Clinical trial NCT03349060: Study to Evaluate 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: 2017-11-21
Enrollment: 387
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: B7451012 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 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 (EASI) Response of >=75 Percent (%) Improvement From Baseline at Week 12
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Percentage of Participants With at Least 4 Points Improvement From Baseline in the Numerical Rating Scale (NRS) for Severity of Pruritus at Week 2, 4, 8 and 12: Full Analysis Set (FAS)
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Percentage of Participants With at Least 4 Points Improvement From Baseline in the Numerical Rating Scale for Severity of Pruritus at Week 2, 4 and 12: Per Protocol Analysis Set (PPAS)
timeFrame: Baseline, Week 2, 4, 12
measure: Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) Total Score at Week 2, 4, 8 and 12: Full Analysis Set
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis Total Score at Week 12: Per Protocol Analysis Set
timeFrame: Baseline, Week 12
measure: Time to Achieve >=4 Points Improvement From Baseline in Numerical Rating Scale for Severity of Pruritus
timeFrame: Baseline up to Week 12
measure: Percentage of Participants Achieving Eczema Area and Severity Index Response of >=75% Improvement From Baseline at Week 2, 4 and 8
timeFrame: Baseline, Week 2, 4, 8
measure: Percentage of Participants Achieving Investigator's Global Assessment Response of Clear (0) or Almost Clear (1) and >=2 Points Improvement From Baseline at Week 2, 4 and 8
timeFrame: Baseline, Week 2, 4, 8
measure: Percentage of Participants Achieving Investigator's Global Assessment Response of Clear (0) at Week 2, 4, 8 and 12
timeFrame: Week 2, 4, 8, 12
measure: Percentage of Participants Achieving Eczema Area and Severity Index Response of >=50% Improvement From Baseline at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Percentage of Participants Achieving Eczema Area and Severity Index Response of >=90% Improvement From Baseline at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Percentage of Participants Achieving Eczema Area and Severity Index Response of 100% Improvement From Baseline at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Change From Baseline in Eczema Area and Severity Index Total Score at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Change From Baseline in Percentage Body Surface Area at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Percentage of Participants With Percentage Body Surface Area Less Than (<) 5% at Week 2, 4, 8 and 12
timeFrame: Week 2, 4, 8, 12
measure: Percentage of Participants With Scoring Atopic Dermatitis (SCORAD) Response of >=50% Improvement From Baseline at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Percentage of Participants With Scoring Atopic Dermatitis Response of >=75% Improvement From Baseline at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Change From Baseline in Scoring Atopic Dermatitis: Visual Analogue Scale of Sleep Loss at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Change From Baseline in Scoring Atopic Dermatitis: Total Score at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Percentage of Participants Achieving >=1 Point Improvement From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Percentage of Participants With Baseline Dermatology Life Quality Index Score >=2 and Achieving <2 DLQI Score at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Percentage of Participants With Baseline Children's Dermatology Life Quality Index Score >=2 and Achieving <2 CDLQI Score at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Percentage of Participants With Baseline Dermatology Life Quality Index Score >=4 and Achieving >=4 Point Improvement From Baseline in DLQI Score at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Percentage of Participants With Baseline Children's Dermatology Life Quality Index Score >=2.5 and Achieving >=2.5 Point Improvement From Baseline in CDLQI Score at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Change From Baseline in Hospital Anxiety and Depression Scale (HADS): Depression Subscale at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Change From Baseline in Hospital Anxiety and Depression Scale: Anxiety Subscale at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Percentage of Participants With >=8 Points at Baseline and Achieving Score of <8 Points in Hospital Anxiety and Depression Scale: Anxiety Subscale at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Percentage of Participants With >=8 Points at Baseline and Achieving Score of <8 Points in Hospital Anxiety and Depression Scale: Depression Subscale at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Percentage of Participants With >=11 Points at Baseline and Achieving Score of <11 Points in Hospital Anxiety and Depression Scale: Anxiety Subscale at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Percentage of Participants With >=11 Points at Baseline and Achieving Score of <11 Points in Hospital Anxiety and Depression Scale: Depression Subscale at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Change From Baseline in Patient-Oriented Eczema Measure (POEM) at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Change From Baseline in Patient Global Assessment (PtGA) at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Percentage of Participants Achieving 'Clear' or 'Almost Clear' and >=2 Points Improvement From Baseline in Patient Global Assessment (PtGA) at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Change From Baseline in EuroQol Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L): Index Value at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Change From Baseline in EuroQol Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L)- Visual Analogue Scale Score at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Change From Baseline in EuroQol Quality of Life 5-Dimension Youth Scale (EQ-5D-Y): Index Value at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Change From Baseline in EuroQol Quality of Life 5-Dimension Youth Scale (EQ-5D-Y): Visual Analogue Scale Score at Week 2, 4, 8 and 12
timeFrame: Baseline, Week 2, 4, 8, 12
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F) at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Pediatric Functional Assessment of Chronic Illness Therapy Fatigue Scale (Peds-FACIT-F) at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Short Form-36v2 (SF-36v2) Acute Summary Score at Week 12: Physical Component Summary
timeFrame: Baseline, Week 12
measure: Change From Baseline in Short Form-36v2 Acute Summary Score at Week 12: Mental Component Summary
timeFrame: Baseline, Week 12
measure: Plasma Concentration Versus Time Summary of PF-04965842
timeFrame: Day 1 of Week 4: 0 hour(Pre-dose), 0.5 hours post-dose; Day 1 of Week 12: 0.5, 4 hours post-dose
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Clinical Research Center of Alabama, LLC
state: Alabama
city: Encinitas
country: United States
facility: California Dermatology & Clinical Research Institute
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital - San Diego/University of California, San Diego
state: California
city: San Diego
country: United States
facility: TCR Medical Corporation
state: California
city: Santa Monica
country: United States
facility: Clinical Science Institute
state: California
city: Coral Gables
country: United States
facility: Florida Academic Centers Research and Education, LLC
state: Florida
city: Largo
country: United States
facility: Olympian Clinical Research
state: Florida
city: Tampa
country: United States
facility: Forward Clinical Trials, Inc.
state: Florida
city: Savannah
country: United States
facility: Meridian Clinical Research, LLC
state: Georgia
city: Skokie
country: United States
facility: NorthShore University HealthSystem Dermatology Clinical Trials Unit
state: Illinois
city: Indianapolis
country: United States
facility: Dawes Fretzin Clinical Research Group, LLC
state: Indiana
city: Indianapolis
country: United States
facility: Dawes Fretzin Dermatology Group, LLC
state: Indiana
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Medical Center, New Center One
state: Michigan
city: Troy
country: United States
facility: Somerset Skin Centre
state: Michigan
city: Saint Joseph
country: United States
facility: MediSearch Clinical Trials
state: Missouri
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Tulsa
country: United States
facility: Vital Prospects Clinical Research Institute, P.C.
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Charleston
country: United States
facility: Medical University of South Carolina Investigational Drug Services
state: South Carolina
city: Charleston
country: United States
facility: MUSC SCTR Research Nexus Clinic and Laboratory
state: South Carolina
city: Arlington
country: United States
facility: Arlington Research Center, Inc.
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center Houston
state: Texas
city: San Antonio
country: United States
facility: Texas Dermatology and Laser Specialists
state: Texas
city: Norfolk
country: United States
facility: Virginia Clinical Research, Inc.
state: Virginia
city: Lakewood
country: United States
facility: Pace Dermatology Associates
state: Washington
city: Tacoma
country: United States
facility: MultiCare Allenmore Hospital
state: Washington
city: Tacoma
country: United States
facility: MultiCare Institute for Research and Innovation
state: Washington
city: Tacoma
country: United States
facility: Pace Dermatology Associates
state: Washington
city: Maroubra
country: Australia
facility: Australian Clinical Research Network (ACRN)
state: New South Wales
city: Maroubra
country: Australia
facility: Spectrum Medical Imaging
state: New South Wales
city: Upper Mount Gravatt
country: Australia
facility: Queensland X-Ray
state: Queensland
city: Woolloongabba
country: Australia
facility: Veracity Clinical Research Pty Ltd
state: Queensland
city: Camberwell
country: Australia
facility: Emeritus Research
state: Victoria
city: Carlton
country: Australia
facility: Skin and Cancer Foundation Inc
state: Victoria
city: East Melbourne
country: Australia
facility: Melbourne Radiology Clinic
state: Victoria
city: East Melbourne
country: Australia
facility: Sinclair Dermatology
state: Victoria
city: Parkville
country: Australia
facility: The Royal Children's Hospital
state: Victoria
city: Richmond
country: Australia
facility: Bridge Road Imaging
state: Victoria
city: Calgary
country: Canada
facility: Kirk Barber Research
state: Alberta
city: Calgary
country: Canada
facility: Institute for Skin Advancement
state: Alberta
city: Surrey
country: Canada
facility: Dr. Chih-ho Hong Medical Inc
state: British Columbia
city: Vancouver
country: Canada
facility: University of British Columbia Department of Dermatology and Skin Science
state: British Columbia
city: Winnipeg
country: Canada
facility: Wiseman Dermatology Research Inc.
state: Manitoba
city: Markham
country: Canada
facility: Lynderm Research Inc
state: Ontario
city: Peterborough
country: Canada
facility: SKiN Centre for Dermatology
state: Ontario
city: Richmond Hill
country: Canada
facility: The Centre for Dermatology
state: Ontario
city: Richmond Hill
country: Canada
facility: York Dermatology Center
state: Ontario
city: Toronto
country: Canada
facility: Research Toronto
state: Ontario
city: Montreal
country: Canada
facility: Innovaderm Research Inc.
state: Quebec
city: Sherbrooke
country: Canada
facility: Diex Research Sherbrooke Inc.
state: Quebec
city: Kutna Hora
country: Czechia
facility: Lekarna Na Vaclavskem namesti
city: Kutna Hora
country: Czechia
facility: Kozni ambulance Kutna Hora, s.r.o.
city: Ostrava - Poruba
country: Czechia
facility: Lekarna Fakultni Nemocnice Ostrava
city: Ostrava - Poruba
country: Czechia
facility: Fakultni Nemocnice Ostrava, Kozni oddeleni
city: Praha 1
country: Czechia
facility: Sanatorium profesora Arenbergera
city: Praha 2
country: Czechia
facility: Lekarna U sv. Ignace
city: Usti nad Labem
country: Czechia
facility: Krajska zdravotni a.s.,Masarykova nemocnice o.z.
city: Usti nad Labem
country: Czechia
facility: Lekarna Masarykovy nemocnice v Usti nad Labem, o.z.
city: Luebeck
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein/Campus Luebeck
state: Schleswig-holstein
city: Bad Bentheim
country: Germany
facility: Fachklinik Bad Bentheim
city: Berlin
country: Germany
facility: Charité - Universitaetsmedizin Berlin, CCM
city: Berlin
country: Germany
facility: ISA - Interdisciplinary Study Association GmbH
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus der Technischen Universitaet Dresden
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen, Hautklinik
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein, Campus Kiel
city: Munich
country: Germany
facility: Ludwig-Maximilians-University Munich
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Schwerin
country: Germany
facility: Klinische Forschung Schwerin GmbH
city: Kecskemet
country: Hungary
facility: Bács-Kiskun Megyei Kórház, Bőr-és nemibeteg Szakrendelés
state: Bács-kiskun
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont Borgyogyaszati Klinika
city: Kecskemet
country: Hungary
facility: Bacs-Kiskun Megyei Korhaz Kozponti Radiologiai Osztaly
city: Miskolc
country: Hungary
facility: CRU Hungary Ltd.
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem Klinikai Kozpont, Bor-,Nemikortani es Onkodermatologiai Klinika
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem Klinikai Kozpont
city: Katowice
country: Poland
facility: MULTIKLINIKA Salute Sp. z o.o.
city: Katowice
country: Poland
facility: Silmedic Sp. z o.o., Oddzial w Katowicach
city: Katowice
country: Poland
facility: Centrum Medyczne Angelius Provita
city: Katowice
country: Poland
facility: Pro Familia Altera Sp. z o.o.
city: Lodz
country: Poland
facility: NZOZ "DERMED" Centrum Medyczne Sp. z o.o. - Oddzial w Lodzi
city: Lodz
country: Poland
facility: Dermoklinika Centrum Medyczne s.c., M. Kierstan, J. Narbutt, A. Lesiak
city: Ostrowiec Swietokrzyski
country: Poland
facility: Dermedic Jacek Zdybski
city: Warszawa
country: Poland
facility: Wojskowy Instytut Medyczny, Klinika Dermatologiczna
city: Plymouth
country: United Kingdom
facility: Derriford Hospital, Plymouth Hospitals NHS Trust
state: Devon
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
state: Greater London
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
state: South Yorkshire, England
city: Sheffield
country: United Kingdom
facility: Sheffield Children's Hospital NHS Foundation Trust
state: South Yorkshire
city: Dudley
country: United Kingdom
facility: The Dudley Group NHS Foundation Trust
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.
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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: Simpson EL, Sinclair R, Forman S, Wollenberg A, Aschoff R, Cork M, Bieber T, Thyssen JP, Yosipovitch G, Flohr C, Magnolo N, Maari C, Feeney C, Biswas P, Tatulych S, Valdez H, Rojo R. Efficacy and safety of abrocitinib in adults and adolescents with moderate-to-severe atopic dermatitis (JADE MONO-1): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet. 2020 Jul 25;396(10246):255-266. doi: 10.1016/S0140-6736(20)30732-7.