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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
269
10 mg of PF-04965842 QD for 12 weeks
30 mg of PF-04965842 QD for 12 weeks
100 mg of PF-04965842 QD for 12 weeks
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
The IGA score quantifies the severity of participants' atopic dermatitis (AD). Scores range from 0 to 4 and correspond to a category (clear, almost clear, mild, moderate and severe, respectively).
Time frame: Baseline and Week 12
Percent Change From Baseline in the Eczema Area and Severity Index (EASI) at Week 12
The EASI quantifies the severity of participants' AD based on both severity of lesion clinical signs and the percent of body surface area (BSA) affected. EASI is a composite scoring by the AD clinical evaluator of the degree of erythema, induration/population, excoriation, and lichenification (each scored separately) for each of 4 regions, with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The EASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of AD.
Time frame: Baseline and Week 12
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
The IGA score quantifies the severity of participants' AD. Scores range from 0 to 4 and correspond to a category (clear, almost clear, mild, moderate and severe, respectively).
Time frame: Baseline and all scheduled time points except Week 12, including Weeks 1, 2, 4, 6, 8, 13, 14, 16.
Percentage of Participants Achieving >=2 Points Improvement in the IGA From Baseline at All Scheduled Time Points
The IGA score quantifies the severity of participants' AD. Scores range from 0 to 4 and correspond to a category (clear, almost clear, mild, moderate and severe, respectively).
Time frame: Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 13, 14, 16
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200 mg of PF-04965842 QD for 12 weeks
Placebo QD for 12 weeks
Clinical Research Center of Alabama
Birmingham, Alabama, United States
California Dermatology & Clinical Research Institute
Encinitas, California, United States
Huntington Medical Foundation
Pasadena, California, United States
Peninsula Research Associates, Inc.
Rolling Hills Estates, California, United States
Emil A. Tanghetti MD dba Center for Dermatology and Laser Surgery
Sacramento, California, United States
TCR Medical Corporation
San Diego, California, United States
Clinical Science Institute
Santa Monica, California, United States
University of Connecticut Health Center (UConn Health)
Farmington, Connecticut, United States
Olympian Clinical Research
Clearwater, Florida, United States
North Florida Dermatology Associates, PA
Jacksonville, Florida, United States
...and 54 more locations
Percent Change From Baseline in the EASI Total Score at All Scheduled Time Points Except Week 12.
The EASI quantifies the severity of participants' AD based on both severity of lesion clinical signs and the percent of BSA affected. EASI is a composite scoring by the AD clinical evaluator of the degree of erythema, induration/population, excoriation, and lichenification (each scored separately) for each of 4 regions, with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The EASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of AD.
Time frame: Baseline and all scheduled time points except Week 12, including Weeks 1, 2, 4, 6, 8, 13, 14, 16
Percentage of Participants Achieving >=3 Points Improvement in the Pruritus Numerical Rating Scale (NRS) From Baseline at All Scheduled Time Points
The severity of itch (pruritus) due to AD was assessed using a horizontal NRS. Participants were asked to assess their "worst itching due to AD over the past 24 hours" on a NRS anchored by the terms "no itching" (0) and "worst possible itching" (10). The frequency of itch (pruritus) due to AD was assessed using a horizontal NRS. Participants were asked to assess their "frequency of itching due to AD over the past 24 hours" on a NRS anchored by the terms "never/no itching" (0) and "always/constant itching" (10).
Time frame: 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
Percentage of Participants Achieving >=4 Points Improvement in the Pruritus NRS From Baseline at All Scheduled Time Points
The severity of itch (pruritus) due to AD was assessed using a horizontal NRS. Participants were asked to assess their "worst itching due to AD over the past 24 hours" on a NRS anchored by the terms "no itching" (0) and "worst possible itching" (10). The frequency of itch (pruritus) due to AD was assessed using a horizontal NRS. Participants were asked to assess their "frequency of itching due to AD over the past 24 hours" on a NRS anchored by the terms "never/no itching" (0) and "always/constant itching" (10).
Time frame: 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
Time to Achieving >=3 Points Improvement in NRS
The severity of itch (pruritus) due to AD was assessed using a horizontal NRS. Participants were asked to assess their "worst itching due to AD over the past 24 hours" on a NRS anchored by the terms "no itching" (0) and "worst possible itching" (10). The frequency of itch (pruritus) due to AD was assessed using a horizontal NRS. Participants were asked to assess their "frequency of itching due to AD over the past 24 hours" on a NRS anchored by the terms "never/no itching" (0) and "always/constant itching" (10).
Time frame: Baseline till Week 16
Time to Achieving >=4 Points Improvement in NRS
The severity of itch (pruritus) due to AD was assessed using a horizontal NRS. Participants were asked to assess their "worst itching due to AD over the past 24 hours" on a NRS anchored by the terms "no itching" (0) and "worst possible itching" (10). The frequency of itch (pruritus) due to AD was assessed using a horizontal NRS. Participants were asked to assess their "frequency of itching due to AD over the past 24 hours" on a NRS anchored by the terms "never/no itching" (0) and "always/constant itching" (10).
Time frame: Baseline till Week 16
Percent Change From Baseline in the Pruritus NRS From Baseline at All Scheduled Time Points
The severity of itch (pruritus) due to AD was assessed using a horizontal NRS. Participants were asked to assess their "worst itching due to AD over the past 24 hours" on a NRS anchored by the terms "no itching" (0) and "worst possible itching" (10). The frequency of itch (pruritus) due to AD was assessed using a horizontal NRS. Participants were asked to assess their "frequency of itching due to AD over the past 24 hours" on a NRS anchored by the terms "never/no itching" (0) and "always/constant itching" (10).
Time frame: 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
Change From Baseline in Pruritus NRS Score at All Scheduled Time Points
The severity of itch (pruritus) due to AD was assessed using a horizontal NRS. Participants were asked to assess their "worst itching due to AD over the past 24 hours" on a NRS anchored by the terms "no itching" (0) and "worst possible itching" (10). The frequency of itch (pruritus) due to AD was assessed using a horizontal NRS. Participants were asked to assess their "frequency of itching due to AD over the past 24 hours" on a NRS anchored by the terms "never/no itching" (0) and "always/constant itching" (10).
Time frame: 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
Percentage of Participants Achieving a >=50% Improvement in the EASI Total Score (EASI50) at All Scheduled Time Points
The EASI quantifies the severity of participants' AD based on both severity of lesion clinical signs and the percent of BSA affected. EASI is a composite scoring by the AD clinical evaluator of the degree of erythema, induration/population, excoriation, and lichenification (each scored separately) for each of 4 regions, with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The EASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of AD.
Time frame: All scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 13, 14, 16
Percentage of Participants Achieving a >=75% Improvement in the EASI Total Score (EASI75) at All Scheduled Time Points
The EASI quantifies the severity of participants' AD based on both severity of lesion clinical signs and the percent of BSA affected. EASI is a composite scoring by the AD clinical evaluator of the degree of erythema, induration/population, excoriation, and lichenification (each scored separately) for each of 4 regions, with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The EASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of AD.
Time frame: All scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 13, 14, 16
Percentage of Participants Achieving a >=90% Improvement in the EASI Total Score (EASI90) at All Scheduled Time Points
The EASI quantifies the severity of participants' AD based on both severity of lesion clinical signs and the percent of BSA affected. EASI is a composite scoring by the AD clinical evaluator of the degree of erythema, induration/population, excoriation, and lichenification (each scored separately) for each of 4 regions, with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The EASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of AD.
Time frame: All scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 13, 14, 16
Change From Baseline in Affected BSA at All Scheduled Time Points
BSA Efficacy is derived from the sum of the BSA in handprints across 4 body regions assessed as part of the EASI assessment. Handprint refers to that of each individual participant for their own measurement. The BSA Efficacy ranges from 0 to 100%, with higher values representing greater severity of AD. Since the scalp, palms, and soles are excluded from the BSA (Efficacy) assessment, the maximum possible value is less than 100%.
Time frame: Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 13, 14, 16
Change From Baseline in Scoring Atopic Dermatitis (SCORAD) at All Scheduled Time Points
SCORAD is a validated scoring index for AD, which combines extent (0-100), severity (0-18), and subjective symptoms (0-20) based on pruritus and sleep loss, each scored (0-10). Extent, denoted as A, is measured by BSA affected by AD as a percentage of the whole BSA. The score for each body region is added up to determine A (maximum of 100%). Severity, denoted as B, consists of the severity of several signs. Each is assessed as none(0), mild(1), moderate(2) or severe(3). The severity scores are added together to give B (maximum of 18). Subjective symptoms, denoted as C, are each scored by the subject or caregiver using a numeric rating scale (NRS) where "0" is no itch (or no sleeplessness) and "10" is the worst imaginable itch (or sleeplessness). These scores are added to give 'C' (maximum of 20). The SCORAD for an individual is calculated by the formula: A/5 + 7B/2 + C (can range from 0 to 103). Higher values of SCORAD represent worse outcome.
Time frame: Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 13, 14, 16
Percent Change From Baseline in SCORAD at All Scheduled Time Points
SCORAD is a validated scoring index for AD, which combines extent (0-100), severity (0-18), and subjective symptoms (0-20) based on pruritus and sleep loss, each scored (0-10). Extent, denoted as A, is measured by BSA affected by AD as a percentage of the whole BSA. The score for each body region is added up to determine A (maximum of 100%). Severity, denoted as B, consists of the severity of several signs. Each is assessed as none(0), mild(1), moderate(2) or severe(3). The severity scores are added together to give B (maximum of 18). Subjective symptoms, denoted as C, are each scored by the subject or caregiver using a numeric rating scale (NRS) where "0" is no itch (or no sleeplessness) and "10" is the worst imaginable itch (or sleeplessness). These scores are added to give 'C' (maximum of 20). The SCORAD for an individual is calculated by the formula: A/5 + 7B/2 + C (can range from 0 to 103). Higher values of SCORAD represent worse outcome.
Time frame: Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 13, 14, 16
Percentage of Participants Achieving a >=50% Improvement in SCORAD (SCORAD50) From Baseline at All Scheduled Time Points
SCORAD is a validated scoring index for AD, which combines extent (0-100), severity (0-18), and subjective symptoms (0-20) based on pruritus and sleep loss, each scored (0-10). Extent, denoted as A, is measured by BSA affected by AD as a percentage of the whole BSA. The score for each body region is added up to determine A (maximum of 100%). Severity, denoted as B, consists of the severity of several signs. Each is assessed as none(0), mild(1), moderate(2) or severe(3). The severity scores are added together to give B (maximum of 18). Subjective symptoms, denoted as C, are each scored by the subject or caregiver using a numeric rating scale (NRS) where "0" is no itch (or no sleeplessness) and "10" is the worst imaginable itch (or sleeplessness). These scores are added to give 'C' (maximum of 20). The SCORAD for an individual is calculated by the formula: A/5 + 7B/2 + C (can range from 0 to 103). Higher values of SCORAD represent worse outcome.
Time frame: Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 13, 14, 16
Percentage of Participants Achieving a >=75% Improvement in SCORAD (SCORAD75) From Baseline at All Scheduled Time Points
SCORAD is a validated scoring index for AD, which combines extent (0-100), severity (0-18), and subjective symptoms (0-20) based on pruritus and sleep loss, each scored (0-10). Extent, denoted as A, is measured by BSA affected by AD as a percentage of the whole BSA. The score for each body region is added up to determine A (maximum of 100%). Severity, denoted as B, consists of the severity of several signs. Each is assessed as none(0), mild(1), moderate(2) or severe(3). The severity scores are added together to give B (maximum of 18). Subjective symptoms, denoted as C, are each scored by the subject or caregiver using a numeric rating scale (NRS) where "0" is no itch (or no sleeplessness) and "10" is the worst imaginable itch (or sleeplessness). These scores are added to give 'C' (maximum of 20). The SCORAD for an individual is calculated by the formula: A/5 + 7B/2 + C (can range from 0 to 103). Higher values of SCORAD represent worse outcome.
Time frame: Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 13, 14, 16
Number of Participants With Treatment-emergent Adverse Events (AEs)
An AE was any untoward medical occurrence in a subject administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. Treatment-emergent AEs were events that occurred between the first dose of study drug and the subject's last visit (Week 16) that were absent before treatment or that worsened relative to pretreatment state.
Time frame: Baseline till Week 16
Number of Participants With Specific Clinical Laboratory Abnormalities (Anemia, Neutropenia, Thrombocytopenia, Lymphopenia, Lipid Profile, Liver Function Tests (LFTs)
Time frame: Baseline up to Week 16
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
The PtGA asked the participant to evaluate the overall cutaneous disease at that point in time on a single-item, 5-point scale. The same category labels used in the Physician's Global Assessment was used for the PtGA, ie, "severe (4)", "moderate (3)", "mild (2)","almost clear (1)", and "clear (0)". The PtGA was completed as per schedule of activities.
Time frame: Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 14, 16
Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at All Scheduled Time Points
The DLQI is a general dermatology questionnaire that consists of 10 items that assess participant health-related quality of life (daily activities, personal relationships, symptoms and feelings, leisure, work and school, and treatment). It has been extensively used in clinical trials for AD. The DLQI is a psychometrically valid and reliable instrument that has been translated into several languages, and the DLQI total scores have been shown to be responsive to change. The minimally important difference for the DLQI has been estimated as a 2-5 point change from baseline. Each item is scored as "very much (3)", "a lot (2)", "a little (1)" and "not at all (0)". The score can range from 0 to 30. The higher values represent the worse dermatology life quality.
Time frame: Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 14, 16
Change From Baseline in Patient Oriented Eczema Measure (POEM) at All Scheduled Time Points
The POEM is a 7-item patient reported outcome (PRO) measure used to assess the impact of AD over the past week. Each item is scored as "no days (0)", "1-2 days (1)", "3-4 days (2)", "5-6 days (3)" and "every day (4)". The score ranges from 0 to 28. The higher values represent more severe AD.
Time frame: Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 14, 16
Change From Baseline in the Hospital and Anxiety Depression Scale (HADS) at All Scheduled Time Points
The HADS is a 14-item PRO measure used to detect states of anxiety and depression over the past week. The HADS was completed as per schedule of activities. Seven of the items relate to anxiety and seven relate to depression. Each item is scored from 0 to 3 which means a person can score between 0 to 21 for either anxiety or depression. Higher values represent worse outcome.
Time frame: Baseline and all scheduled time points, including Weeks 1, 2, 4, 6, 8, 12, 14, 16