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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03349060

Registration number

NCT03349060

Ethics application status

Date submitted

17/11/2017

Date registered

21/11/2017

Date last updated

10/12/2019

Titles & IDs

Public title

Study to Evaluate Efficacy and Safety of PF-04965842 in Subjects Aged 12 Years And Older With Moderate to Severe Atopic Dermatitis

Scientific title

A PHASE 3 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP, MULTI-CENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF PF-04965842 MONOTHERAPY IN SUBJECTS AGED 12 YEARS AND OLDER, WITH MODERATE TO SEVERE ATOPIC DERMATITIS

Secondary ID [1]

2017-003651-29

Secondary ID [2]

B7451012

Universal Trial Number (UTN)

Trial acronym

JADE Mono-1

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Dermatitis, Atopic

Condition category

Condition code

Skin

Dermatological conditions

Skin

Other skin conditions

Inflammatory and Immune System

Other inflammatory or immune system disorders

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Treatment: Drugs - PF-04965842 100 mg
Treatment: Drugs - PF-04965842 200 mg
Treatment: Drugs - Placebo

Experimental: PF-04965842 100 mg -

Experimental: PF-04965842 200 mg -

Placebo comparator: Placebo -

Treatment: Drugs: PF-04965842 100 mg
PF-04965842 100 mg, administered as two tablets to be taken orally once daily for 12 weeks

Treatment: Drugs: PF-04965842 200 mg
PF-04965842 200 mg, administered as two tablets to be taken orally once daily for 12 weeks

Treatment: Drugs: Placebo
Placebo, administered as two tablets to be taken orally once daily for 12 weeks

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of Clear (0) or Almost Clear (1) and Greater Than or Equal to 2 Points Improvement From Baseline at Week 12

Assessment method [1]

IGA assesses severity of AD on a 5 point scale (0 to 4, higher scores indicate more severity). Scores: 0= clear, no inflammatory signs of AD; 1= almost clear, AD not fully cleared- light pink residual lesions (except post-inflammatory hyperpigmentation), just perceptible erythema, papulation/induration lichenification, excoriation, and no oozing/crusting; 2= mild AD with light red lesions, slight but definite erythema, papulation/induration, lichenification, excoriation and no oozing/crusting; 3= moderate AD with red lesions, moderate erythema, papulation/induration, lichenification, excoriation and slight oozing/crusting; 4= severe AD with deep dark red lesions, severe erythema, papulation/induration, lichenification, excoriation and moderate to severe oozing/crusting. Assessment excluded sole, palms and scalp.

Timepoint [1]

Baseline, Week 12

Primary outcome [2]

Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Response of >=75 Percent (%) Improvement From Baseline at Week 12

Assessment method [2]

EASI evaluates severity of participants' AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of body surface area (BSA) affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin)\] and lower limbs \[including buttocks\]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (\>0 to \<10%), 2 (10 to \<30%), 3 (30 to \<50%), 4 (50 to \<70%), 5 (70 to \<90%) and 6 (90 to 100%). Total EASI score =0.1\*Ah\*(Eh+Ih+Exh+Lh) + 0.2\*Au\*(Eu+Iu+ExU+Lu) + 0.3\*At\*(Et+It+Ext+Lt) + 0.4\*Al\*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, higher scores = greater severity of AD.

Timepoint [2]

Baseline, Week 12

Secondary outcome [1]

Percentage of Participants With at Least 4 Points Improvement From Baseline in the Numerical Rating Scale (NRS) for Severity of Pruritus at Week 2, 4, 8 and 12: Full Analysis Set (FAS)

Assessment method [1]

Participants were asked to assess their worst pruritus/itching due to AD over the past 24 hours on an NRS scale ranged from 0 (no itching) to 10 (worst possible itching), where higher scores indicated greater severity.

Timepoint [1]

Baseline, Week 2, 4, 8, 12

Secondary outcome [2]

Percentage of Participants With at Least 4 Points Improvement From Baseline in the Numerical Rating Scale for Severity of Pruritus at Week 2, 4 and 12: Per Protocol Analysis Set (PPAS)

Assessment method [2]

Timepoint [2]

Baseline, Week 2, 4, 12

Secondary outcome [3]

Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) Total Score at Week 2, 4, 8 and 12: Full Analysis Set

Assessment method [3]

PSAAD is a daily participant reported symptom electronic diary. Participants rated their symptoms of AD over the past 24 hours, using 11 items (itchy skin, painful skin, dry skin, flaky skin, cracked skin, bumpy skin, red skin, discolored skin \[lighter or darker\], bleeding from skin, seeping or oozing fluid from skin \[other than blood\], and skin swelling). Participant had to think about all the areas of their body affected by their skin condition and chose the number that best described their experience for each of the 11 items, from 0 (no symptoms) to 10 (extreme symptoms), higher scores signified worse skin condition. Total PSAAD score = arithmetic mean of 11 items, 0 (no symptoms) to 10 (extreme symptoms), where higher score = worse skin condition.

Timepoint [3]

Baseline, Week 2, 4, 8, 12

Secondary outcome [4]

Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis Total Score at Week 12: Per Protocol Analysis Set

Assessment method [4]

Timepoint [4]

Baseline, Week 12

Secondary outcome [5]

Time to Achieve >=4 Points Improvement From Baseline in Numerical Rating Scale for Severity of Pruritus

Assessment method [5]

Participants were asked to assess their worst itching/pruritus due to AD over the past 24 hours on an NRS scale ranged from 0 (no itching) to 10 (worst itch imaginable), where higher scores indicated greater severity. 95% CI was based on the Brookmeyer and Crowley method.

Timepoint [5]

Baseline up to Week 12

Secondary outcome [6]

Percentage of Participants Achieving Eczema Area and Severity Index Response of >=75% Improvement From Baseline at Week 2, 4 and 8

Assessment method [6]

Timepoint [6]

Baseline, Week 2, 4, 8

Secondary outcome [7]

Percentage of Participants Achieving Investigator's Global Assessment Response of Clear (0) or Almost Clear (1) and >=2 Points Improvement From Baseline at Week 2, 4 and 8

Assessment method [7]

Timepoint [7]

Baseline, Week 2, 4, 8

Secondary outcome [8]

Percentage of Participants Achieving Investigator's Global Assessment Response of Clear (0) at Week 2, 4, 8 and 12

Assessment method [8]

Timepoint [8]

Week 2, 4, 8, 12

Secondary outcome [9]

Percentage of Participants Achieving Eczema Area and Severity Index Response of >=50% Improvement From Baseline at Week 2, 4, 8 and 12

Assessment method [9]

Timepoint [9]

Baseline, Week 2, 4, 8, 12

Secondary outcome [10]

Percentage of Participants Achieving Eczema Area and Severity Index Response of >=90% Improvement From Baseline at Week 2, 4, 8 and 12

Assessment method [10]

Timepoint [10]

Baseline, Week 2, 4, 8, 12

Secondary outcome [11]

Percentage of Participants Achieving Eczema Area and Severity Index Response of 100% Improvement From Baseline at Week 2, 4, 8 and 12

Assessment method [11]

Timepoint [11]

Baseline, Week 2, 4, 8, 12

Secondary outcome [12]

Change From Baseline in Eczema Area and Severity Index Total Score at Week 2, 4, 8 and 12

Assessment method [12]

Timepoint [12]

Baseline, Week 2, 4, 8, 12

Secondary outcome [13]

Change From Baseline in Percentage Body Surface Area at Week 2, 4, 8 and 12

Assessment method [13]

4 body regions were evaluated: head and neck, upper limbs, trunk (including axillae and groin) and lower limbs (including buttocks). Scalp, palms and soles were excluded. BSA was calculated using handprint method. Number of handprints (size of participant's hand with fingers in a closed position) fitting in the affected area of a body region was estimated. Maximum number of handprints were 10 for head and neck, 20 for upper limbs, 30 for trunk and 40 for lower limbs. Surface area of body region equivalent to 1 handprint: 1 handprint was equal to 10% for head and neck, 5% for upper limbs, 3.33% for trunk and 2.5% for lower limbs. Percent BSA for a body region was calculated as = total number of handprints in a body region \* % surface area equivalent to 1 handprint. Overall % BSA for an individual: arithmetic mean of % BSA of all 4 body regions, ranges from 0 to 100%, with higher values representing greater severity of AD.

Timepoint [13]

Baseline, Week 2, 4, 8, 12

Secondary outcome [14]

Percentage of Participants With Percentage Body Surface Area Less Than (<) 5% at Week 2, 4, 8 and 12

Assessment method [14]

4 body regions were evaluated: head and neck, upper limbs, trunk (including axillae and groin) and lower limbs (including buttocks). Scalp, palms and soles were excluded. BSA was calculated using handprint method. Number of handprints (size of participant's hand with fingers in a closed position) fitting in the affected area of a body region was estimated. Maximum number of handprints were 10 for head and neck, 20 for upper limbs, 30 for trunk and 40 for lower limbs. Surface area of body region equivalent to 1 handprint: 1 handprint was equal to 10% for head and neck, 5% for upper limb, 3.33% for trunk and 2.5% for lower limb. % BSA for a body region was calculated as = total number of handprints in a body region \* % surface area equivalent to 1 handprint. Overall % BSA for an individual: arithmetic mean of % BSA of all 4 body regions, ranges from 0 to 100%, with higher values representing greater severity of AD.

Timepoint [14]

Week 2, 4, 8, 12

Secondary outcome [15]

Percentage of Participants With Scoring Atopic Dermatitis (SCORAD) Response of >=50% Improvement From Baseline at Week 2, 4, 8 and 12

Assessment method [15]

SCORAD: scoring index for AD combining extent, severity, subjective symptoms. Extent (A): rule of 9 was used to calculate BSA affected by AD as a % of whole BSA for each body region- head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; 1% for genitals. The score for each body region was added to determine A (0-100). Severity (B): severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none=0, mild=1, moderate=2,severe=3. The severity scores were summed to give B (0-18). Subjective symptoms (C): pruritus and sleep, each of these 2 were scored by participant/caregiver using visual analogue scale (VAS) where "0" = no itch/no sleeplessness and "10" = the worst imaginable itch/sleeplessness, higher scores=worse symptoms. Scores for itch and sleeplessness were added to give 'C' (0-20). The SCORAD for an individual was calculated: A/5 + 7\*B/2 + C; range from 0 to 103; higher values of SCORAD=worse outcome.

Timepoint [15]

Baseline, Week 2, 4, 8, 12

Secondary outcome [16]

Percentage of Participants With Scoring Atopic Dermatitis Response of >=75% Improvement From Baseline at Week 2, 4, 8 and 12

Assessment method [16]

SCORAD: scoring index for AD combining extent, severity, subjective symptoms. Extent (A): rule of 9 was used to calculate BSA affected by AD as a % of whole BSA for each body region- head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; 1% for genitals. The score for each body region was added to determine A (0-100). Severity (B): severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none (0), mild (1), moderate (2) or severe (3). The severity scores added to give B (0-18). Subjective symptoms (C): pruritus and sleep loss, each of these 2 were scored by participant/caregiver using VAS where "0" = no itch or no sleeplessness and "10" = the worst imaginable itch or sleeplessness, higher scores worse symptoms. Scores for itch and sleeplessness added to give 'C' (0-20). The SCORAD for an individual was calculated: A/5 + 7\*B/2 + C; range from 0 to 103; higher values of SCORAD = worse outcome.

Timepoint [16]

Baseline, Week 2, 4, 8, 12

Secondary outcome [17]

Change From Baseline in Scoring Atopic Dermatitis: Visual Analogue Scale of Sleep Loss at Week 2, 4, 8 and 12

Assessment method [17]

SCORAD: scoring index for AD combining extent, severity, subjective symptoms. Extent (A): rule of 9 was used to calculate BSA affected by AD as a % of whole BSA for each body region- head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; 1% for genitals. The score for each body region was added to determine A (0-100). Severity (B): severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none (0), mild (1), moderate (2) or severe (3). The severity scores added to give B (0-18). Subjective symptoms (C): pruritus and sleep loss, each of these 2 were scored by participant/caregiver using VAS where "0" = no itch or no sleeplessness and "10" = the worst imaginable itch or sleeplessness, higher scores worse symptoms. Scores for itch and sleeplessness added to give 'C' (0-20). The SCORAD for an individual was calculated: A/5 + 7\*B/2 + C; range from 0 to 103; higher values of SCORAD = worse outcome.

Timepoint [17]

Baseline, Week 2, 4, 8, 12

Secondary outcome [18]

Change From Baseline in Scoring Atopic Dermatitis: Total Score at Week 2, 4, 8 and 12

Assessment method [18]

SCORAD: scoring index for AD combining extent, severity, subjective symptoms. Extent (A): rule of 9 was used to calculate BSA affected by AD as a % of whole BSA for each body region- head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; 1% for genitals. The score for each body region was added to determine A (0-100). Severity (B): severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none (0), mild (1), moderate (2) or severe (3). The severity scores added to give B (0-18). Subjective symptoms (C): pruritus and sleep loss, each of these 2 were scored by participant/caregiver using VAS where "0" = no itch or no sleeplessness and "10" = the worst imaginable itch or sleeplessness, higher scores worse symptoms. Scores for itch and sleeplessness added to give 'C' (0-20). The SCORAD for an individual was calculated: A/5 + 7\*B/2 + C; range from 0 to 103; higher values of SCORAD = worse outcome.

Timepoint [18]

Baseline, Week 2, 4, 8, 12

Secondary outcome [19]

Percentage of Participants Achieving >=1 Point Improvement From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis at Week 2, 4, 8 and 12

Assessment method [19]

Timepoint [19]

Baseline, Week 2, 4, 8, 12

Secondary outcome [20]

Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 2, 4, 8 and 12

Assessment method [20]

DLQI is a 10-item questionnaire that measures the impact of skin disease on participant's (aged above 17 years) quality of life over the last week. Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicated more impact on quality of life. Scores from all 10 questions added up to give DLQI total score range from 0 (not at all) to 30 (very much). Higher scores indicated more impact on quality of life of participants.

Timepoint [20]

Baseline, Week 2, 4, 8, 12

Secondary outcome [21]

Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) at Week 2, 4, 8 and 12

Assessment method [21]

CDLQI is a 10-item questionnaire that measures the impact of skin disease on adolescents (aged 12-17 years) quality of life over the last week. Each question was 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. CDLQI total score was the sum of individual scores of question 1-10 and ranges from 0 (not at all) to 30 (very much). Higher scores indicated more impact on quality of life of children.

Timepoint [21]

Baseline, Week 2, 4, 8, 12

Secondary outcome [22]

Percentage of Participants With Baseline Dermatology Life Quality Index Score >=2 and Achieving <2 DLQI Score at Week 2, 4, 8 and 12

Assessment method [22]

Timepoint [22]

Baseline, Week 2, 4, 8, 12

Secondary outcome [23]

Percentage of Participants With Baseline Children's Dermatology Life Quality Index Score >=2 and Achieving <2 CDLQI Score at Week 2, 4, 8 and 12

Assessment method [23]

Timepoint [23]

Baseline, Week 2, 4, 8, 12

Secondary outcome [24]

Percentage of Participants With Baseline Dermatology Life Quality Index Score >=4 and Achieving >=4 Point Improvement From Baseline in DLQI Score at Week 2, 4, 8 and 12

Assessment method [24]

Timepoint [24]

Baseline, Week 2, 4, 8, 12

Secondary outcome [25]

Percentage of Participants With Baseline Children's Dermatology Life Quality Index Score >=2.5 and Achieving >=2.5 Point Improvement From Baseline in CDLQI Score at Week 2, 4, 8 and 12

Assessment method [25]

Timepoint [25]

Baseline, Week 2, 4, 8, 12

Secondary outcome [26]

Change From Baseline in Hospital Anxiety and Depression Scale (HADS): Depression Subscale at Week 2, 4, 8 and 12

Assessment method [26]

HADS: participant rated 14-item questionnaire. HADS consisted of 2 subscales: HADS-anxiety scale (HADS-A) and HADS-depression scale (HADS-D), both of these subscales comprised of 7 items each. Each item was rated on a 4-point scale, score range from 0 to 3, where higher scores indicates more anxiety/depression symptoms. 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). HADS-D: sum of all 7 items resulted in score range of 0 (no presence of depression) to 21 (severe feeling of depression); higher score indicating greater severity of depression symptoms.

Timepoint [26]

Baseline, Week 2, 4, 8, 12

Secondary outcome [27]

Change From Baseline in Hospital Anxiety and Depression Scale: Anxiety Subscale at Week 2, 4, 8 and 12

Assessment method [27]

HADS: participant rated 14-item questionnaire. HADS consisted of 2 subscales: HADS-anxiety scale (HADS-A) and HADS-depression scale (HADS-D), both of these subscales comprised of 7 items each. Each item was rated on a 4-point scale, score range from 0 to 3, where higher scores indicates more anxiety/depression symptoms. 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). HADS-A: sum of all 7 items resulted in score range of 0 (no presence of anxiety) to 21 (severe feeling of anxiety); higher score indicating greater severity of anxiety.

Timepoint [27]

Baseline, Week 2, 4, 8, 12

Secondary outcome [28]

Percentage of Participants With >=8 Points at Baseline and Achieving Score of <8 Points in Hospital Anxiety and Depression Scale: Anxiety Subscale at Week 2, 4, 8 and 12

Assessment method [28]

HADS: participant rated 14-item questionnaire. HADS consisted of 2 subscales: HADS-anxiety scale (HADS-A) and HADS-depression scale (HADS-D), both of these subscales comprised of 7 items each. Each item was rated on a 4-point scale, score range from 0 to 3, where higher scores indicates more anxiety/depression symptoms. 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). HADS-A: sum of all 7 items resulted in score range of 0 (no presence of anxiety) to 21 (severe feeling of anxiety); higher score indicating greater severity of anxiety.

Timepoint [28]

Baseline, Week 2, 4, 8, 12

Secondary outcome [29]

Percentage of Participants With >=8 Points at Baseline and Achieving Score of <8 Points in Hospital Anxiety and Depression Scale: Depression Subscale at Week 2, 4, 8 and 12

Assessment method [29]

Timepoint [29]

Baseline, Week 2, 4, 8, 12

Secondary outcome [30]

Percentage of Participants With >=11 Points at Baseline and Achieving Score of <11 Points in Hospital Anxiety and Depression Scale: Anxiety Subscale at Week 2, 4, 8 and 12

Assessment method [30]

HADS: participant rated 14-item questionnaire. HADS consisted of 2 subscales: HADS-anxiety scale (HADS-A) and HADS-depression scale (HADS-D), both of these subscales comprised of 7 items each. Each item was rated on a 4-point scale, score range from 0 to 3, where higher scores indicates more anxiety/depression symptoms. 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). HADS-A: sum of all 7 items resulted in score range of 0 (no presence of anxiety) to 21 (severe feeling of anxiety); higher score indicating greater severity of anxiety.

Timepoint [30]

Baseline, Week 2, 4, 8, 12

Secondary outcome [31]

Percentage of Participants With >=11 Points at Baseline and Achieving Score of <11 Points in Hospital Anxiety and Depression Scale: Depression Subscale at Week 2, 4, 8 and 12

Assessment method [31]

Timepoint [31]

Baseline, Week 2, 4, 8, 12

Secondary outcome [32]

Change From Baseline in Patient-Oriented Eczema Measure (POEM) at Week 2, 4, 8 and 12

Assessment method [32]

POEM is a 7-item participant reported outcome (PRO) measure used to assess the impact of AD (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) 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, where higher score indicated greater severity.

Timepoint [32]

Baseline, Week 2, 4, 8, 12

Secondary outcome [33]

Change From Baseline in Patient Global Assessment (PtGA) at Week 2, 4, 8 and 12

Assessment method [33]

Participant responded to "Overall, how would you describe your Atopic Dermatitis right now?" on a scale: 0= clear; 1= almost clear; 2= mild; 3= moderate; and 4= severe. Higher scores indicated more severity.

Timepoint [33]

Baseline, Week 2, 4, 8, 12

Secondary outcome [34]

Percentage of Participants Achieving 'Clear' or 'Almost Clear' and >=2 Points Improvement From Baseline in Patient Global Assessment (PtGA) at Week 2, 4, 8 and 12

Assessment method [34]

Timepoint [34]

Baseline, Week 2, 4, 8, 12

Secondary outcome [35]

Change From Baseline in EuroQol Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L): Index Value at Week 2, 4, 8 and 12

Assessment method [35]

EQ-5D-5L: standardized participant (aged \>17 years) completed questionnaire consisted of 2 components: a health state profile and an optional VAS. EQ-5D health state profile had 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems. Responses to 5 dimensions comprised a health state/a single utility index value. E.g. if a participant responded "no problems" for each 5 dimensions, then health state was coded as "11111" with a predefined index value to it. Every health state (coded as combination of responses on each of 5 dimensions) had a unique predefined utility index value assigned to it, by EuroQol. US value sets (with all possible health states) was used for adults in the study, range from 1 to -0.109. Higher (positive) scores = better health state.

Timepoint [35]

Baseline, Week 2, 4, 8, 12

Secondary outcome [36]

Change From Baseline in EuroQol Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L)- Visual Analogue Scale Score at Week 2, 4, 8 and 12

Assessment method [36]

EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional VAS. EQ-5D VAS was used to record a participant's (aged above 17 years) rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0 = worst imaginable health state and 100 = best imaginable health state.

Timepoint [36]

Baseline, Week 2, 4, 8, 12

Secondary outcome [37]

Change From Baseline in EuroQol Quality of Life 5-Dimension Youth Scale (EQ-5D-Y): Index Value at Week 2, 4, 8 and 12

Assessment method [37]

EQ-5D-Y: standardized participant (aged 12-17 years) completed questionnaire consisted of 2 components: a health state profile and an optional VAS. EQ-5D health state profile had 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems. Responses to 5 dimensions comprised a health state/a single utility index value. E.g. if a participant responded "no problems" for each 5 dimensions, then health state was coded as "11111" with a predefined index value to it. Every health state (coded as combination of responses on each of 5 dimensions) had a unique predefined utility index value assigned to it, by EuroQol. UK value sets (with all possible health states) was used for adolescents in the study, range from 1 to -0.594. Higher (positive) scores = better health state.

Timepoint [37]

Baseline, Week 2, 4, 8, 12

Secondary outcome [38]

Change From Baseline in EuroQol Quality of Life 5-Dimension Youth Scale (EQ-5D-Y): Visual Analogue Scale Score at Week 2, 4, 8 and 12

Assessment method [38]

EQ-5D-Y is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score specifically developed and validated for use by youths age 12-17 years. EQ-5D-Y consists of two components: a health state profile and an optional VAS. EQ-5D VAS was used to record a participant's rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0 = worst imaginable health state and 100 = best imaginable health state.

Timepoint [38]

Baseline, Week 2, 4, 8, 12

Secondary outcome [39]

Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F) at Week 12

Assessment method [39]

FACIT-F is a 13-item questionnaire. Participants (aged above 17 years) scored each item on a 5-point scale: 0 (not at all) to 4 (very much). Higher 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 (the best score) where higher scores indicated better overall health status (less fatigue).

Timepoint [39]

Baseline, Week 12

Secondary outcome [40]

Change From Baseline in Pediatric Functional Assessment of Chronic Illness Therapy Fatigue Scale (Peds-FACIT-F) at Week 12

Assessment method [40]

Peds-FACIT-F is a 13-item questionnaire for adolescents of 12-17 years of age. Participants scored each item on a 5-point scale: 0 (none of the time) to 4 (all of the time). Higher 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 Peds-FACIT-F score for a total possible score of 0 (worse score) to 52 (the best score) where higher scores indicated better overall health status (less fatigue).

Timepoint [40]

Baseline, Week 12

Secondary outcome [41]

Change From Baseline in Short Form-36v2 (SF-36v2) Acute Summary Score at Week 12: Physical Component Summary

Assessment method [41]

SF-36v2 health survey is a self-administered questionnaire consisting of 36 questions, measuring 8 health domains: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. These domains were also summarized as physical and mental component summary scores. Physical component summary: the minimum score is 0 and the maximum score is 100. Higher scores indicates a better health state.

Timepoint [41]

Baseline, Week 12

Secondary outcome [42]

Change From Baseline in Short Form-36v2 Acute Summary Score at Week 12: Mental Component Summary

Assessment method [42]

SF-36v2 health survey is a self-administered questionnaire consisting of 36 questions, measuring 8 health domains: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. These domains were also summarized as physical and mental component summary scores. Mental component summary: the minimum score is 0 and the maximum score is 100. Higher scores indicates a better health state.

Timepoint [42]

Baseline, Week 12

Secondary outcome [43]

Plasma Concentration Versus Time Summary of PF-04965842

Assessment method [43]

Concentration versus time summary was calculated by setting concentration values below the lower limit of quantification (LLQ) = =1.00 nanogram per milliliter (ng/mL) to zero.

Timepoint [43]

Day 1 of Week 4: 0 hour(Pre-dose), 0.5 hours post-dose; Day 1 of Week 12: 0.5, 4 hours post-dose

Eligibility

Key inclusion criteria

* 12 years of age or older 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 4)
* Recent history of inadequate response or inability to tolerate topical AD treatments or require systemic treatments for AD control

Minimum age

12 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

* 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 nonAD inflammatory skin diseases or conditions affecting skin
* Medical history including thrombocytopenia, coagulopathy or platelet dysfunction, Q wave interval abnormalities, current or history of certain infections, cancer, 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

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Phase 3

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Data analysis

Reason for early stopping/withdrawal

Other reasons

Date of first participant enrolment

Anticipated

Actual

7/12/2017

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

26/03/2019

Sample size

Target

Accrual to date

Final

387

Recruitment in Australia

Recruitment state(s)

NSW,QLD,VIC

Recruitment hospital [1]

Australian Clinical Research Network (ACRN) - Maroubra

Recruitment hospital [2]

Spectrum Medical Imaging - Maroubra

Recruitment hospital [3]

Queensland X-Ray - Upper Mount Gravatt

Recruitment hospital [4]

Veracity Clinical Research Pty Ltd - Woolloongabba

Recruitment hospital [5]

Emeritus Research - Camberwell

Recruitment hospital [6]

Skin and Cancer Foundation Inc - Carlton

Recruitment hospital [7]

Melbourne Radiology Clinic - East Melbourne

Recruitment hospital [8]

Sinclair Dermatology - East Melbourne

Recruitment hospital [9]

The Royal Children's Hospital - Parkville

Recruitment hospital [10]

Bridge Road Imaging - Richmond

Recruitment postcode(s) [1]

2035 - Maroubra

Recruitment postcode(s) [2]

4122 - Upper Mount Gravatt

Recruitment postcode(s) [3]

4102 - Woolloongabba

Recruitment postcode(s) [4]

3124 - Camberwell

Recruitment postcode(s) [5]

3053 - Carlton

Recruitment postcode(s) [6]

3002 - East Melbourne

Recruitment postcode(s) [7]

3052 - Parkville

Recruitment postcode(s) [8]

3121 - Richmond

Recruitment outside Australia

Country [1]

United States of America

State/province [1]

Alabama

Country [2]

United States of America

State/province [2]

California

Country [3]

United States of America

State/province [3]

Florida

Country [4]

United States of America

State/province [4]

Georgia

Country [5]

United States of America

State/province [5]

Illinois

Country [6]

United States of America

State/province [6]

Indiana

Country [7]

United States of America

State/province [7]

Massachusetts

Country [8]

United States of America

State/province [8]

Michigan

Country [9]

United States of America

State/province [9]

Missouri

Country [10]

United States of America

State/province [10]

Oklahoma

Country [11]

United States of America

State/province [11]

Oregon

Country [12]

United States of America

State/province [12]

South Carolina

Country [13]

United States of America

State/province [13]

Texas

Country [14]

United States of America

State/province [14]

Virginia

Country [15]

United States of America

State/province [15]

Washington

Country [16]

Canada

State/province [16]

Alberta

Country [17]

Canada

State/province [17]

British Columbia

Country [18]

Canada

State/province [18]

Manitoba

Country [19]

Canada

State/province [19]

Ontario

Country [20]

Canada

State/province [20]

Quebec

Country [21]

Czechia

State/province [21]

Kutna Hora

Country [22]

Czechia

State/province [22]

Ostrava - Poruba

Country [23]

Czechia

State/province [23]

Praha 1

Country [24]

Czechia

State/province [24]

Praha 2

Country [25]

Czechia

State/province [25]

Usti nad Labem

Country [26]

Germany

State/province [26]

Schleswig-holstein

Country [27]

Germany

State/province [27]

Bad Bentheim

Country [28]

Germany

State/province [28]

Berlin

Country [29]

Germany

State/province [29]

Dresden

Country [30]

Germany

State/province [30]

Erlangen

Country [31]

Germany

State/province [31]

Kiel

Country [32]

Germany

State/province [32]

Munich

Country [33]

Germany

State/province [33]

Münster

Country [34]

Germany

State/province [34]

Schwerin

Country [35]

Hungary

State/province [35]

Bács-kiskun

Country [36]

Hungary

State/province [36]

Debrecen

Country [37]

Hungary

State/province [37]

Kecskemet

Country [38]

Hungary

State/province [38]

Miskolc

Country [39]

Hungary

State/province [39]

Pecs

Country [40]

Poland

State/province [40]

Katowice

Country [41]

Poland

State/province [41]

Lodz

Country [42]

Poland

State/province [42]

Ostrowiec Swietokrzyski

Country [43]

Poland

State/province [43]

Warszawa

Country [44]

United Kingdom

State/province [44]

Devon

Country [45]

United Kingdom

State/province [45]

Greater London

Country [46]

United Kingdom

State/province [46]

South Yorkshire, England

Country [47]

United Kingdom

State/province [47]

South Yorkshire

Country [48]

United Kingdom

State/province [48]

Dudley

Funding & Sponsors

Primary sponsor type

Commercial sector/industry

Name

Pfizer

Country

Ethics approval

Ethics application status

Summary

Brief summary

B7451012 is a Phase 3 study to evaluate PF-04965842 in patients aged 12 years and older with a minimum body weight of 40 kg who have moderate to severe atopic dermatitis. The efficacy and safety of two dosage strengths of PF-04965842, 100 mg and 200 mg taken orally once daily, will be evaluated relative to placebo over 12 weeks of study participation. Eligible patients will have an option to enter a long-term extension study after completing 12 weeks of treatment.

Trial website

https://clinicaltrials.gov/study/NCT03349060

Trial related presentations / publications

Blauvelt A, Boguniewicz M, Brunner PM, Luna PC, Biswas P, DiBonaventura M, Farooqui SA, Rojo R, Cameron MC. Abrocitinib monotherapy in Investigator's Global Assessment nonresponders: improvement in signs and symptoms of atopic dermatitis and quality of life. J Dermatolog Treat. 2022 Aug;33(5):2605-2613. doi: 10.1080/09546634.2022.2059053. Epub 2022 Jul 6.
Stander S, Bhatia N, Gooderham MJ, Silverberg JI, Thyssen JP, Biswas P, DiBonaventura M, Romero W, Farooqui SA. High threshold efficacy responses in moderate-to-severe atopic dermatitis are associated with additional quality of life benefits: pooled analyses of abrocitinib monotherapy studies in adults and adolescents. J Eur Acad Dermatol Venereol. 2022 Aug;36(8):1308-1317. doi: 10.1111/jdv.18170. Epub 2022 May 6.
Wojciechowski J, Malhotra BK, Wang X, Fostvedt L, Valdez H, Nicholas T. Population pharmacokinetic-pharmacodynamic modelling of platelet time-courses following administration of abrocitinib. Br J Clin Pharmacol. 2022 Aug;88(8):3856-3871. doi: 10.1111/bcp.15334. Epub 2022 Apr 11.
Wojciechowski J, Malhotra BK, Wang X, Fostvedt L, Valdez H, Nicholas T. Population Pharmacokinetics of Abrocitinib in Healthy Individuals and Patients with Psoriasis or Atopic Dermatitis. Clin Pharmacokinet. 2022 May;61(5):709-723. doi: 10.1007/s40262-021-01104-z. Epub 2022 Jan 21. Erratum In: Clin Pharmacokinet. 2022 Apr;61(4):591. doi: 10.1007/s40262-022-01112-7.
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.
Simpson EL, Silverberg JI, Nosbaum A, Winthrop KL, Guttman-Yassky E, Hoffmeister KM, Egeberg A, Valdez H, Zhang M, Farooqui SA, Romero W, Thorpe AJ, Rojo R, Johnson S. Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program. Am J Clin Dermatol. 2021 Sep;22(5):693-707. doi: 10.1007/s40257-021-00618-3. Epub 2021 Aug 18. Erratum In: Am J Clin Dermatol. 2021 Nov;22(6):905. doi: 10.1007/s40257-021-00638-z.
Silverberg JI, Thyssen JP, Simpson EL, Yosipovitch G, Stander S, Valdez H, Rojo R, Biswas P, Myers DE, Feeney C, DiBonaventura M. Impact of Oral Abrocitinib Monotherapy on Patient-Reported Symptoms and Quality of Life in Adolescents and Adults with Moderate-to-Severe Atopic Dermatitis: A Pooled Analysis of Patient-Reported Outcomes. Am J Clin Dermatol. 2021 Jul;22(4):541-554. doi: 10.1007/s40257-021-00604-9. Epub 2021 May 5. Erratum In: Am J Clin Dermatol. 2021 Sep;22(5):739. doi: 10.1007/s40257-021-00634-3.
Simpson EL, Sinclair R, Forman S, Wollenberg A, Aschoff R, Cork M, Bieber T, Thyssen JP, Yosipovitch G, Flohr C, Magnolo N, Maari C, Feeney C, Biswas P, Tatulych S, Valdez H, Rojo R. Efficacy and safety of abrocitinib in adults and adolescents with moderate-to-severe atopic dermatitis (JADE MONO-1): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet. 2020 Jul 25;396(10246):255-266. doi: 10.1016/S0140-6736(20)30732-7.

Public notes

Contacts

Principal investigator

Name

Pfizer CT.gov Call Center

Address

Pfizer

Country

Phone

Contact person for public queries

Name

Address

Country

Phone

Contact person for scientific queries

Data sharing statement

What supporting documents are/will be available?

Type	Other Details	Attachment
Statistical analysis plan		https://cdn.clinicaltrials.gov/large-docs/60/NCT03349060/SAP_000.pdf
Study protocol		https://cdn.clinicaltrials.gov/large-docs/60/NCT03349060/Prot_001.pdf

Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT03349060

Trial Review

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03349060