Study To Evaluate The Efficacy And Safety Profile Of PF-06651600 And PF-06700841 In Subjects With Alopecia Areata
- Conditions
- Alopecia Areata
- Interventions
- Registration Number
- NCT02974868
- Lead Sponsor
- Pfizer
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 142
- Male or female subjects between 18 75 years of age, inclusive, at time of informed consent.
- Must have moderate to severe alopecia areata:
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Cohort 1 PF-06651600 PF-06651600 Cohort placebo Placebo placebo Cohort 2 PF-06700841 PF-06700841
- Primary Outcome Measures
Name Time Method Change From Baseline in Severity of Alopecia Tool (SALT) Score at Week 24 Baseline, Week24 SALT is a quantitative assessment of alopecia areata (AA) severity based on the scalp hair loss. Score range: 0-100%. Higher score indicates more severe disease. Change from baseline is defined as the baseline value minus the value at a specific visit. Positive change from baseline signifies an improvement. Baseline is defined as the last measurement prior to first dosing (Day 1).
Number of Participants With Treatment-emergent Adverse Events (All-causality and Treatment-related) - Single-Blind Extension (SBE) Period Week 28 up to Week 52 An AE (non-serious and serious) was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Any such events with initial onset or increasing in severity after the first dose of study treatment were counted as treatment-emergent Adverse Event (TEAE). Treatment-related TEAE were determined by investigators. Arms end with "withdrawal Segment" and "retreatment segment" described the same population while in different treatment segment .The reason why count on PF-06700841 differ by 1 participant is that 1 responder directly entered the retreatment segment and skipped the withdrawal segment.
Number of Participants With Treatment-emergent Adverse Events (All-causality and Treatment-related) - Cross-Over Extension (COE) Period COE day 1 up to end of study An AE (non-serious and serious) was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Any such events with initial onset or increasing in severity after the first dose of study treatment were counted as treatment-emergent Adverse Event (TEAE). Treatment-related TEAE were determined by investigators.
Number of Participants With Laboratory Abnormalities During SBE Period 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) Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology(Hemoglobin, Hematocrit, RBC count, Reticulocyte count, Platelet count, WBC count with differential, Total neutrophils, Eosinophils, Monocytes, Basophils, Lymphocytes); serum chemistry (BUN and Creatinine, Cystatin C, Creatine Phosphokinase, Glucose , Na+, K+, Cl ,Ca++, Total CO2, AST, ALT, Total Indirect \& Direct Bilirubin, Alkaline phosphatase, Uric acid, Albumin,Total protein, Fasting lipid Profile Panel; urinalysis(pH, Glucose, Protein, Nitrites, Leukocyte esterase, Microscopy culture);Other(HIV, HBsAg, HBcAb, HepB reflex (HbsAB), if applicable, HCVAb, Serum pregnancy test, Urine pregnancy test, FSH, QFT G or other IGRA, or PPD, EBV, CMV, HSV1, HSV2, VZV, Skin swab for herpetiform rash, Skin swab for potential drug related rash).Retest/discontinuation criteria are defined in Protocol Appendix 6.1 and 6.2 respectively.
Numbers of Participants With Specific Clinical Laboratory Abnormalities During COE Period COE day 1 up to end of study Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology(Hemoglobin, Hematocrit, RBC count, Reticulocyte count, Platelet count, WBC count with differential, Total neutrophils, Eosinophils, Monocytes, Basophils, Lymphocytes); serum chemistry (BUN and Creatinine, Cystatin C, Creatine Phosphokinase, Glucose , Na+, K+, Cl ,Ca++, Total CO2, AST, ALT, Total Indirect \& Direct Bilirubin, Alkaline phosphatase, Uric acid, Albumin,Total protein, Fasting lipid Profile Panel; urinalysis(pH, Glucose, Protein, Nitrites, Leukocyte esterase, Microscopy culture);Other(HIV, HBsAg, HBcAb, HepB reflex (HbsAB), if applicable, HCVAb, Serum pregnancy test, Urine pregnancy test, FSH, QFT G or other IGRA, or PPD, EBV, CMV, HSV1, HSV2, VZV, Skin swab for herpetiform rash, Skin swab for potential drug related rash).Retest/discontinuation criteria are defined in Protocol Appendix 6.1 and 6.2 respectively.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Severity of Alopecia Tool (SALT) Score at Week 24 -AT/AU Participants Baseline, Week 24 SALT is a quantitative assessment of alopecia areata (AA) severity based on the scalp hair loss. The SALT score can vary from 0 to 100%, with higher scores representing increasing severity of disease. Change from baseline is defined as the baseline value minus the value at a specific visit. Positive change from baseline implies an improvement. Alopecia totalis (AT): derived as SALT score = 100% at baseline only. Alopecia universalis (AU): derived as SALT score = 100% and both eyelash and eyebrow assessments were "none" at baseline.
Percentage of Participants Achieving SALT 30 at Week 24 Baseline, Week 24 SALT is a quantitative assessment of alopecia areata (AA) severity based on the scalp hair loss. A SALT 30 response is a 30% or greater reduction from baseline in SALT score. The SALT score can vary from 0 to 100%, with higher scores representing increasing severity of disease. The analysis was done using FAS (full analysis set) based on Non-responder imputation (ie. set missing values to be non-responsive) data. The 90% CI was calculated using Chan and Zhang method.
Change From Baseline in Severity of Alopecia Tool (SALT) Across Time (Treatment Period) Baseline, Weeks 2,4,6,8,12,16,20,24 SALT is a quantitative assessment of alopecia areata (AA) severity based on the scalp hair loss. The SALT score can vary from 0 to 100% with higher score indicates more severe disease. Baseline is defined as the last measurement prior to first dosing (Day 1). Change from baseline is defined as the baseline value minus the value at a specific visit. Positive change from baseline implies an improvement. Least Square Mean and 90% Confidence Interval of Arms (PF-06651600 and PF-06700841) are the Least Square Mean and 90% Confidence Interval for difference from placebo respectively.
Percent Change From Baseline in Severity of Alopecia Tool (SALT) Across Time (Treatment Period) Baseline, Weeks 2,4,6,8,12,16,20,24 SALT is a quantitative assessment of alopecia areata (AA) severity based on the scalp hair loss. The SALT score can vary from 0 to 100% with higher score indicates more severe disease. Baseline is defined as the last measurement prior to first dosing (Day 1). Percent change from baseline is defined as SALT baseline value minus SALT value at a specific visit divided by baseline and multiplying by 100. Positive change from baseline implies an improvement. Least Square Mean and 90% Confidence Interval of Arms (PF-06651600 and PF-06700841) are the Least Square Mean and 90% Confidence Interval for difference from placebo respectively.
Percentage of Participants Achieving SALT 30 Across Time (Treatment Period) Baseline, Weeks 2,4,6,8,12,16,20,24 SALT is a quantitative assessment of alopecia areata (AA) severity based on the scalp hair loss. A SALT 30 response is a 30% or greater reduction from baseline in SALT score. The SALT score can vary from 0 to 100%, with higher scores representing increasing severity of disease. The analysis was done using FAS (full analysis set) based on Non-responder imputation (ie. set missing values to be non-responsive) data. The percentage(Number) and 90% confidence interval (CI) of Arms(PF-06651600 and PF-06700841) in this outcome measurement is the percentage and 90% CI for difference from placebo. The 90% CI was calculated using Chan and Zhang method.
Percentage of Participants Achieving SALT 50 Across Time (Treatment Period) Baseline, Weeks 2,4,6,8,12,16,20,24 SALT is a quantitative assessment of alopecia areata (AA) severity based on the scalp hair loss. A SALT 50 response is a 50% or greater reduction from baseline in SALT score. The SALT score can vary from 0 to 100%, with higher scores representing increasing severity of disease. The analysis was done using FAS (full analysis set) based on Non-responder imputation (ie. set missing values to be non-responsive) data. The percentage(Number) and 90% confidence interval (CI) of Arms(PF-06651600 and PF-06700841) in this outcome measurement is the percentage and 90% CI for difference from placebo. The 90% CI was calculated using Chan and Zhang method.
Percentage of Participants Achieving SALT 75 Across Time (Treatment Period) Baseline, Weeks 2,4,6,8,12,16,20,24 SALT is a quantitative assessment of alopecia areata (AA) severity based on the scalp hair loss. A SALT 75 response is a 75% or greater reduction from baseline in SALT score. The SALT score can vary from 0 to 100%, with higher scores representing increasing severity of disease. The analysis was done using FAS (full analysis set) based on Non-responder imputation (ie. set missing values to be non-responsive) data. The percentage(Number) and 90% confidence interval (CI) of Arms(PF-06651600 and PF-06700841) in this outcome measurement is the percentage and 90% CI for difference from placebo. The 90% CI was calculated using Chan and Zhang method.
Percentage of Participants Achieving SALT 90 Across Time (Treatment Period) Baseline, Weeks 2,4,6,8,12,16,20,24 SALT is a quantitative assessment of alopecia areata (AA) severity based on the scalp hair loss. A SALT 90 response is a 90% or greater reduction from baseline in SALT score. The SALT score can vary from 0 to 100%, with higher scores representing increasing severity of disease. The analysis was done using FAS (full analysis set) based on Non-responder imputation (ie. set missing values to be non-responsive) data. The percentage(Number) and 90% confidence interval (CI) of Arms(PF-06651600 and PF-06700841) in this outcome measurement is the percentage and 90% CI for difference from placebo. The 90% CI was calculated using Chan and Zhang method.
Percentage of Participants Achieving SALT 100 Across Time (Treatment Period) Baseline, Weeks 2,4,6,8,12,16,20,24 SALT is a quantitative assessment of alopecia areata (AA) severity based on the scalp hair loss. A SALT 100 response is a 100% or greater reduction from baseline in SALT score. The SALT score can vary from 0 to 100%, with higher scores representing increasing severity of disease. The analysis was done using FAS (full analysis set) based on Non-responder imputation (ie. set missing values to be non-responsive) data. The percentage(Number) and 90% confidence interval (CI) of Arms(PF-06651600 and PF-06700841) in this outcome measurement is the percentage and 90% CI for difference from placebo. The 90% CI was calculated using Chan and Zhang method.
Number of Participants With the IGA Score Change (Treatment Period) baseline, Week 2,4,6,8,12,16,20,24 The clinical evaluator of alopecia areata (AA) will perform an assessment of the overall improvement of AA and assign an Investigator Global Assessment (IGA) score(ranging from 0 to 5) with higher score representing higher regrowth rate. Baseline is defined as the last measurement prior to first dosing (Day 1).
Number of Participants With Treatment-emergent Adverse Events (All-causality and Treatment-related) - Treatment Period baseline up to Week 24 An AE (non-serious and serious) was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Any such events with initial onset or increasing in severity after the first dose of study treatment were counted as treatment-emergent Adverse Event (TEAE). Treatment-related TEAE were determined by investigators.
Number of Participants With Laboratory Abnormalities During Treatment Period Baseline up to Week 24 Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology(Hemoglobin, Hematocrit, RBC count, Reticulocyte count, Platelet count, WBC count with differential, Total neutrophils, Eosinophils, Monocytes, Basophils, Lymphocytes); serum chemistry (BUN and Creatinine, Cystatin C, Creatine Phosphokinase, Glucose , Na+, K+, Cl ,Ca++, Total CO2, AST, ALT, Total Indirect \& Direct Bilirubin, Alkaline phosphatase, Uric acid, Albumin,Total protein, Fasting lipid Profile Panel; urinalysis(pH, Glucose, Protein, Nitrites, Leukocyte esterase, Microscopy culture);Other(HIV, HBsAg, HBcAb, HepB reflex (HbsAB), if applicable, HCVAb, Serum pregnancy test, Urine pregnancy test, FSH, QFT G or other IGRA, or PPD, EBV, CMV, HSV1, HSV2, VZV, Skin swab for herpetiform rash, Skin swab for potential drug related rash).Retest/discontinuation criteria are defined in Protocol Appendix 6.1 and 6.2 respectively.
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) Week 24 up to Week 52 Time to re-treatment (weeks) = (date of re-treatment criteria met - date at Week 24 +1)/7. The calendar time to retreatment was calculated. Baseline is defined as Week 24 measurement. The duration in Drug Holiday #1 (ranging from 2-6 weeks) is counted in the Kaplan-Meier analysis. One subject directly entered the re-treatment period and hence is censored at baseline in the Kaplan-Meier analysis.
Change From Baseline in SALT Across Time (SBE Period) 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) SALT is a quantitative assessment of alopecia areata (AA) severity based on the scalp hair loss. The SALT score can vary from 0 to 100% with higher score indicates more severe disease. Baseline is defined as the last measurement prior to first dosing (Day 1). Change from baseline is defined as the baseline value minus the value at a specific visit. Positive change from baseline implies an improvement. Least Square Mean and 90% confidence interval in this outcome measurement is the LSM and 90%CI for difference from initial 24-week treatment period placebo respectively.
Percentage of Participants Achieving SALT 30 Across Time (SBE Period) 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) SALT is a quantitative assessment of alopecia areata (AA) severity based on the scalp hair loss. A SALT 30 response is a 30% or greater reduction from baseline in SALT score. The SALT score can vary from 0 to 100%, with higher scores representing increasing severity of disease. The analysis was done using FAS (full analysis set) based on Non-responder imputation (ie. set missing values to be non-responsive) data. The percentage(Number) and 90% confidence interval (CI) in this outcome measurement is the percentage and 90% CI for difference from initial 24-week treatment period placebo. The 90% CI was calculated using Chan and Zhang method.
Percentage of Participants Achieving SALT 50 Across Time (SBE Period) 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) SALT is a quantitative assessment of alopecia areata (AA) severity based on the scalp hair loss. A SALT 50 response is a 50% or greater reduction from baseline in SALT score. The SALT score can vary from 0 to 100%, with higher scores representing increasing severity of disease. The analysis was done using FAS (full analysis set) based on Non-responder imputation (ie. set missing values to be non-responsive) data. The percentage(Number) and 90% confidence interval (CI) in this outcome measurement is the percentage and 90% CI for difference from initial 24-week treatment period placebo. The 90% CI was calculated using Chan and Zhang method.
Percentage of Participants Achieving SALT 75 Across Time (SBE Period) 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) SALT is a quantitative assessment of alopecia areata (AA) severity based on the scalp hair loss. A SALT 75 response is a 75% or greater reduction from baseline in SALT score. The SALT score can vary from 0 to 100%, with higher scores representing increasing severity of disease. The analysis was done using FAS (full analysis set) based on Non-responder imputation (ie. set missing values to be non-responsive) data. The percentage(Number) and 90% confidence interval (CI) in this outcome measurement is the percentage and 90% CI for difference from initial 24-week treatment period placebo. The 90% CI was calculated using Chan and Zhang method.
Percentage of Participants Achieving SALT 90 Across Time (SBE Period) 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) SALT is a quantitative assessment of alopecia areata (AA) severity based on the scalp hair loss. A SALT 90 response is a 90% or greater reduction from baseline in SALT score. The SALT score can vary from 0 to 100%, with higher scores representing increasing severity of disease. The analysis was done using FAS (full analysis set) based on Non-responder imputation (ie. set missing values to be non-responsive) data. The percentage(Number) and 90% confidence interval (CI) in this outcome measurement is the percentage and 90% CI for difference from initial 24-week treatment period placebo. The 90% CI was calculated using Chan and Zhang method.
Percentage of Participants Achieving SALT 100 Across Time (SBE Period) 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) SALT is a quantitative assessment of alopecia areata (AA) severity based on the scalp hair loss. A SALT 100 response is a 100% or greater reduction from baseline in SALT score. The SALT score can vary from 0 to 100%, with higher scores representing increasing severity of disease. The analysis was done using FAS (full analysis set) based on Non-responder imputation (ie. set missing values to be non-responsive) data. The percentage(Number) and 90% confidence interval (CI) in this outcome measurement is the percentage and 90% CI for difference from initial 24-week treatment period placebo. The 90% CI was calculated using Chan and Zhang method.
Trial Locations
- Locations (55)
Yale Hearing and Balance Center
🇺🇸New Haven, Connecticut, United States
Yale School of Medicine
🇺🇸New Haven, Connecticut, United States
Yale New Haven Hospital
🇺🇸New Haven, Connecticut, United States
Park Avenue Dermatology
🇺🇸Orange Park, Florida, United States
Edward B. Kampsen, MD
🇺🇸Tampa, Florida, United States
Park Avenue Dermatology Administrative Annex
🇺🇸Orange Park, Florida, United States
Rose Radiology
🇺🇸Tampa, Florida, United States
Forward Clinical Trials, Inc
🇺🇸Tampa, Florida, United States
Health Concepts
🇺🇸Rapid City, South Dakota, United States
University of Utah MidValley Dermatology
🇺🇸Murray, Utah, United States
University of Utah Medical Center
🇺🇸Salt Lake City, Utah, United States
The Skin Centre
🇦🇺Benowa, Queensland, Australia
Sinclair Dermatology
🇦🇺East Melbourne, Victoria, Australia
Bridge Road Imag ing
🇦🇺Richmond, Victoria, Australia
Research by ICLS
🇨🇦Oakville, Ontario, Canada
The Centre for Dermatology
🇨🇦Richmond Hill, Ontario, Canada
Veracity Clinical Research
🇦🇺Woolloongabba, Queensland, Australia
SKiN Centre for Dermatology
🇨🇦Peterborough, Ontario, Canada
NorthShore University HealthSystem Dermatology Clinical Trials Unit
🇺🇸Skokie, Illinois, United States
Massachusetts General Hospital Clinical Unit for Research Trials in Skin (CURTIS)
🇺🇸Boston, Massachusetts, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
University of Alabama at Birmingham, Dermatology at the Whitaker Clinic
🇺🇸Birmingham, Alabama, United States
Southern California Dermatology, Inc.
🇺🇸Santa Ana, California, United States
University of Alabama at Birmingham, The Kirklin Clinic
🇺🇸Birmingham, Alabama, United States
Tower Saint John's Imaging
🇺🇸Santa Monica, California, United States
Office of F. Monte Purcelli
🇺🇸Santa Monica, California, United States
Investigational Drug Services
🇺🇸New Haven, Connecticut, United States
Church Street Research Unit
🇺🇸New Haven, Connecticut, United States
Olympian Clinical Research
🇺🇸Tampa, Florida, United States
MedaPhase Inc.
🇺🇸Newnan, Georgia, United States
Dawes Fretzin Dermatology Group, LLC
🇺🇸Indianapolis, Indiana, United States
Dawes Fretzin Clinical Research Group, LLC
🇺🇸Indianapolis, Indiana, United States
University of Rochester Radiology
🇺🇸Rochester, New York, United States
Dr. Glen and Partners Medical Imaging
🇦🇺Kogarah, New South Wales, Australia
Hearing Life
🇦🇺Hurstville, New South Wales, Australia
St. George Hearing and Balance Clinic
🇦🇺Kogarah, New South Wales, Australia
Skin & Cancer Foundation Inc.
🇦🇺Carlton, Victoria, Australia
Richmond Audiology
🇦🇺Richmond, Victoria, Australia
Lynderm Research Inc.
🇨🇦Markham, Ontario, Canada
York Dermatology Center
🇨🇦Richmond Hill, Ontario, Canada
Weill Cornell Medicine
🇺🇸New York, New York, United States
Mount Sinai Department of Otolaryngology
🇺🇸New York, New York, United States
Rockefeller University Hospital
🇺🇸New York, New York, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Clinical Science Institute
🇺🇸Santa Monica, California, United States
Investigational Drug Service
🇺🇸Rochester, New York, United States
University of Rochester Audiology
🇺🇸Rochester, New York, United States
Virginia Clinical Research, Inc.
🇺🇸Norfolk, Virginia, United States
Vital Prospects Clinical Research Institute, P.C.
🇺🇸Tulsa, Oklahoma, United States
University of Colorado Hospital, Anschutz Cancer Pavilion
🇺🇸Aurora, Colorado, United States
University of Colorado Hospital Clinical and Translational Research Center, Inpatient Unit
🇺🇸Aurora, Colorado, United States
University of Colorado Hospital Clinical and Translational Research Center, Outpatient Clinic
🇺🇸Aurora, Colorado, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Wiseman Dermatology Research Inc.
🇨🇦Winnipeg, Manitoba, Canada
St George Dermatology and Skin Cancer Centre
🇦🇺Kogarah, New South Wales, Australia