseline at Weeks 2, 4, 8 and 12
timeFrame: Baseline, Weeks 2, 4, 8, and 12
measure: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 2, 4, 8 and 12
timeFrame: Baseline, Weeks 2, 4, 8, and 12
measure: Change From Baseline in the Percentage Body Surface Area (%BSA) Affected at Week 2, 4, 8, and 12
timeFrame: Baseline, Weeks 2, 4, 8, and 12
measure: Percentage of Participants With Percentage Body Surface Area (%BSA) (From EASI) < 5% at Weeks 2, 4, 8 and 12
timeFrame: Weeks 2, 4, 8, and 12
measure: Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=50% Improvement From Baseline at Week 2, 4, 8 and 12
timeFrame: Baseline, Weeks 2, 4, 8, and 12
measure: Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=75% Improvement From Baseline at Week 2, 4, 8 and 12
timeFrame: Baseline, Weeks 2, 4, 8, and 12
measure: Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) of Itch at Weeks 2, 4, 8 and 12
timeFrame: Baseline, Weeks 2, 4, 8, and 12
measure: Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) Sleep Loss at Weeks 2, 4, 8 and 12
timeFrame: Baseline, Weeks 2, 4, 8, and 12
measure: Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Total Score at Week 2, 4, 8 and 12
timeFrame: Baseline, Weeks 2, 4, 8, and 12
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Emmaus Research Center, Inc.
state: California
city: Los Alamitos
country: United States
facility: Advanced Research Center, Inc. - Los Alamitos Site
state: California
city: Rolling Hills Estates
country: United States
facility: Peninsula Research Associates, Inc.
state: California
city: Santa Monica
country: United States
facility: Clinical Science Institute
state: California
city: Colorado Springs
country: United States
facility: Asthma and Allergy Associates, PC
state: Colorado
city: Colorado Springs
country: United States
facility: Colorado Springs Dermatology Clinic, PC
state: Colorado
city: Clearwater
country: United States
facility: Olympian Clinical Research
state: Florida
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Florida
city: Jacksonville
country: United States
facility: Precision Imaging
state: Florida
city: Jacksonville
country: United States
facility: Solutions Through Advanced Research, Inc.
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions, Inc
state: Florida
city: Tampa
country: United States
facility: ForCare Clinical Research
state: Florida
city: Caldwell
country: United States
facility: Imaging Center of Idaho
state: Idaho
city: Nampa
country: United States
facility: ASR, LLC
state: Idaho
city: Baton Rouge
country: United States
facility: Meridian Clinical Research
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Saint Joseph
country: United States
facility: MediSearch Clinical Trials
state: Missouri
city: New York
country: United States
facility: Sadick Research Group
state: New York
city: Wilmington
country: United States
facility: PMG Research of Wilmington, LLC
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Gahanna
country: United States
facility: The Ohio State University Dermatology East
state: Ohio
city: Memphis
country: United States
facility: Tanenbaum Dermatology Center
state: Tennessee
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Tennessee
city: Austin
country: United States
facility: Austin Institute for Clinical Research, Inc. - Central
state: Texas
city: Houston
country: United States
facility: Center for Clinical Studies, LTD. LLP
state: Texas
city: Houston
country: United States
facility: West Houston Dermatology, PA
state: Texas
city: Franklin
country: United States
facility: Summit Clinical Research, LLC
state: Virginia
city: Norfolk
country: United States
facility: Virginia Dermatology and Skin Cancer Center
state: Virginia
city: Maroubra
country: Australia
facility: Australian Clinical Research Network
state: New South Wales
city: Benowa
country: Australia
facility: The Skin Centre
state: Queensland
city: Woolloongabba
country: Australia
facility: Veracity Clinical Research Pty Ltd
state: Queensland
city: Carlton
country: Australia
facility: Skin and Cancer Foundation Inc
state: Victoria
city: East Melbourne
country: Australia
facility: Sinclair Dermatology
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Parkville
country: Australia
facility: The Royal Children's Hospital (RCH)
state: Victoria
city: Dupnitsa
country: Bulgaria
facility: Medical Centre Asklepii OOD
city: Gabrovo
country: Bulgaria
facility: MHAT Dr. Tota Venkova AD
city: Sofia
country: Bulgaria
facility: "Acibadem City Clinic MHAT Tokuda" EAD
city: Sofia
country: Bulgaria
facility: "DCC Aleksandrovska" EOOD
city: Sofia
country: Bulgaria
facility: Diagnostic Consultative Center Fokus-5
city: Sofia
country: Bulgaria
facility: Medical Centre Synexus Sofia EOOD
city: Vancouver
country: Canada
facility: University of British Columbia Department of Dermatology and Skin Science
state: British Columbia
city: Winnipeg
country: Canada
facility: Winnipeg Clinic
state: Manitoba
city: North York
country: Canada
facility: North York Research Inc.
state: Ontario
city: Oshawa
country: Canada
facility: Oshawa Clinic Dermatology Trials
state: Ontario
city: Richmond Hill
country: Canada
facility: York Dermatology Clinic and Research Centre
state: Ontario
city: Toronto
country: Canada
facility: Research Toronto
state: Ontario
city: Sherbrooke
country: Canada
facility: Diex Recherche Sherbrooke Inc.
state: Quebec
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
city: Chongqing
country: China
facility: The Second Affiliated Hospital of Army Medical University, PLA
state: Chongqing
city: Shenzhen
country: China
facility: The University of Hong Kong - Shenzhen Hospital
state: Guangdong
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital, Dermatological Department
city: Nachod
country: Czechia
facility: Dermamedica S.R.O.
city: Nachod
country: Czechia
facility: Oblastni nemocnice Nachod a.s., Radiodiagnosticke oddeleni
city: Nachod
country: Czechia
facility: Lekarna u Stribrneho orla
city: Praha 1
country: Czechia
facility: Sanatorium profesora Arenbergera
city: Praha 2
country: Czechia
facility: Lekarna U sv. Ignace
city: Svitavy
country: Czechia
facility: Dermatologicka Ambulance
city: Svitavy
country: Czechia
facility: Lekarna na Hranicni
city: Bad Bentheim
country: Germany
facility: Fachklinik Bad Bentheim
city: Berlin
country: Germany
facility: ISA GmbH
city: Blankenfelde-Mahlow
country: Germany
facility: Fachärztliche Gemeinschaftspraxis für Dermatologie und Venerologie, Allergologie,
city: Frankfurt
country: Germany
facility: IKF Pneumologie GmbH & Co KG
city: Hamburg
country: Germany
facility: Klinische Forschung Hamburg GmbH
city: Münster
country: Germany
facility: Universitaet Muenster
city: Schwerin
country: Germany
facility: Klinische Forschung Schwerin GmbH
city: Budapest
country: Hungary
facility: SE AOK Bor, Nemikortani es Boronkologiai Klinika
city: Budapest
country: Hungary
facility: Budapest Főváros XIX. Kerületi Önkormányzat Kispesti Egészsegügyi Intézete
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Szolnok
country: Hungary
facility: ALLERGO-DERM BAKOS Kft.
city: Yokohama
country: Japan
facility: Queen's square Medical Facilities Queen's square Dermatology and Allergology
state: Kanagawa
city: Kamimashiki-gun
country: Japan
facility: Noguchi Dermatology Clinic
state: Kumamoto
city: Neyagawa
country: Japan
facility: Yoshioka Dermatology Clinic
state: Osaka
city: Sakai
country: Japan
facility: Kume Clinic
state: Osaka
city: Edogawa-ku
country: Japan
facility: Sumire Dermatology Clinic
state: Tokyo
city: Nakano-ku
country: Japan
facility: Matsuyama Dermatology Clinic
state: Tokyo
city: Fukuoka
country: Japan
facility: Hoshikuma Dermatology・Allergy Clinic
city: Saitama
country: Japan
facility: Sanrui Hifuka
city: Bucheon-si
country: Korea, Republic of
facility: Soon Chun Hyang University Bucheon Hospital
state: Gyeonggi-do
city: Bupyeong-gu
country: Korea, Republic of
facility: The Catholic University of Korea, Incheon St.Mary's Hospital
state: Incheon
city: Jung-gu
country: Korea, Republic of
facility: Inha University Hospital
state: Incheon
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei Univ. Health System
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Chung-Ang University Hospital
city: Seoul
country: Korea, Republic of
facility: Hallym university Kangnam Sacred Heart Hospital
city: Jelgava
country: Latvia
facility: Selga Freiberga private practice in dermatovenerology and cosmetology
city: Riga
country: Latvia
facility: Riga 1st Hospital, Clinic for Dermatology and STD
city: Riga
country: Latvia
facility: Aesthetic dermatology clinic of Prof. J. Kisis
city: Riga
country: Latvia
facility: Health Centre 4 Ltd. Diagnostics Centre
city: Riga
country: Latvia
facility: Health Centre 4 Ltd
city: Bialystok
country: Poland
facility: NZOZ Specjalistyczny Osrodek Dermatologiczny DERMAL s.c.
city: Białystok
country: Poland
facility: KLIMED Marek Klimkiewicz
city: Krakow
country: Poland
facility: Centrum Nowoczesnych Terapii "DOBRY LEKARZ" sp. z o. o.
city: Kraków
country: Poland
facility: Centrum Badań Klinicznych JCI
city: Kraków
country: Poland
facility: Krakowskie Centrum Medyczne Sp. z o.o.
city: Lodz
country: Poland
facility: Centrum Terapii Wspolczesnej J.M. Jasnorzewska Spolka Komandytowo-Akcyjna
city: Lublin
country: Poland
facility: KO-MED Centra Kliniczne Lublin II
city: Poznan
country: Poland
facility: Clinical Research Center Sp. z o.o. MEDIC-R Sp. k.
city: Szczecin
country: Poland
facility: Twoja Przychodnia - Szczecinskie Centrum Medyczne
city: Warszawa
country: Poland
facility: Synexus Polska Sp. z o. o. Oddzial w Warszawie
city: Warszawa
country: Poland
facility: Centrum Medyczne AMED
city: Warszawa
country: Poland
facility: MTZ Clinical Research Sp. z o.o.
city: Warszawa
country: Poland
facility: Klinika Ambroziak Sp. z o.o.
city: Wroclaw
country: Poland
facility: Synexus Polska Sp. z o.o. Oddzial we Wroclawiu
city: Wrocław
country: Poland
facility: Lukasz Matusiak "4HEALTH"
city: Plymouth
country: United Kingdom
facility: Plymouth Hospitals NHS Trust, Derriford Hospital
state: Devon
city: Blackpool
country: United Kingdom
facility: MAC Clinical Research
state: Lancashire
city: Cannock
country: United Kingdom
facility: MAC Clinical Research Ltd
state: South Staffordshire
city: Barnsley
country: United Kingdom
facility: Barnsley Hospital NHS Foundation Trust
state: South Yorkshire
city: Bristol
country: United Kingdom
facility: University Hospital Bristol NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: MAC Clinical Research Ltd
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Blauvelt A, Boguniewicz M, Brunner PM, Luna PC, Biswas P, DiBonaventura M, Farooqui SA, Rojo R, Cameron MC. Abrocitinib monotherapy in Investigator's Global Assessment nonresponders: improvement in signs and symptoms of atopic dermatitis and quality of life. J Dermatolog Treat. 2022 Aug;33(5):2605-2613. doi: 10.1080/09546634.2022.2059053. Epub 2022 Jul 6.
citation: Stander S, Bhatia N, Gooderham MJ, Silverberg JI, Thyssen JP, Biswas P, DiBonaventura M, Romero W, Farooqui SA. High threshold efficacy responses in moderate-to-severe atopic dermatitis are associated with additional quality of life benefits: pooled analyses of abrocitinib monotherapy studies in adults and adolescents. J Eur Acad Dermatol Venereol. 2022 Aug;36(8):1308-1317. doi: 10.1111/jdv.18170. Epub 2022 May 6.
citation: Wojciechowski J, Malhotra BK, Wang X, Fostvedt L, Valdez H, Nicholas T. Population pharmacokinetic-pharmacodynamic modelling of platelet time-courses following administration of abrocitinib. Br J Clin Pharmacol. 2022 Aug;88(8):3856-3871. doi: 10.1111/bcp.15334. Epub 2022 Apr 11.
citation: Wojciechowski J, Malhotra BK, Wang X, Fostvedt L, Valdez H, Nicholas T. Population Pharmacokinetics of Abrocitinib in Healthy Individuals and Patients with Psoriasis or Atopic Dermatitis. Clin Pharmacokinet. 2022 May;61(5):709-723. doi: 10.1007/s40262-021-01104-z. Epub 2022 Jan 21.
citation: Cork MJ, McMichael A, Teng J, Valdez H, Rojo R, Chan G, Zhang F, Myers DE, DiBonaventura M. Impact of oral abrocitinib on signs, symptoms and quality of life among adolescents with moderate-to-severe atopic dermatitis: an analysis of patient-reported outcomes. J Eur Acad Dermatol Venereol. 2022 Mar;36(3):422-433. doi: 10.1111/jdv.17792. Epub 2021 Dec 4.
citation: Simpson EL, Silverberg JI, Nosbaum A, Winthrop KL, Guttman-Yassky E, Hoffmeister KM, Egeberg A, Valdez H, Zhang M, Farooqui SA, Romero W, Thorpe AJ, Rojo R, Johnson S. Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program. Am J Clin Dermatol. 2021 Sep;22(5):693-707. doi: 10.1007/s40257-021-00618-3. Epub 2021 Aug 18.
citation: Silverberg JI, Thyssen JP, Simpson EL, Yosipovitch G, Stander S, Valdez H, Rojo R, Biswas P, Myers DE, Feeney C, DiBonaventura M. Impact of Oral Abrocitinib Monotherapy on Patient-Reported Symptoms and Quality of Life in Adolescents and Adults with Moderate-to-Severe Atopic Dermatitis: A Pooled Analysis of Patient-Reported Outcomes. Am J Clin Dermatol. 2021 Jul;22(4):541-554. doi: 10.1007/s40257-021-00604-9. Epub 2021 May 5.
citation: Silverberg JI, Simpson EL, Thyssen JP, Gooderham M, Chan G, Feeney C, Biswas P, Valdez H, DiBonaventura M, Nduaka C, Rojo R. Efficacy and Safety of Abrocitinib in Patients With Moderate-to-Severe Atopic Dermatitis: A Randomized Clinical Trial. JAMA Dermatol. 2020 Aug 1;156(8):863-873. doi: 10.1001/jamadermatol.2020.1406.