Clinical trial NCT02974868: Study To Evaluate The Efficacy And Safety Profile Of PF-06651600 And PF-06700841 In Subjects With Alopecia Areata
Official title: A PHASE 2A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY PROFILE OF PF-06651600 AND PF-06700841 IN SUBJECTS WITH MODERATE TO SEVERE ALOPECIA AREATA WITH A SINGLE-BLIND EXTENSION PERIOD AND A CROSS-OVER OPEN LABEL EXTENSION PERIOD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alopecia Areata
Keywords: Phase 2
randomized
double-blind
placebo
alopecia areata
safety
efficacy
JAK
janus kinase
moderate
severe
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2016-11-29
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model description: The first 24 weeks are parallel. The single-blind extension period will have a segment for non-responder and a withdrawal/retreatment segment for responder. The cross-over extension period is parallel for non-responders.
Primary purpose: TREATMENT

Brief summary: This is a Phase 2a, randomized, double blind, parallel group, multicenter study with an extension period. The study will have a maximum duration of approximately 113 weeks. This includes an up to 5 weeks Screening Period, a 24 week Treatment Period, a 4 week Drug Holiday (#1), an up to 12 month Single Blind (investigator open, sponsor open and subject blind) Extension Period, a 4 week drug holiday (#2), a 6 month Cross Over Open Label Extension Period and a 4 week Follow up Period.


Eligibility criteria: Inclusion Criteria:

* Male or female subjects between 18 75 years of age, inclusive, at time of informed consent.
* Must have moderate to severe alopecia areata:

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 2 week of first dose of study drug: Topical treatments that could affect AA; Herbal medications with unknown properties or known beneficial effects for AA.

Primary outcomes:
measure: Change From Baseline in Severity of Alopecia Tool (SALT) Score at Week 24
timeFrame: Baseline, Week24
measure: Number of Participants With Treatment-emergent Adverse Events (All-causality and Treatment-related) - Single-Blind Extension (SBE) Period
timeFrame: Week 28 up to Week 52
measure: Number of Participants With Treatment-emergent Adverse Events (All-causality and Treatment-related) - Cross-Over Extension (COE) Period
timeFrame: COE day 1 up to end of study
measure: Number of Participants With Laboratory Abnormalities During SBE Period
timeFrame: Week 28 up to Week 52 for non-responders and responders in the withdrawal segment, AT day 1 up to AT Week 24 for retreatment segment (AT=active treatment)
measure: Numbers of Participants With Specific Clinical Laboratory Abnormalities During COE Period
timeFrame: COE day 1 up to end of study
Secondary outcomes:
measure: Change From Baseline in Severity of Alopecia Tool (SALT) Score at Week 24 -AT/AU Participants
timeFrame: Baseline, Week 24
measure: Percentage of Participants Achieving SALT 30 at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Severity of Alopecia Tool (SALT) Across Time (Treatment Period)
timeFrame: Baseline, Weeks 2,4,6,8,12,16,20,24
measure: Percent Change From Baseline in Severity of Alopecia Tool (SALT) Across Time (Treatment Period)
timeFrame: Baseline, Weeks 2,4,6,8,12,16,20,24
measure: Percentage of Participants Achieving SALT 30 Across Time (Treatment Period)
timeFrame: Baseline, Weeks 2,4,6,8,12,16,20,24
measure: Percentage of Participants Achieving SALT 50 Across Time (Treatment Period)
timeFrame: Baseline, Weeks 2,4,6,8,12,16,20,24
measure: Percentage of Participants Achieving SALT 75 Across Time (Treatment Period)
timeFrame: Baseline, Weeks 2,4,6,8,12,16,20,24
measure: Percentage of Participants Achieving SALT 90 Across Time (Treatment Period)
timeFrame: Baseline, Weeks 2,4,6,8,12,16,20,24
measure: Percentage of Participants Achieving SALT 100 Across Time (Treatment Period)
timeFrame: Baseline, Weeks 2,4,6,8,12,16,20,24
measure: Number of Participants With the IGA Score Change (Treatment Period)
timeFrame: baseline, Week 2,4,6,8,12,16,20,24
measure: Number of Participants With Treatment-emergent Adverse Events (All-causality and Treatment-related) - Treatment Period
timeFrame: baseline up to Week 24
measure: Number of Participants With Laboratory Abnormalities During Treatment Period
timeFrame: Baseline up to Week 24
measure: Time to Achieve the Retreatment Criteria During the Withdrawal/Retreatment Part of the Extension Period Among Subjects Who Achieved Primary Endpoint at Week 24 (SBE Period)
timeFrame: Week 24 up to Week 52
measure: Change From Baseline in SALT Across Time (SBE Period)
timeFrame: Weeks 30, 32, 34, 36, 40, 44, 48, 52 for non-responders, and AT Weeks 2, 4, 6, 8, 12, 16, 20, 24 for retreated responders.(AT=active treatment)
measure: Percentage of Participants Achieving SALT 30 Across Time (SBE Period)
timeFrame: Weeks 30, 32, 34, 36, 40, 44, 48, 52 for non-responders, and AT Weeks 2, 4, 6, 8, 12, 16, 20, 24 for retreated responders.(AT=active treatment)
measure: Percentage of Participants Achieving SALT 50 Across Time (SBE Period)
timeFrame: Weeks 30, 32, 34, 36, 40, 44, 48, 52 for non-responders, and AT Weeks 2, 4, 6, 8, 12, 16, 20, 24 for retreated responders.(AT=active treatment)
measure: Percentage of Participants Achieving SALT 75 Across Time (SBE Period)
timeFrame: Weeks 30, 32, 34, 36, 40, 44, 48, 52 for non-responders, and AT Weeks 2, 4, 6, 8, 12, 16, 20, 24 for retreated responders.(AT=active treatment)
measure: Percentage of Participants Achieving SALT 90 Across Time (SBE Period)
timeFrame: Weeks 30, 32, 34, 36, 40, 44, 48, 52 for non-responders, and AT Weeks 2, 4, 6, 8, 12, 16, 20, 24 for retreated responders.(AT=active treatment)
measure: Percentage of Participants Achieving SALT 100 Across Time (SBE Period)
timeFrame: Weeks 30, 32, 34, 36, 40, 44, 48, 52 for non-responders, and AT Weeks 2, 4, 6, 8, 12, 16, 20, 24 for retreated responders.(AT=active treatment)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham, Dermatology at the Whitaker Clinic
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham, The Kirklin Clinic
state: Alabama
city: Santa Ana
country: United States
facility: Southern California Dermatology, Inc.
state: California
city: Santa Monica
country: United States
facility: Clinical Science Institute
state: California
city: Santa Monica
country: United States
facility: Office of F. Monte Purcelli
state: California
city: Santa Monica
country: United States
facility: Tower Saint John's Imaging
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital Clinical and Translational Research Center, Inpatient Unit
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital Clinical and Translational Research Center, Outpatient Clinic
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital, Anschutz Cancer Pavilion
state: Colorado
city: New Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
city: New Haven
country: United States
facility: Investigational Drug Services
state: Connecticut
city: New Haven
country: United States
facility: Church Street Research Unit
state: Connecticut
city: New Haven
country: United States
facility: Yale Hearing and Balance Center
state: Connecticut
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Orange Park
country: United States
facility: Park Avenue Dermatology Administrative Annex
state: Florida
city: Orange Park
country: United States
facility: Park Avenue Dermatology
state: Florida
city: Tampa
country: United States
facility: Edward B. Kampsen, MD
state: Florida
city: Tampa
country: United States
facility: Olympian Clinical Research
state: Florida
city: Tampa
country: United States
facility: Rose Radiology
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: 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: Boston
country: United States
facility: Massachusetts General Hospital Clinical Unit for Research Trials in Skin (CURTIS)
state: Massachusetts
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Mount Sinai Department of Otolaryngology
state: New York
city: New York
country: United States
facility: Rockefeller University Hospital
state: New York
city: Rochester
country: United States
facility: Investigational Drug Service
state: New York
city: Rochester
country: United States
facility: University of Rochester Audiology
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Radiology
state: New York
city: Tulsa
country: United States
facility: Vital Prospects Clinical Research Institute, P.C.
state: Oklahoma
city: Rapid City
country: United States
facility: Health Concepts
state: South Dakota
city: Murray
country: United States
facility: University of Utah MidValley Dermatology
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Medical Center
state: Utah
city: Norfolk
country: United States
facility: Virginia Clinical Research, Inc.
state: Virginia
city: Hurstville
country: Australia
facility: Hearing Life
state: New South Wales
city: Kogarah
country: Australia
facility: Dr. Glen and Partners Medical Imaging
state: New South Wales
city: Kogarah
country: Australia
facility: St George Dermatology and Skin Cancer Centre
state: New South Wales
city: Kogarah
country: Australia
facility: St. George Hearing and Balance Clinic
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: Carlton
country: Australia
facility: Skin & Cancer Foundation Inc.
state: Victoria
city: East Melbourne
country: Australia
facility: Sinclair Dermatology
state: Victoria
city: Richmond
country: Australia
facility: Bridge Road Imag ing
state: Victoria
city: Richmond
country: Australia
facility: Richmond Audiology
state: Victoria
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: Richmond Hill
country: Canada
facility: York Dermatology Center
state: Ontario
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Hughes JH, Qiu R, Banfield C, Dowty ME, Nicholas T. Population Pharmacokinetics of Oral Brepocitinib in Healthy Volunteers and Patients. Clin Pharmacol Drug Dev. 2022 Dec;11(12):1447-1456. doi: 10.1002/cpdd.1163. Epub 2022 Aug 31.
citation: Peeva E, Guttman-Yassky E, Banerjee A, Sinclair R, Cox LA, Zhu L, Zhu H, Vincent M, King B. Maintenance, withdrawal, and re-treatment with ritlecitinib and brepocitinib in patients with alopecia areata in a single-blind extension of a phase 2a randomized clinical trial. J Am Acad Dermatol. 2022 Aug;87(2):390-393. doi: 10.1016/j.jaad.2021.12.008. Epub 2021 Dec 13. No abstract available.
citation: Guttman-Yassky E, Pavel AB, Diaz A, Zhang N, Del Duca E, Estrada Y, King B, Banerjee A, Banfield C, Cox LA, Dowty ME, Page K, Vincent MS, Zhang W, Zhu L, Peeva E. Ritlecitinib and brepocitinib demonstrate significant improvement in scalp alopecia areata biomarkers. J Allergy Clin Immunol. 2022 Apr;149(4):1318-1328. doi: 10.1016/j.jaci.2021.10.036. Epub 2021 Dec 1.
citation: Fensome A, Ambler CM, Arnold E, Banker ME, Brown MF, Chrencik J, Clark JD, Dowty ME, Efremov IV, Flick A, Gerstenberger BS, Gopalsamy A, Hayward MM, Hegen M, Hollingshead BD, Jussif J, Knafels JD, Limburg DC, Lin D, Lin TH, Pierce BS, Saiah E, Sharma R, Symanowicz PT, Telliez JB, Trujillo JI, Vajdos FF, Vincent F, Wan ZK, Xing L, Yang X, Yang X, Zhang L. Dual Inhibition of TYK2 and JAK1 for the Treatment of Autoimmune Diseases: Discovery of (( S)-2,2-Difluorocyclopropyl)((1 R,5 S)-3-(2-((1-methyl-1 H-pyrazol-4-yl)amino)pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methanone (PF-06700841). J Med Chem. 2018 Oct 11;61(19):8597-8612. doi: 10.1021/acs.jmedchem.8b00917. Epub 2018 Aug 16.