JAK1 Inhibitor With Medicated Topical Therapy in Adolescents With Atopic Dermatitis (JADE TEEN)

• ClinicalTrials.gov Identifier: NCT03796676
• Recruitment Status: Completed
• First Posted: January 8, 2019
• Results First Posted: June 4, 2021
• Last Update Posted: April 13, 2022
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: January 4, 2019
• First Posted Date: January 8, 2019
• Results First Submitted Date: March 18, 2021
• Results First Posted Date: June 4, 2021
• Last Update Posted Date: April 13, 2022
• Actual Study Start Date: February 18, 2019
• Actual Primary Completion Date: April 8, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 10, 2021)

• Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of 'Clear' (0) or 'Almost Clear' (1) and ≥2 Points Improvement From Baseline at Week 12 [ Time Frame: Baseline to Week 12 ]
  The IGA of Atopic Dermatitis (AD) was scored on a 5-point scale (0-4), reflecting a global consideration of the erythema, induration and scaling. The overall severity of AD was assessed according to the 5-point scale: 0=Clear, 1=Almost Clear, 2=Mild, 3=Moderate, and 4=Severe. Participants who withdrew from the study were counted as non-responder.
• Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Response ≥ 75% Improvement From Baseline at Week 12 [ Time Frame: Baseline to Week 12 ]
  The EASI quantifies the severity of AD based on both severity of lesion clinical signs and the percent of body surface area (BSA) affected. 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. Participants who withdrew from the study were counted as non-responder.

Original Primary Outcome Measures (submitted: January 4, 2019)

• Change from baseline response based on IGA score of 0 or 1 and a reduction from baseline of at least 2 points. [ Time Frame: Day 1 (Baseline), Week 12 (end of treatment/early termination). ]
  Investigator's Global Assessment (IGA) assessed the severity of AD (except scalp, palms and soles) on a 5-point scale ranged from 0 (clear) to 4 (severe), where higher scores indicate higher degree of AD. Grades for classification of severity: 0= clear (AD is cleared, except for any residual discoloration, post-inflammatory hyperpigmentation and/or hypopigmentation), 1= almost clear, 2= mild , 3= moderate and 4= severe. Percentage of participants with an ISGA score of 0 or 1 were reported.
• Change from baseline response based on the Eczema Area and Severity Index of more than 75% improvement from baseline (EASI-75). [ Time Frame: Day 1 (Baseline), Week 12 (end of treatment/early termination). ]
  The Eczema Area and Severity Index (EASI) quantifies the severity of a subject's AD based on both severity of lesion clinical signs and the percent of body surface area (BSA) affected. EASI is a composite scoring of the degree of erythema, induration/papulation, excoriation, and lichenification (each scored separately) for each of four body 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.

Current Secondary Outcome Measures (submitted: May 10, 2021)

• Percentage of Participants Achieving ≥4 Points Improvement From Baseline in Peak Pruritis Numeric Rating Scale (PP-NRS) for Severity of Pruritus at Weeks 2, 4 and 12 [ Time Frame: Baseline, Weeks 2, 4 and 12 ]
  PP-NRS assesses the severity of itch (pruritus) due to AD. Participants were asked to assess their worst itching due to AD on an NRS anchored by the terms "no itch" (0) and "worst itch imaginable" (10). Participants who withdrew from the study were counted as non-responder.
• Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) at Week 12 [ Time Frame: Baseline to Week 12 ]
  The PSAAD is a daily patient reported symptom diary presented as a 15 item questionnaire that includes 11 items developed to measure symptoms of AD, along with 4 additional items for exploratory and psychometric validation purposes (Sleep & Usual Activities Questions and Patient Global Impression of Severity & Patient Global Impression of Change Questions). Participants answer each question about skin condition based on a 24 hour recall. Each question was evaluated on a 11-point scale ranging from 0 to 10, where higher scores indicate more impact on skin condition.The PSAAD total score is calculated as the average of the responses to each of the 11 items and ranges from 0 (none) to 10 (extreme), where higher scores indicate worse severity of AD symptoms.
• Percentage of Participants Achieving IGA Response of 'Clear' or 'Almost Clear' and ≥2 Points Improvement From Baseline at All Scheduled Time Points Except Week 12 [ Time Frame: Baseline, Weeks 2, 4 and 8 ]
  The IGA of AD is scored on a 5-point scale (0-4), reflecting a global consideration of the erythema, induration and scaling. The overall severity of AD was assessed according to the 5-point scale: 0=Clear, 1=Almost Clear, 2=Mild, 3=Moderate, and 4=Severe. Participants who withdrew from the study were counted as non-responder.
• Percentage of Participants Achieving EASI Response ≥ 75% Improvement From Baseline at All Scheduled Time Points Except Week 12 [ Time Frame: Baseline, Weeks 2, 4 and 8 ]
  The EASI quantifies the severity of AD based on both severity of lesion clinical signs and the percent of BSA affected. 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. Participants who withdrew from the study were counted as non-responder.
• Percentage of Participants Achieving EASI Response ≥ 50% Improvement From Baseline [ Time Frame: Baseline, Weeks 2, 4, 8 and 12 ]
  The EASI quantifies the severity of AD based on both severity of lesion clinical signs and the percent of BSA affected. 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. Participants who withdrew from the study were counted as non-responder.
• Percentage of Participants Achieving EASI Response ≥ 90% Improvement From Baseline [ Time Frame: Baseline, Weeks 2, 4, 8 and 12 ]
  The EASI quantifies the severity of AD based on both severity of lesion clinical signs and the percent of BSA affected. 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. Participants who withdrew from the study were counted as non-responder.
• Percentage of Participants Achieving EASI Response =100% Improvement From Baseline [ Time Frame: Baseline, Weeks 2, 4, 8 and 12 ]
  The EASI quantifies the severity of AD based on both severity of lesion clinical signs and the percent of BSA affected. 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. Participants who withdrew from the study were counted as non-responder.
• Percent Change From Baseline in EASI Score [ Time Frame: Baseline, Weeks 2, 4, 8 and 12 ]
  The EASI quantifies the severity of AD based on both severity of lesion clinical signs and the percent of BSA affected. 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. Participants who withdrew from the study were counted as non-responder.
• Percentage of Participants Achieving ≥4 Points Improvement From Baseline in PP-NRS for Severity of Pruritus at All Scheduled Time Points Other Than Weeks 2, 4 and 12 [ Time Frame: Baseline, Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15 ]
  PP-NRS assesses the severity of itch (pruritus) due to AD. Participants were asked to assess their worst itching due to AD on an NRS anchored by the terms "no itch" (0) and "worst itch imaginable" (10). Participants who withdrew from the study were counted as non-responder.
• Time to First Achieve ≥4 Points Improvement From Baseline in PP-NRS for Severity of Pruritus [ Time Frame: Baseline to Week 16 ]
  PP-NRS assesses the severity of itch (pruritus) due to AD. Participants were asked to assess their worst itching due to AD on an NRS anchored by the terms "no itch" (0) and "worst itch imaginable" (10).
• Percent Change From Baseline in PP-NRS for Severity of Pruritus [ Time Frame: Baseline, Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 ]
  PP-NRS assesses the severity of itch (pruritus) due to AD. Participants were asked to assess their worst itching due to AD on an NRS anchored by the terms "no itch" (0) and "worst itch imaginable" (10).
• Change From Baseline in Percentage Body Surface Area (BSA) [ Time Frame: Baseline, Weeks 2, 4, 8 and 12 ]
  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. The percentage BSA ranges from 0 to 100, with higher scores representing greater severity of AD. Since the scalp, palms, and soles were excluded from the BSA (efficacy) assessment, the maximum possible percentage BSA was less than 100.
• Percent Change From Baseline in Percentage BSA [ Time Frame: Baseline, Weeks 2, 4, 8 and 12 ]
  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. The percentage BSA ranges from 0 to 100, with higher scores representing greater severity of AD. Since the scalp, palms, and soles were excluded from the BSA (efficacy) assessment, the maximum possible percentage BSA was less than 100.
• Percentage of Participants Achieving Percentage BSA < 5% at Week 12 [ Time Frame: Baseline to Week 12 ]
  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. The percentage BSA ranges from 0 to 100, with higher scores representing greater severity of AD. Since the scalp, palms, and soles were excluded from the BSA (efficacy) assessment, the maximum possible percentage BSA was less than 100.
• Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response ≥ 50% Improvement From Baseline [ Time Frame: Baseline, Weeks 2, 4, 8 and 12 ]
  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 participant using a 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).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.
• Percentage of Participants Achieving SCORAD Response ≥ 75% Improvement From Baseline [ Time Frame: Baseline, Weeks 2, 4, 8 and 12 ]
  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 participant using a 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).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.
• Change From Baseline in SCORAD Total Score [ Time Frame: Baseline, Weeks 2, 4, 8 and 12 ]
  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 participant using a 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).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.
• Percent Change From Baseline in SCORAD Total Score [ Time Frame: Baseline, Weeks 2, 4, 8 and 12 ]
  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 participant using a 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).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.
• Change From Baseline in SCORAD Subjective Visual Analogue Scale (VAS) of Sleep Loss [ Time Frame: Baseline, Weeks 2, 4, 8 and 12 ]
  SCORAD is a validated scoring index for AD, which combines extent (A, 0-100), severity (B, 0-18), and subjective symptoms (C, 0-20) based on pruritus and sleep loss, each scored (0-10). The SCORAD for an individual is calculated by the formula: A/5 + 7B/2 + C (can range from 0 to 103). Subjective symptoms (ie, itch and sleep loss) are each scored by the participant using a VAS where "0" is no itch (or no sleep loss) and "10" is the worst imaginable itch (or sleep loss). The value for each should reflect the average on a 10 point scale for the last 3 days/nights. Changes from baseline in SCORAD subjective assessments of itch were not evaluated. Only changes from baseline in SCORAD subjective assessments of sleep loss are presented below.
• Percent Change From Baseline in SCORAD Subjective VAS of Sleep Loss [ Time Frame: Baseline, Weeks 2, 4, 8 and 12 ]
  SCORAD is a validated scoring index for AD, which combines extent (A, 0-100), severity (B, 0-18), and subjective symptoms (C, 0-20) based on pruritus and sleep loss, each scored (0-10). The SCORAD for an individual is calculated by the formula: A/5 + 7B/2 + C (can range from 0 to 103). Subjective symptoms (ie, itch and sleep loss) are each scored by the participant using a VAS where "0" is no itch (or no sleep loss) and "10" is the worst imaginable itch (or sleep loss). The value for each should reflect the average on a 10 point scale for the last 3 days/nights. Changes from baseline in SCORAD subjective assessments of itch were not evaluated. Only changes from baseline in SCORAD subjective assessments of sleep loss are presented below.
• Number of Days When a Corticosteroid Not Used up to Day 88 [ Time Frame: Baseline to Day 88 ]
• Change From Baseline in Children's Dermatology Life Quality Index (DLQI) [ Time Frame: Baseline, Weeks 2, 4, 8 and 12 ]
  The DLQI is a general dermatology questionnaire that consists of 10 items to assess participant-reported health-related quality of life (daily activities, personal relationships, symptoms and feelings, leisure, work and school, and treatment).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 3-5 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. Participants who withdrew from the study were counted as non-responder.
• Percentage of Participants With ≥2.5 Points at Baseline and Achieving ≥2.5 Points Improvement From Baseline in Children's DLQI [ Time Frame: Baseline, Weeks 2, 4, 8 and 12 ]
  The DLQI is a general dermatology questionnaire that consists of 10 items to assess participant-reported health-related quality of life (daily activities, personal relationships, symptoms and feelings, leisure, work and school, and treatment).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 3-5 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. Participants who withdrew from the study were counted as non-responder.
• Change From Baseline in Anxiety of Hospital Anxiety and Depression Scale (HADS) [ Time Frame: Baseline, Weeks 2, 4, 8 and 12 ]
  The HADS is a 14-item patient reported outcome (PRO) measure used to detect states of anxiety and depression over the past week. 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.
• Change From Baseline in Depression of HADS [ Time Frame: Baseline, Weeks 2, 4, 8 and 12 ]
  The HADS is a 14-item patient reported outcome (PRO) measure used to detect states of anxiety and depression over the past week. 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.
• Change From Baseline in Patient-Oriented Eczema Measure (POEM) [ Time Frame: Baseline, Weeks 2, 4, 8 and 12 ]
  The POEM is a 7-item 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.
• Change From Baseline in Dermatitis Family Impact (DFI) at Week 12 [ Time Frame: Baseline to Week 12 ]
  The DFI is a validated 10-item measure filled out by the parent/caregiver of the patient used to assess the impact of the patient's eczema on the family. The instrument has a recall period of 7 days. Each item is scored as "very much (3)", "a lot (2)", "a little (1)" or "not at all (0)". The score can range from 0 to 30. The higher values represent the worse impact.
• Change From Baseline in Patient Global Assessment (PtGA) [ Time Frame: Baseline, Weeks 2, 4, 8 and 12 ]
  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 IGA were 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.
• Percentage of Participants With ≥2 Points at Baseline and Achieving 'Clear' or 'Almost Clear' and ≥2 Points Improvement From Baseline in PtGA [ Time Frame: Baseline, Weeks 2, 4, 8 and 12 ]
  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 IGA were 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.
• Change From Baseline in EuroQol Quality of Life 5-Dimension Youth Scale (EQ-5D-Y) VAS Score [ Time Frame: Baseline, Weeks 2, 4, 8 and 12 ]
  The EQ-5D is a validated, standardized, generic instrument that is the most widely used preference based health related quality of life questionnaire in cost effectiveness and health technologies assessment. The EQ-5D-Y is a version of the instrument specifically developed and validated for use by youths aged 12 through 17 years. Components assess level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety and depression. Score scale for each domain ranges from 1 (minimum) to 3 (maximum), with higher scores indicating worse health condition. In addition, respondents use a vertical, graduated Visual Analogue Scale (VAS) to rate their own health between 0 (the worst) and 100 (the best health state he/she can imagine).
• Change From Baseline in Pediatric Functional Assessment of Chronic Illness Therapy Fatigue Scale (Peds-FACIT-F) at Week 12 [ Time Frame: Baseline to Week 12 ]
  The Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F) is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (none of the time) to 4 (all of the time). Larger the participant's response to the questions (with the exception of 2 negatively stated), greater was the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-F score for a total possible score of 0 (worse score) to 52 (better score), with higher scores representing better overall health status (less fatigue). Changes from baseline at Week 12 are presented below. Changes from baseline at other scheduled time points were not evaluated.
• Number of Participants With Treatment Emergent Adverse Events (TEAEs) [ Time Frame: 16 weeks ]
  An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. TEAEs were AEs that occurred following the start of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator.
• Number of Participants With Serious Adverse Events (SAEs) [ Time Frame: 16 weeks ]
  A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Treatment-related SAEs were determined by the investigator.
• Number of Participants Who Discontinued From the Study Due to TEAEs [ Time Frame: 16 weeks ]
  An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. TEAEs were AEs that occurred following the start of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator.
• Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) [ Time Frame: 16 weeks ]
  Laboratory tests included hematology (including coagulation panel), clinical chemistry, lipid profile panel, and routine urinalysis. LLN is lower limit of normal. ULN is upper limit of normal.
• Number of Participants With Electrocardiogram (ECG) Data Meeting Prespecified Criteria [ Time Frame: 16 weeks ]
  A 12-lead ECG was obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT intervals. All scheduled ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position. Reading of ECGs were performed by a central reader who has expertise reading and interpreting ECGs in adolescents. The QTcF interval is the only prespecified ECG criteria (Marked prolongation of the QTcF interval to >500 ms or >60 ms change from screening ECG); data are presented below.
• Categorization of Vital Signs Data Meeting Prespecified Criteria [ Time Frame: 16 weeks ]
  Vital signs (pulse rate, systolic and diastolic blood pressure) were obtained with participant in the seated position, after having sat calmly for at least 5 minutes.
• Fold Increase of Immunoglobulin G (IgG) Concentrations Against Specific Vaccine Antigens at 4 Weeks Post-Vaccination [ Time Frame: 4 weeks post-vaccination with Tdap (Week 12) ]
  The immunogenicity analysis was to evaluate the effect of abrocitinib on immunogenicity to a tetanus, diphtheria and pertussis combination vaccine (Tdap) vaccine in adolescent participants 12 to <18 years of age with moderate to severe AD. Participants who completed 8 weeks of treatment with study intervention received Tdap at Week 8, and had blood samples collected for the evaluation of immunogenicity to the vaccine at Weeks 8 and 12. The fold increase was defined as the ratio (post-vaccination: pre-vaccination) of concentration values. The geometric mean fold rise (GMFR) is presented below, and was calculated by first arithmetically averaging the logarithmically transformed ratio (post-vaccination: pre-vaccination) values, and then back transformation. A 95% CI for GMFR was constructed by back transformation of the CI for the logarithmically transformed GMFRs computed using the Student's t distribution.
• Plasma PF-04965842 Concentration at Week 8 [ Time Frame: 2 hours pre-dose at Week 8 ]
• Plasma PF-04965842 Concentration at Week 12 [ Time Frame: 2 hours post-dose at Week 12 ]

Original Secondary Outcome Measures (submitted: January 4, 2019)

• Change from baseline response based on at least 4 points improvement in the Peak Pruritus NRS [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 12 (end of treatment/early termination). ]
  Participant-rated pruritus score of lesions rated the severity of pruritus suffered in the past 24 hours on an 11-point Numeric Rating Score (NRS) where 0 is no pruritus and 10 is most severe possible pruritus. Change: score at observation minus score at baseline.
• Change from baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) total score [ Time Frame: Day 1 (Baseline), Week 12 (end of treatment/early termination). ]
  The PSAAD is a daily patient reported symptom diary. The version is a 15 item questionnaire that includes 11 items developed to measure symptoms of AD, capturing those identified by patients to be most important, based on a 24 hour recall. Analysis of the PSAAD will be based solely on these 11 items.
• Change from baseline response based on at least 4 points improvement in the Peak Pruritus NRS [ Time Frame: Day 1 (Baseline), Days 2-14, Week 8, Week 16 (end of study). ]
  Participant-rated pruritus score of lesions rated the severity of pruritus suffered in the past 24 hours on an 11-point Numeric Rating Score (NRS) where 0 is no pruritus and 10 is most severe possible pruritus. Change: score at observation minus score at baseline.
• Time to achieve at least 4 points improvement in the Peak Pruritus NRS from baseline [ Time Frame: Day 1 (Baseline), Days 2-14, Day 15 (week 2) ]
  Participant-rated pruritus score of lesions rated the severity of pruritus suffered in the past 24 hours on an 11-point Numeric Rating Score (NRS) where 0 is no pruritus and 10 is most severe possible pruritus. Change: score at observation minus score at baseline.
• Change from baseline response based on the Eczema Area and Severity Index of more than 75% improvement from baseline (EASI-75). [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 16 (end of study). ]
  The Eczema Area and Severity Index (EASI) quantifies the severity of a subject's AD based on both severity of lesion clinical signs and the percent of body surface area (BSA) affected. EASI is a composite scoring of the degree of erythema, induration/papulation, excoriation, and lichenification (each scored separately) for each of four body 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.
• Change from baseline response based on Investigator's Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) and a reduction from baseline of at least 2 points. [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 16 (end of study). ]
  Investigator's Global Assessment (IGA) assessed the severity of AD (except scalp, palms and soles) on a 5-point scale ranged from 0 (clear) to 4 (severe), where higher scores indicate higher degree of AD. Grades for classification of severity: 0= clear (AD is cleared, except for any residual discoloration, post-inflammatory hyperpigmentation and/or hypopigmentation), 1= almost clear, 2= mild , 3= moderate and 4= severe. Percentage of participants with an ISGA score of 0 or 1 were reported.
• Change from baseline response based on the Eczema Area and Severity Index of more than 50% improvement from baseline (EASI-50). [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 12 (end of treatment/early termination), Week 16 (end of study). ]
  The Eczema Area and Severity Index (EASI) quantifies the severity of a subject's AD based on both severity of lesion clinical signs and the percent of body surface area (BSA) affected. EASI is a composite scoring of the degree of erythema, induration/papulation, excoriation, and lichenification (each scored separately) for each of four body 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.
• Change from baseline response based on the Eczema Area and Severity Index of more than 90% improvement from baseline (EASI-90). [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 12 (end of treatment/early termination), Week 16 (end of study). ]
  The Eczema Area and Severity Index (EASI) quantifies the severity of a subject's AD based on both severity of lesion clinical signs and the percent of body surface area (BSA) affected. EASI is a composite scoring of the degree of erythema, induration/papulation, excoriation, and lichenification (each scored separately) for each of four body 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.
• Change from baseline response based on the Eczema Area and Severity Index of 100% improvement from baseline (EASI-100). [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 12 (end of treatment/early termination), Week 16 (end of study). ]
  The Eczema Area and Severity Index (EASI) quantifies the severity of a subject's AD based on both severity of lesion clinical signs and the percent of body surface area (BSA) affected. EASI is a composite scoring of the degree of erythema, induration/papulation, excoriation, and lichenification (each scored separately) for each of four body 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.
• Change from baseline in the percentage Body Surface Area (%BSA) [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 12 (end of treatment/early termination), Week 16 (end of study). ]
  The number of handprints of AD skin in a body region can be used to determine the extent (%) to which a body region is involved with atopic dermatitis. The area represented by the palmar surface of the subject's hand with all five digits adducted together, is approximately 1% of the subject's BSA, regardless of the subject's age. BSA in handprints across 4 body regions assessed as part of the EASI assessment.
• Proportion of participants with affected BSA <5% [ Time Frame: Day 1 (Baseline), Week 12 (end of treatment/early termination). ]
  The number of handprints of AD skin in a body region can be used to determine the extent (%) to which a body region is involved with atopic dermatitis. The area represented by the palmar surface of the subject's hand with all five digits adducted together, is approximately 1% of the subject's BSA, regardless of the subject's age. BSA in handprints across 4 body regions assessed as part of the EASI assessment.
• Change from baseline response based on more than 50% improvement in Scoring Atopic Dermatitis (SCORAD50). [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 12 (end of treatment/early termination), Week 16 (end of study). ]
  SCORAD is a validated scoring index for AD, which combines A: extent (0-100), B: severity (0-18), and C: subjective symptoms (0-20) based on pruritus and sleep loss, each scored (0-10). The SCORAD for an individual is calculated by the formula: A/5 + 7B/2 + C (can range from 0 to 103).
• Change from baseline response based on more than 75% improvement in Scoring Atopic Dermatitis (SCORAD75). [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 12 (end of treatment/early termination), Week 16 (end of study). ]
  SCORAD is a validated scoring index for AD, which combines A: extent (0-100), B: severity (0-18), and C: subjective symptoms (0-20) based on pruritus and sleep loss, each scored (0-10). The SCORAD for an individual is calculated by the formula: A/5 + 7B/2 + C (can range from 0 to 103).
• Change from baseline in SCORAD subjective assessments of itch and sleep loss. [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 12 (end of treatment/early termination), Week 16 (end of study). ]
  SCORAD is a validated scoring index for AD, which combines A: extent (0-100), B: severity (0-18), and C: subjective symptoms (0-20) based on pruritus and sleep loss, each scored (0-10). The SCORAD for an individual is calculated by the formula: A/5 + 7B/2 + C (can range from 0 to 103). Only the subjective symptoms (0-20) based on pruritus and sleep loss, each scored (0-10), will be assessed.
• Change from baseline in Children's Dermatology Life Quality Index (CDLQI) [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 12 (end of treatment/early termination), Week 16 (end of study). ]
  The CDLQI is a 10-item questionnaire that measures the impact of skin disease on participant's quality of life. Each question is evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicate more impact on quality of life. The DLQI total score ranges from 0 (not at all) to 30 (very much): 0-1 = no effect at all on the participant's life; 2-6 = small effect on the participant's life; 7-12 = moderate effect on the participant's life; 13-18 = very large effect on the participant's life; 19-30 = extremely large effect on the participant's life. Higher scores indicate more impact on quality of life of participants.
• Change from baseline in the Hospital Anxiety and Depression Scale (HADS) [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 12 (end of treatment/early termination), Week 16 (end of study). ]
  HADS is a participant rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms.
• Change from baseline in Patient Oriented Eczema Measure (POEM) [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 12 (end of treatment/early termination), Week 16 (end of study). ]
  The POEM is a validated 7 item PRO measure used to assess the impact of AD recalled over the past week. It contains 7 symptom based questions with responses rating number of days each symptom was experienced over the past week, ranging from 0 (no days) to 4 (every day), with a maximum score of 28.
• Change from baseline in Dermatitis Family Impact (DFI) questionnaire [ Time Frame: Day 1 (Baseline), Week 12 (end of treatment/early termination). ]
  The DFI is a 10-item disease questionnaire that measures the impact of having a child with AD on family quality of life. It is completed by parent/legal guardian of the child (affected by AD), based on recall over the past week. Each question is scored on a 4-point scale ranging from 0 (good) to 3 (worst), where higher scores indicated worst quality of life of family. The DFI total score is the sum of individual scores of the 10 questions and ranges from 0 (good) to 30 (worst), where higher DFI scores indicated worst quality of life of family.
• Change from baseline of Patient Global Assessment (PtGA) [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 12 (end of treatment/early termination), Week 16 (end of study). ]
  The PtGA asks 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 Investigator's Global Assessment will be used for the Patient Global Assessment, ie, "severe (4)", "moderate (3)", "mild (2)", "almost clear (1)", and "clear (0)".
• Change from baseline of EuroQol Quality of Life 5 Dimension Youth Scale (EQ-5D-Y) [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 12 (end of treatment/early termination), Week 16 (end of study). ]
  The EQ-5D-Y is a validated, standardized, generic instrument that is the most widely used preference based health related quality of life questionnaire in cost effectiveness and health technologies assessment (HTA). The EQ-5D-Y is a version of the instrument specifically developed and validated for use by youths age 12 through 17 years. Components assessed level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety and depression. Score scale ranged from 1 (minimum) to 3 (maximum). Higher scores indicated worse health condition.
• Change from baseline of Pediatric Functional Assessment of Chronic Illness Therapy Fatigue Scale (Peds FACIT-F) [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 12 (end of treatment/early termination), Week 16 (end of study). ]
  FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (not at all) to 4 (very much). Larger the participant's response to the questions (with the exception of 2 negatively stated), greater was the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score).
• Incidence of treatment emergent adverse events [ Time Frame: From Screening through Week 16 (entire study) ]
  Incidence of treatment emergent AEs. An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. AEs are classified according to the severity in 3 categories a) mild (AEs does not interfere with participant's usual function); b) moderate (AEs interferes to some extent with participant's usual function) and c) severe (AEs interferes significantly with participant's usual function). AE's includes local tolerability, discontinuations and clinically significant changes in vital signs and clinical laboratory parameters. The investigator is to record all directly observed AE's and all AE's spontaneously reported by the subject (or subject's legal guardian). In addition, each study subject (or subject's legal guardian) will be questioned about the occurrence of AE's in a non-leading manner.
• Incidence of Serious Adverse Events (SAE's) [ Time Frame: From Screening through Week 16 (entire study) ]
  Incidence of SAEs, eg. an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
• Incidence of AEs leading to discontinuation; [ Time Frame: From Screening through Week 16 (entire study) ]
  Counts of participants who had adverse events leading to discontinuation.
• The incidence of clinical abnormalities and change from baseline in clinical laboratory values, ECG measurements, and vital signs. [ Time Frame: From Screening through Week 16 (entire study) ]
  Laboratory parameters included: hematology (hemoglobin, hematocrit, red blood cell, platelet and white blood cell count, neutrophils, eosinophils, monocytes, basophils and lymphocytes), chemistry (blood urea nitrogen, creatinine, sodium, potassium, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein and serum pregnancy test [for all female participants]) and urine (urine pregnancy test [for all female participants]). A 12-lead ECG was obtained after the participant had rested quietly for at least 10 minutes. Vital signs (pulse, systolic and diastolic blood pressure) were obtained with participant in the seated position, after having sat calmly for at least 5 minutes. Clinical significance was determined at the investigator's discretion.
• Mean fold increase from baseline in concentrations of immunoglobulin G (IgG) against tetanus, diphtheria, and acellular pertussis combination vaccine (Tdap) [ Time Frame: Week 8 (sub-study baseline), Week 12 (end of treatment). ]
  Mean fold increase will be assessed from baseline (week 8) at 4 weeks post-vaccination in concentrations of IgG against:

  • Tetanus toxoid;
  • Diphtheria toxoid;
  • Pertussis toxoid;
  • Pertactin (PRN);
  • Filamentous hemagglutinin (FHA);
  • Fimbriae types 2 and 3 (FIM).
• Plasma concentrations of PF 04965842 in adolescent participants 12 to <18 years of age with moderate to severe AD. [ Time Frame: Week 8, Week 12 (end of treatment). ]
  Plasma concentrations of PF-04965842 2 hours prior to dosing on Day 57 (week 8) and 2 hours post-dosing on Day 85 (Week 12)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: JAK1 Inhibitor With Medicated Topical Therapy in Adolescents With Atopic Dermatitis
• Official Title: A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTI-CENTER STUDY INVESTIGATING THE EFFICACY AND SAFETY OF PF-04965842 CO-ADMINISTERED WITH BACKGROUND MEDICATED TOPICAL THERAPY IN ADOLESCENT PARTICIPANTS 12 TO <18 YEARS OF AGE WITH MODERATE-TO-SEVERE ATOPIC DERMATITIS
• Brief Summary: This is a randomized, double blind, placebo controlled, parallel group, Phase 3 study to evaluate the efficacy and safety of PF 04965842 in adolescent participants 12 to <18 years of age with moderate to severe AD.

Detailed Description

This is a randomized, double blind, placebo controlled, parallel group, Phase 3 study to evaluate the efficacy and safety of PF 04965842 in adolescent participants 12 to <18 years of age with moderate to severe AD. Participants will be screened within 28 days prior to the first dose of study intervention to confirm study eligibility. Subjects must have moderate-severe AD involving at least 10% Body Surface Area (BSA); an Investigator Global Assessment (IGA) score of at least 3; an Eczema Area Severity Index (EASI) of at least 16 and Peak Pruritus Numerical Rating Score (NRS) of at least 4 on baseline/Day 1. Eligible subjects will be randomized at the Baseline/Day 1 visit. Approximately 225 participants will be randomized in a 1:1:1 ratio to receive once daily PF 04965842 at 200 mg, 100 mg, or placebo for 12 weeks. Randomization will be stratified by baseline disease severity (moderate [IGA = 3] vs. severe [IGA = 4] AD). The investigational products will be administered QD for 12 weeks. Background therapy (medicated and non-medicated topical therapy) must be applied BID for the duration of the treatment period. The co-primary efficacy endpoints are an IGA score of clear (0) or almost clear (1) with a reduction from baseline of greater than 2 points at Week 12 AND an at least 75% improvement of the EASI score (EASI-75) at week 12. Safety and efficacy assessments will be conducted at the investigator site by a clinical assessor blinded to treatment assignment. Scheduled clinic or telephone study visits for all subjects will occur at Screening, Baseline/Day 1, Day 8 (by phone), Day 15, Day 29, Day 43 (by phone), Day 57, Day 85 (End of treatment/Early termination), Day 113 (End of Study). Participants discontinuing early from the study will undergo a 4 week follow up period.

This study includes an immunogenicity sub study integrated into the last 4 weeks of the main study treatment period. At Week 8, up to approximately 90 participants (up to approximately 30 in each treatment arm) who have completed 8 weeks of treatment with study intervention will receive a tetanus, diphtheria and acellular pertussis combination vaccine (Tdap), and collection of blood samples for the evaluation of immunogenicity at Weeks 8 and 12. Participants of this sub study will complete all other protocol specified procedures in the main study.

At the end of the 12 week study treatment, qualified participants completing the study will have the option to enter the long term extension (LTE) study B7451015.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Atopic Dermatitis

Intervention

• Drug: Placebo
  Placebo
• Drug: PF-04965842
  100 mg QD
• Drug: PF04965842
  200 mg QD

Study Arms

• Placebo Comparator: Placebo
  Placebo
  Intervention: Drug: Placebo
• Experimental: PF-04965842 100 mg QD
  active
  Intervention: Drug: PF-04965842
• Experimental: PF-04965842 200 mg QD
  active
  Intervention: Drug: PF04965842

Publications *

• 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.
• Eichenfield LF, Flohr C, Sidbury R, Siegfried E, Szalai Z, Galus R, Yao Z, Takahashi H, Barbarot S, Feeney C, Zhang F, DiBonaventura M, Rojo R, Valdez H, Chan G. Efficacy and Safety of Abrocitinib in Combination With Topical Therapy in Adolescents With Moderate-to-Severe Atopic Dermatitis: The JADE TEEN Randomized Clinical Trial. JAMA Dermatol. 2021 Oct 1;157(10):1165-1173. doi: 10.1001/jamadermatol.2021.2830. Erratum In: JAMA Dermatol. 2021 Oct 1;157(10):1246.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 15, 2020): 287
• Original Estimated Enrollment (submitted: January 4, 2019): 225
• Actual Study Completion Date: April 8, 2020
• Actual Primary Completion Date: April 8, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Aged between 12 and to 17 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 severity 4)

Exclusion Criteria:

• Acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation
• 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 non-AD inflammatory skin diseases or conditions affecting skin
• Medical history including thrombocytopenia, coagulopathy or platelet dysfunction, malignancies, current or history of certain infections, 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years to 17 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, China, Czechia, Germany, Hungary, Italy, Japan, Latvia, Mexico, Poland, Spain, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT03796676
• Other Study ID Numbers: B7451036; JADE TEEN ( Other Identifier: Alias Study Number ); 2018-003804-37 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: April 2022