Clinical trial NCT02780167: Study To Evaluate Pf-04965842 In Subjects With Moderate To Severe Atopic Dermatitis
Official title: A PHASE 2B RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL, MULTICENTER, DOSE-RANGING, STUDY TO EVALUATE THE EFFICACY AND SAFETY PROFILE OF PF-04965842 IN SUBJECTS WITH MODERATE TO SEVERE ATOPIC DERMATITIS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atopic Dermatitis
Keywords: Phase 2
randomized
double-blind
placebo
atopic dermatitis
safety
efficacy
JAK
janus kinase
moderate
severe
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2016-05-23
Enrollment: 269
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Study B7451006 is a Phase 2b POC study which is planned to assess four PF 04965842 once daily (QD) doses (10, 30, 100, 200 mg) relative to placebo over 12 weeks to characterize the efficacy and safety of PF 04965842 in subjects with moderate to severe AD. The objectives of the study are to demonstrate the efficacy of PF 04965842 by showing improvement in disease severity in patients with moderate to severe AD as measured by the Investigator's Global Assessment (IGA) and Eczema Area and Severity Index (EASI) scores, and safety to support further clinical development of PF 04965842.


Eligibility criteria: Inclusion Criteria:

* Male or female subjects between 18 75 years of age, inclusive, at time of informed consent.
* Must have the following atopic dermatitis criteria:

  1. Have a clinical diagnosis of chronic atopic dermatitis (also known as atopic eczema) for at least 1 year prior to Day 1 and has confirmed atopic dermatitis (Hanifin and Rajka criteria of AD refer to Appendix 2) at the Screening visit.
  2. Have inadequate response to treatment with topical medications given for at least 4 weeks, or for whom topical treatments are otherwise medically inadvisable (eg, because of important side effects or safety risks) within 12 months of the first dose of study drug.
  3. Moderate to severe AD (affected BSA \>=10 %, IGA \>=3, and EASI \>=12 at the screening and baseline visits).

Exclusion Criteria:

* History of human immunodeficiency virus (HIV) or positive HIV serology at screening,
* Infected with hepatitis B or hepatitis C viruses.
* Have evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB)
* Have received any of the following treatment regiments specified in the timeframes outlined below:

Within 6 months of first dose of study drug: Any cell depleting agents Within 12 weeks of first dose of study drug: Any studies with JAK inhibitors; Other biologics Within 8 weeks of first dose of study drug: Participation in other studies involving investigational drug(s) Within 6 weeks of first dose of study drug: Have been vaccinated with live or attenuated live vaccine.

Within 4 weeks of first dose of study drug: Use of oral immune suppressants; Phototherapy (NB UVB) or broad band phototherapy; Regular use (more than 2 visits per week) of a tanning booth/parlor.

Within 1 week of first dose of study drug: Topical treatments that could affect atopic dermatitis; Herbal medications with unknown properties or known beneficial effects for AD.

Primary outcomes:
measure: Percentage of Participants Achieving the Investigator's Global Assessment (IGA) for Clear (0) or Almost Clear (1) and >=2 Points Improvement From Baseline at Week 12
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Percent Change From Baseline in the Eczema Area and Severity Index (EASI) at Week 12
timeFrame: Baseline and Week 12
measure: Percentage of Participants Achieving the IGA for Clear (0) or Almost Clear (1) and >=2 Points Improvement From Baseline at All Scheduled Time Points Except Week 12
timeFrame: Baseline and all scheduled time points except Week 12, including Weeks 1, 2, 4, 6, 8, 13, 14, 16.
measure: Percentage of Participants Achieving >=2 Points Improvement in the IGA From Baseline at All Scheduled Time Points
timeFrame: Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 13, 14, 16
measure: Percent Change From Baseline in the EASI Total Score at All Scheduled Time Points Except Week 12.
timeFrame: Baseline and all scheduled time points except Week 12, including Weeks 1, 2, 4, 6, 8, 13, 14, 16
measure: Percentage of Participants Achieving >=3 Points Improvement in the Pruritus Numerical Rating Scale (NRS) From Baseline at All Scheduled Time Points
timeFrame: Baseline and all scheduled time points, including Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 29, 43, 57, 85, 99, 113
measure: Percentage of Participants Achieving >=4 Points Improvement in the Pruritus NRS From Baseline at All Scheduled Time Points
timeFrame: Baseline and all scheduled time points, including Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 29, 43, 57, 85, 99, 113
measure: Time to Achieving >=3 Points Improvement in NRS
timeFrame: Baseline till Week 16
measure: Time to Achieving >=4 Points Improvement in NRS
timeFrame: Baseline till Week 16
measure: Percent Change From Baseline in the Pruritus NRS From Baseline at All Scheduled Time Points
timeFrame: Baseline and all scheduled time points, including Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 29, 43, 57, 85, 99, 113
measure: Change From Baseline in Pruritus NRS Score at All Scheduled Time Points
timeFrame: Baseline and all scheduled time points, including Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 29, 43, 57, 85, 99, 113
measure: Percentage of Participants Achieving a >=50% Improvement in the EASI Total Score (EASI50) at All Scheduled Time Points
timeFrame: All scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 13, 14, 16
measure: Percentage of Participants Achieving a >=75% Improvement in the EASI Total Score (EASI75) at All Scheduled Time Points
timeFrame: All scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 13, 14, 16
measure: Percentage of Participants Achieving a >=90% Improvement in the EASI Total Score (EASI90) at All Scheduled Time Points
timeFrame: All scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 13, 14, 16
measure: Change From Baseline in Affected BSA at All Scheduled Time Points
timeFrame: Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 13, 14, 16
measure: Change From Baseline in Scoring Atopic Dermatitis (SCORAD) at All Scheduled Time Points
timeFrame: Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 13, 14, 16
measure: Percent Change From Baseline in SCORAD at All Scheduled Time Points
timeFrame: Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 13, 14, 16
measure: Percentage of Participants Achieving a >=50% Improvement in SCORAD (SCORAD50) From Baseline at All Scheduled Time Points
timeFrame: Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 13, 14, 16
measure: Percentage of Participants Achieving a >=75% Improvement in SCORAD (SCORAD75) From Baseline at All Scheduled Time Points
timeFrame: Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 13, 14, 16
measure: Number of Participants With Treatment-emergent Adverse Events (AEs)
timeFrame: Baseline till Week 16
measure: Number of Participants With Specific Clinical Laboratory Abnormalities (Anemia, Neutropenia, Thrombocytopenia, Lymphopenia, Lipid Profile, Liver Function Tests (LFTs)
timeFrame: Baseline up to Week 16
measure: Percentage of Participants With Patient Global Assessment (PtGA) of AD of Clear (0) or Almost Clear (1) and >=2 Points Improvement From Baseline at All Scheduled Time Points
timeFrame: Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 14, 16
measure: Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at All Scheduled Time Points
timeFrame: Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 14, 16
measure: Change From Baseline in Patient Oriented Eczema Measure (POEM) at All Scheduled Time Points
timeFrame: Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 14, 16
measure: Change From Baseline in the Hospital and Anxiety Depression Scale (HADS) at All Scheduled Time Points
timeFrame: Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 14, 16
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Clinical Research Center of Alabama
state: Alabama
city: Encinitas
country: United States
facility: California Dermatology & Clinical Research Institute
state: California
city: Pasadena
country: United States
facility: Huntington Medical Foundation
state: California
city: Rolling Hills Estates
country: United States
facility: Peninsula Research Associates, Inc.
state: California
city: Sacramento
country: United States
facility: Emil A. Tanghetti MD dba Center for Dermatology and Laser Surgery
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: Farmington
country: United States
facility: University of Connecticut Health Center (UConn Health)
state: Connecticut
city: Clearwater
country: United States
facility: Olympian Clinical Research
state: Florida
city: Jacksonville
country: United States
facility: North Florida Dermatology Associates, PA
state: Florida
city: Orange Park
country: United States
facility: Park Avenue Dermatology Administration Annex
state: Florida
city: Orange Park
country: United States
facility: Park Avenue Dermatology
state: Florida
city: Ormond Beach
country: United States
facility: Leavitt Medical Associates of Florida d/b/a Ameriderm Research
state: Florida
city: Tampa
country: United States
facility: Forward Clinical Trials, Inc.
state: Florida
city: Newnan
country: United States
facility: MedaPhase, Inc.
state: Georgia
city: West Dundee
country: United States
facility: Dundee Dermatology
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: Plainfield
country: United States
facility: The Indiana Clinical Trials Center
state: Indiana
city: Louisville
country: United States
facility: DS Research
state: Kentucky
city: Lake Charles
country: United States
facility: Shondra L Smith, MD Dermatology & Advanced Aesthetics
state: Louisiana
city: Troy
country: United States
facility: Somerset Skin Centre
state: Michigan
city: Saint Joseph
country: United States
facility: MediSearch Clinical Trials
state: Missouri
city: Las Vegas
country: United States
facility: Clinical Research Consortium
state: Nevada
city: East Windsor
country: United States
facility: Psoriasis Treatment Center of Central New Jersey
state: New Jersey
city: Verona
country: United States
facility: The Dermatology Group, P.C
state: New Jersey
city: Forest Hills
country: United States
facility: Forest Hills Dermatology Group
state: New York
city: New York
country: United States
facility: Sadick Research Group
state: New York
city: Tulsa
country: United States
facility: Vital Prospects Clinical Research Institute, P.C
state: Oklahoma
city: Hazleton
country: United States
facility: DermDox Centers for Dermatology
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Department of Dermatology
state: Pennsylvania
city: Johnston
country: United States
facility: Clinical Partners, LLC
state: Rhode Island
city: Rapid City
country: United States
facility: Health Concepts
state: South Dakota
city: Bellaire
country: United States
facility: Bellaire Dermatology Associates
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: Richmond
country: United States
facility: West End Dermatology Associates
state: Virginia
city: Phillip
country: Australia
facility: Woden Dermatology
state: Australian Capital Territory
city: Sydney
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
state: Queensland
city: East Melbourne
country: Australia
facility: Sinclair Dermatology
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Fremantle
country: Australia
facility: Fremantle Dermatology
state: Western Australia
city: Hectorville, South Australia
country: Australia
facility: North Eastern Health Specialists
city: Vancouver
country: Canada
facility: University of British Columbia
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: Oakville
country: Canada
facility: Research by ICLS
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: Waterloo
country: Canada
facility: K. Papp Clinical Research
state: Ontario
city: Windsor
country: Canada
facility: Windsor Clinical Research Inc
state: Ontario
city: Montreal
country: Canada
facility: Innovaderm Research Inc.
state: Quebec
city: Sherbrooke
country: Canada
facility: Diex Research Sherbrooke Inc.
state: Quebec
city: Quebec
country: Canada
facility: Centre de Recherche Dermatologique du Quebec metropolitain (CRDQ)
city: Berlin
country: Germany
facility: ISA GmbH
city: Luebeck
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein
city: Muenster
country: Germany
facility: Universitaetsklinikum Muenster
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
city: Kecskemet
country: Hungary
facility: Bacs Kiskun Megyei Korhaz, Bor es Nemibeteggondozo
city: Miskolc
country: Hungary
facility: CRU Hungary Ltd., MISEK-CRU
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem SzentGyorgyi Albert Klinikai Kozpont Borgyogyaszati es Allergologiai Klinika
city: Szolnok
country: Hungary
facility: Allergo-Derm Bakos Kft.
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Gooderham MJ, Girolomoni G, Moore JO, Silverberg JI, Bissonnette R, Forman S, Peeva E, Biswas P, Valdez H, Chan G. Durability of Response to Abrocitinib in Patients with Moderate-to-Severe Atopic Dermatitis After Treatment Discontinuation in a Phase 2b Trial. Dermatol Ther (Heidelb). 2022 Sep;12(9):2077-2085. doi: 10.1007/s13555-022-00764-4. Epub 2022 Aug 7.
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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: 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, Wollenberg A, Bissonnette R, Silverberg JI, Papacharalambous J, Zhu L, Zhang W, Beebe JS, Vincent M, Peeva E, Bushmakin AG, Cappelleri JC, Chen L, Sikirica V, Xenakis J. Patient-Reported Symptoms and Disease Impacts in Adults With Moderate-to-Severe Atopic Dermatitis: Results From a Phase 2b Study With Abrocitinib. Dermatitis. 2021 Oct 1;32(1S):S53-S61. doi: 10.1097/DER.0000000000000725.
citation: Gooderham MJ, Forman SB, Bissonnette R, Beebe JS, Zhang W, Banfield C, Zhu L, Papacharalambous J, Vincent MS, Peeva E. Efficacy and Safety of Oral Janus Kinase 1 Inhibitor Abrocitinib for Patients With Atopic Dermatitis: A Phase 2 Randomized Clinical Trial. JAMA Dermatol. 2019 Dec 1;155(12):1371-1379. doi: 10.1001/jamadermatol.2019.2855.