Dermatitis, Atopic
Conditions
Keywords
atopic dermatitis, atopic eczema, eczema, JAK, janus kinase
Brief summary
B7451013 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.
Interventions
PF-04965842 100 mg, administered as two tablets to be taken orally once daily for 12 weeks
PF-04965842 200 mg, administered as two tablets to be taken orally once daily for 12 weeks
DRUGPlacebo
Placebo, administered as two tablets to be taken orally once daily for 12 weeks
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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 severity 4) * Recent history of inadequate response or inability to tolerate topical AD treatments or require systemic treatments for AD control
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline, Week 12 | 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 soles, palms and scalp. |
| Percentage of Participants Achieving Eczema Area and Severity Index Response of >=75 Percent (%) Improvement (EASI-75) From Baseline at Week 12 | Baseline, Week 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Achieve >=4 Points Improvement From Baseline in Numerical Rating Scale (NRS) for Severity of Pruritus | Baseline up to Day 15 | 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. |
| Percentage of Participants Achieving Eczema Area and Severity Index Response of >=75% Improvement (EASI-75) From Baseline at Weeks 2, 4 and 8 | Baseline, Weeks 2, 4, and 8 | 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. |
| Percentage of Participants Achieving IGA Response of Clear (0) or Almost Clear (1) and >=2 Points Improvement From Baseline at Weeks 2, 4 and 8 | Baseline, Weeks 2, 4, and 8 | 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. |
| Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of Clear (0) at Week 2, 4, 8 and 12 | Weeks 2, 4, 8 and 12 | 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 soles, palms and scalp. |
| Percentage of Participants Achieving Eczema Area and Severity Index Response of >=50% Improvement (EASI-50) From Baseline at Weeks 2, 4, 8 and 12 | Baseline, Weeks 2, 4, 8, and 12 | 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. |
| Percentage of Participants Achieving Eczema Area and Severity Index Response of >=90% Improvement (EASI-90) From Baseline at Weeks 2, 4, 8 and 12 | Baseline, Weeks 2, 4, 8, and 12 | 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. |
| Percentage of Participants Achieving Eczema Area and Severity Index Response of 100% Improvement (EASI-100) From Baseline at Weeks 2, 4, 8 and 12 | Baseline, Weeks 2, 4, 8, and 12 | EASI evaluates severity of participant's 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. |
| Percentage of Participants Who Achieved at Least 4-Points Improvement From Baseline in the Numerical Rating Scale (NRS) for Severity of Pruritus at Weeks 2, 4, 8 and 12 | Baseline, Weeks 2, 4, 8 and 12 | 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. |
| Change From Baseline in the Percentage Body Surface Area (%BSA) Affected at Week 2, 4, 8, and 12 | Baseline, Weeks 2, 4, 8, and 12 | 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. |
| Percentage of Participants With Percentage Body Surface Area (%BSA) (From EASI) < 5% at Weeks 2, 4, 8 and 12 | Weeks 2, 4, 8, and 12 | 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. |
| Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=50% Improvement From Baseline at Week 2, 4, 8 and 12 | Baseline, Weeks 2, 4, 8, and 12 | 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. |
| Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=75% Improvement From Baseline at Week 2, 4, 8 and 12 | Baseline, Weeks 2, 4, 8, and 12 | 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. |
| Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) of Itch at Weeks 2, 4, 8 and 12 | Baseline, Weeks 2, 4, 8, and 12 | 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. |
| Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) Sleep Loss at Weeks 2, 4, 8 and 12 | Baseline, Weeks 2, 4, 8, and 12 | 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. |
| Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Total Score at Week 2, 4, 8 and 12 | Baseline, Weeks 2, 4, 8, and 12 | 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. |
| Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 2, 4, 8 and 12 | Baseline, Weeks 2, 4, 8, and 12 | EASI evaluates severity of participant's 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. |
| Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) Total Score at Week 12 | Baseline, Week 12 | 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. |
Countries
Australia, Bulgaria, Canada, China, Czechia, Germany, Hungary, Japan, Latvia, Poland, South Korea, United Kingdom, United States
Participant flow
Recruitment details
Participants with age greater than or equal to (\>=) 12 years with moderate to severe atopic dermatitis (AD) and a body weight of \>=40 kilograms were enrolled in the study. Eligible participants had an option to enter into a long-term extension (LTE) study after completing 12 weeks of treatment in this study.
Pre-assignment details
This study was conducted from 29-June-2018 to 13-Aug-2019 at 106 sites in 13 countries.
Participants by arm
| Arm | Count |
|---|---|
| PF-04965842 100 mg Participants were randomized to receive a tablet of PF-04965842 (abrocitinib) 100 milligrams (mg) and a tablet of matching placebo orally once daily for 12 weeks. Participants who discontinued early from treatment or who were not eligible for LTE study, were followed up to 4 weeks after last dose of study drug. | 158 |
| PF-04965842 200 mg Participants were randomized to receive PF-04965842 200 mg (2 tablets of 100 mg each) orally once daily for 12 weeks. Participants who discontinued early from treatment or who were not eligible for LTE study, were followed up to 4 weeks after last dose of study drug. | 155 |
| Placebo Participants were randomized to receive 2 tablets of placebo matched to PF-04965842 100 mg orally once daily for 12 weeks. Participants who discontinued early from treatment or who were not eligible for LTE study, were followed up to 4 weeks after last dose of study drug. | 78 |
| Total | 391 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 5 | 8 |
| Overall Study | Death | 1 | 0 | 0 |
| Overall Study | Lack of Efficacy | 5 | 4 | 7 |
| Overall Study | Lost to Follow-up | 1 | 1 | 1 |
| Overall Study | Other than specified | 2 | 2 | 0 |
| Overall Study | Protocol Deviation | 1 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 1 | 9 |
Baseline characteristics
| Characteristic | PF-04965842 100 mg | PF-04965842 200 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 37.4 years STANDARD_DEVIATION 15.8 | 33.5 years STANDARD_DEVIATION 14.7 | 33.4 years STANDARD_DEVIATION 13.8 | 35.1 years STANDARD_DEVIATION 15.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 2 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 154 Participants | 150 Participants | 73 Participants | 377 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 46 Participants | 54 Participants | 29 Participants | 129 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 6 Participants | 6 Participants | 21 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) White | 101 Participants | 91 Participants | 40 Participants | 232 Participants |
| Sex: Female, Male Female | 64 Participants | 67 Participants | 31 Participants | 162 Participants |
| Sex: Female, Male Male | 94 Participants | 88 Participants | 47 Participants | 229 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 158 | 0 / 155 | 0 / 78 |
| other Total, other adverse events | 56 / 158 | 52 / 155 | 22 / 78 |
| serious Total, serious adverse events | 5 / 158 | 2 / 155 | 1 / 78 |
Outcome results
Primary
Percentage of Participants Achieving Eczema Area and Severity Index Response of >=75 Percent (%) Improvement (EASI-75) From Baseline at Week 12
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.
Time frame: Baseline, Week 12
Population: Full analysis set included all randomized participants who received at least 1 dose of study medication. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-04965842 100 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=75 Percent (%) Improvement (EASI-75) From Baseline at Week 12 | 44.5 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=75 Percent (%) Improvement (EASI-75) From Baseline at Week 12 | 61.0 percentage of participants |
| Placebo | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=75 Percent (%) Improvement (EASI-75) From Baseline at Week 12 | 10.4 percentage of participants |
Comparison: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [23.3, 44.4]Cochran-Mantel-Haenszel
Comparison: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [40, 60.9]Cochran-Mantel-Haenszel
Primary
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
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 soles, palms and scalp.
Time frame: Baseline, Week 12
Population: Full analysis set included all randomized participants who received at least 1 dose of study medication. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-04965842 100 mg | 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 | 28.4 percentage of participants |
| PF-04965842 200 mg | 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 | 38.1 percentage of participants |
| Placebo | 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 | 9.1 percentage of participants |
Comparison: The estimate and confidence interval (CI) for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.000895% CI: [9.6, 29]Cochran-Mantel-Haenszel
Comparison: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [18.6, 38.8]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) Total Score at Week 12
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.
Time frame: Baseline, Week 12
Population: Full analysis set included all randomized participants who received at least 1 dose of study medication. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PF-04965842 100 mg | Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) Total Score at Week 12 | -2.4 units on a scale |
| PF-04965842 200 mg | Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) Total Score at Week 12 | -3.0 units on a scale |
| Placebo | Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) Total Score at Week 12 | -0.8 units on a scale |
Comparison: Mixed Model Repeated Measure (MMRM) contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category), baseline value and an unstructured covariance matrix.p-value: <0.000195% CI: [-2.3, -1.1]Mixed Models Analysis
Comparison: Mixed Model Repeated Measure (MMRM) contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category), baseline value and an unstructured covariance matrix.p-value: <0.000195% CI: [-2.8, -1.6]Mixed Models Analysis
Secondary
Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) of Itch at Weeks 2, 4, 8 and 12
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.
Time frame: Baseline, Weeks 2, 4, 8, and 12
Population: Full analysis set included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| PF-04965842 100 mg | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) of Itch at Weeks 2, 4, 8 and 12 | Change at Week 2 | -2.3 units on a scale |
| PF-04965842 100 mg | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) of Itch at Weeks 2, 4, 8 and 12 | Change at Week 4 | -3.1 units on a scale |
| PF-04965842 100 mg | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) of Itch at Weeks 2, 4, 8 and 12 | Change at Week 8 | -3.4 units on a scale |
| PF-04965842 100 mg | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) of Itch at Weeks 2, 4, 8 and 12 | Change at Week 12 | -3.5 units on a scale |
| PF-04965842 200 mg | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) of Itch at Weeks 2, 4, 8 and 12 | Change at Week 12 | -4.2 units on a scale |
| PF-04965842 200 mg | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) of Itch at Weeks 2, 4, 8 and 12 | Change at Week 2 | -3.5 units on a scale |
| PF-04965842 200 mg | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) of Itch at Weeks 2, 4, 8 and 12 | Change at Week 8 | -4.3 units on a scale |
| PF-04965842 200 mg | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) of Itch at Weeks 2, 4, 8 and 12 | Change at Week 4 | -4.3 units on a scale |
| Placebo | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) of Itch at Weeks 2, 4, 8 and 12 | Change at Week 12 | -2.1 units on a scale |
| Placebo | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) of Itch at Weeks 2, 4, 8 and 12 | Change at Week 4 | -1.2 units on a scale |
| Placebo | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) of Itch at Weeks 2, 4, 8 and 12 | Change at Week 8 | -1.8 units on a scale |
| Placebo | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) of Itch at Weeks 2, 4, 8 and 12 | Change at Week 2 | -0.6 units on a scale |
Comparison: Week 2: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category), baseline value and an unstructured covariance matrix.p-value: <0.000195% CI: [-2.3, -1.1]Mixed Models Analysis
Comparison: Week 2: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category), baseline value and an unstructured covariance matrix.p-value: <0.000195% CI: [-3.5, -2.3]Mixed Models Analysis
Comparison: Week 4: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category), baseline value and an unstructured covariance matrix.p-value: <0.000195% CI: [-2.6, -1.3]Mixed Models Analysis
Comparison: Week 4: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category), baseline value and an unstructured covariance matrix.p-value: <0.000195% CI: [-3.8, -2.5]Mixed Models Analysis
Comparison: Week 8: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category), baseline value and an unstructured covariance matrix.p-value: <0.000195% CI: [-2.3, -0.9]Mixed Models Analysis
Comparison: Week 8: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category), baseline value and an unstructured covariance matrix.p-value: <0.000195% CI: [-3.3, -1.9]Mixed Models Analysis
Comparison: Week 12: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category), baseline value and an unstructured covariance matrix.p-value: 0.000695% CI: [-2.2, -0.6]Mixed Models Analysis
Comparison: Week 12: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category), baseline value and an unstructured covariance matrix.p-value: <0.000195% CI: [-3, -1.4]Mixed Models Analysis
Secondary
Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) Sleep Loss at Weeks 2, 4, 8 and 12
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.
Time frame: Baseline, Weeks 2, 4, 8, and 12
Population: Full analysis set included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| PF-04965842 100 mg | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) Sleep Loss at Weeks 2, 4, 8 and 12 | Change at Week 2 | -1.9 units on a scale |
| PF-04965842 100 mg | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) Sleep Loss at Weeks 2, 4, 8 and 12 | Change at Week 4 | -2.8 units on a scale |
| PF-04965842 100 mg | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) Sleep Loss at Weeks 2, 4, 8 and 12 | Change at Week 8 | -3.1 units on a scale |
| PF-04965842 100 mg | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) Sleep Loss at Weeks 2, 4, 8 and 12 | Change at Week 12 | -3.0 units on a scale |
| PF-04965842 200 mg | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) Sleep Loss at Weeks 2, 4, 8 and 12 | Change at Week 12 | -3.8 units on a scale |
| PF-04965842 200 mg | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) Sleep Loss at Weeks 2, 4, 8 and 12 | Change at Week 2 | -2.9 units on a scale |
| PF-04965842 200 mg | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) Sleep Loss at Weeks 2, 4, 8 and 12 | Change at Week 8 | -3.9 units on a scale |
| PF-04965842 200 mg | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) Sleep Loss at Weeks 2, 4, 8 and 12 | Change at Week 4 | -3.9 units on a scale |
| Placebo | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) Sleep Loss at Weeks 2, 4, 8 and 12 | Change at Week 12 | -2.1 units on a scale |
| Placebo | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) Sleep Loss at Weeks 2, 4, 8 and 12 | Change at Week 4 | -1.0 units on a scale |
| Placebo | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) Sleep Loss at Weeks 2, 4, 8 and 12 | Change at Week 8 | -1.5 units on a scale |
| Placebo | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) Sleep Loss at Weeks 2, 4, 8 and 12 | Change at Week 2 | -0.5 units on a scale |
Comparison: Week 2: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category), baseline value and an unstructured covariance matrix.p-value: <0.000195% CI: [-2, -0.8]Mixed Models Analysis
Comparison: Week 2: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category), baseline value and an unstructured covariance matrix.p-value: <0.000195% CI: [-3, -1.8]Mixed Models Analysis
Comparison: Week 4: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category), baseline value and an unstructured covariance matrix.p-value: <0.000195% CI: [-2.4, -1.2]Mixed Models Analysis
Comparison: Week 4: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category), baseline value and an unstructured covariance matrix.p-value: <0.000195% CI: [-3.6, -2.3]Mixed Models Analysis
Comparison: Week 8: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category), baseline value and an unstructured covariance matrix.p-value: <0.000195% CI: [-2.3, -0.9]Mixed Models Analysis
Comparison: Week 8: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category), baseline value and an unstructured covariance matrix.p-value: <0.000195% CI: [-3.1, -1.7]Mixed Models Analysis
Comparison: Week 12: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category), baseline value and an unstructured covariance matrix.p-value: 0.016495% CI: [-1.7, -0.2]Mixed Models Analysis
Comparison: Week 12: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category), baseline value and an unstructured covariance matrix.p-value: <0.000195% CI: [-2.5, -1]Mixed Models Analysis
Secondary
Change From Baseline in the Percentage Body Surface Area (%BSA) Affected at Week 2, 4, 8, and 12
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.
Time frame: Baseline, Weeks 2, 4, 8, and 12
Population: Full analysis set included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| PF-04965842 100 mg | Change From Baseline in the Percentage Body Surface Area (%BSA) Affected at Week 2, 4, 8, and 12 | Change at Week 2 | -27.8 percentage of BSA |
| PF-04965842 100 mg | Change From Baseline in the Percentage Body Surface Area (%BSA) Affected at Week 2, 4, 8, and 12 | Change at Week 4 | -45.0 percentage of BSA |
| PF-04965842 100 mg | Change From Baseline in the Percentage Body Surface Area (%BSA) Affected at Week 2, 4, 8, and 12 | Change at Week 8 | -53.4 percentage of BSA |
| PF-04965842 100 mg | Change From Baseline in the Percentage Body Surface Area (%BSA) Affected at Week 2, 4, 8, and 12 | Change at Week 12 | -56.4 percentage of BSA |
| PF-04965842 200 mg | Change From Baseline in the Percentage Body Surface Area (%BSA) Affected at Week 2, 4, 8, and 12 | Change at Week 12 | -65.0 percentage of BSA |
| PF-04965842 200 mg | Change From Baseline in the Percentage Body Surface Area (%BSA) Affected at Week 2, 4, 8, and 12 | Change at Week 2 | -35.4 percentage of BSA |
| PF-04965842 200 mg | Change From Baseline in the Percentage Body Surface Area (%BSA) Affected at Week 2, 4, 8, and 12 | Change at Week 8 | -61.1 percentage of BSA |
| PF-04965842 200 mg | Change From Baseline in the Percentage Body Surface Area (%BSA) Affected at Week 2, 4, 8, and 12 | Change at Week 4 | -55.7 percentage of BSA |
| Placebo | Change From Baseline in the Percentage Body Surface Area (%BSA) Affected at Week 2, 4, 8, and 12 | Change at Week 12 | -16.8 percentage of BSA |
| Placebo | Change From Baseline in the Percentage Body Surface Area (%BSA) Affected at Week 2, 4, 8, and 12 | Change at Week 4 | -15.3 percentage of BSA |
| Placebo | Change From Baseline in the Percentage Body Surface Area (%BSA) Affected at Week 2, 4, 8, and 12 | Change at Week 8 | -20.5 percentage of BSA |
| Placebo | Change From Baseline in the Percentage Body Surface Area (%BSA) Affected at Week 2, 4, 8, and 12 | Change at Week 2 | -1.3 percentage of BSA |
Comparison: Change at Week 2: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.p-value: <0.000195% CI: [-35.5, -17.5]Mixed Models Analysis
Comparison: Change at Week 2: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.p-value: <0.000195% CI: [-43.1, -25.1]Mixed Models Analysis
Comparison: Change at Week 4: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.p-value: <0.000195% CI: [-39, -20.4]Mixed Models Analysis
Comparison: Change at Week 4: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.p-value: <0.000195% CI: [-49.8, -31.1]Mixed Models Analysis
Comparison: Change at Week 8: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.p-value: <0.000195% CI: [-44.6, -21.2]Mixed Models Analysis
Comparison: Change at Week 8: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.p-value: <0.000195% CI: [-52.2, -28.9]Mixed Models Analysis
Comparison: Change at Week 12: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.p-value: <0.000195% CI: [-51.8, -27.4]Mixed Models Analysis
Comparison: Change at Week 12: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.p-value: <0.000195% CI: [-60.4, -36]Mixed Models Analysis
Secondary
Percentage of Participants Achieving Eczema Area and Severity Index Response of 100% Improvement (EASI-100) From Baseline at Weeks 2, 4, 8 and 12
EASI evaluates severity of participant's 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.
Time frame: Baseline, Weeks 2, 4, 8, and 12
Population: Full analysis set included all randomized participants who received at least 1 dose of study medication. Here, Number Analyzed signifies number of participants evaluable at specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04965842 100 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of 100% Improvement (EASI-100) From Baseline at Weeks 2, 4, 8 and 12 | Week 2 | 0 percentage of participants |
| PF-04965842 100 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of 100% Improvement (EASI-100) From Baseline at Weeks 2, 4, 8 and 12 | Week 4 | 1.3 percentage of participants |
| PF-04965842 100 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of 100% Improvement (EASI-100) From Baseline at Weeks 2, 4, 8 and 12 | Week 8 | 1.3 percentage of participants |
| PF-04965842 100 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of 100% Improvement (EASI-100) From Baseline at Weeks 2, 4, 8 and 12 | Week 12 | 5.2 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of 100% Improvement (EASI-100) From Baseline at Weeks 2, 4, 8 and 12 | Week 12 | 7.1 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of 100% Improvement (EASI-100) From Baseline at Weeks 2, 4, 8 and 12 | Week 2 | 1.3 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of 100% Improvement (EASI-100) From Baseline at Weeks 2, 4, 8 and 12 | Week 8 | 3.9 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of 100% Improvement (EASI-100) From Baseline at Weeks 2, 4, 8 and 12 | Week 4 | 3.9 percentage of participants |
| Placebo | Percentage of Participants Achieving Eczema Area and Severity Index Response of 100% Improvement (EASI-100) From Baseline at Weeks 2, 4, 8 and 12 | Week 12 | 0 percentage of participants |
| Placebo | Percentage of Participants Achieving Eczema Area and Severity Index Response of 100% Improvement (EASI-100) From Baseline at Weeks 2, 4, 8 and 12 | Week 4 | 0 percentage of participants |
| Placebo | Percentage of Participants Achieving Eczema Area and Severity Index Response of 100% Improvement (EASI-100) From Baseline at Weeks 2, 4, 8 and 12 | Week 8 | 0 percentage of participants |
| Placebo | Percentage of Participants Achieving Eczema Area and Severity Index Response of 100% Improvement (EASI-100) From Baseline at Weeks 2, 4, 8 and 12 | Week 2 | 0 percentage of participants |
Comparison: Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.95% CI: [-3.7, 3.7]
Comparison: Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.326195% CI: [-2.8, 5.3]Cochran-Mantel-Haenszel
Comparison: Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.320795% CI: [-2.7, 5.3]Cochran-Mantel-Haenszel
Comparison: Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.08195% CI: [-0.8, 8.5]Cochran-Mantel-Haenszel
Comparison: Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.320795% CI: [-2.7, 5.2]Cochran-Mantel-Haenszel
Comparison: Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.08195% CI: [-0.7, 8.4]Cochran-Mantel-Haenszel
Comparison: Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.041995% CI: [0.3, 10.1]Cochran-Mantel-Haenszel
Comparison: Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.01895% CI: [1.8, 12.2]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving Eczema Area and Severity Index Response of >=50% Improvement (EASI-50) From Baseline at Weeks 2, 4, 8 and 12
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.
Time frame: Baseline, Weeks 2, 4, 8, and 12
Population: Full analysis set included all randomized participants who received at least 1 dose of study medication. Here, Number Analyzed signifies number of participants evaluable at the specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04965842 100 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=50% Improvement (EASI-50) From Baseline at Weeks 2, 4, 8 and 12 | Week 2 | 35.7 percentage of participants |
| PF-04965842 100 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=50% Improvement (EASI-50) From Baseline at Weeks 2, 4, 8 and 12 | Week 4 | 58.7 percentage of participants |
| PF-04965842 100 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=50% Improvement (EASI-50) From Baseline at Weeks 2, 4, 8 and 12 | Week 8 | 66.2 percentage of participants |
| PF-04965842 100 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=50% Improvement (EASI-50) From Baseline at Weeks 2, 4, 8 and 12 | Week 12 | 68.4 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=50% Improvement (EASI-50) From Baseline at Weeks 2, 4, 8 and 12 | Week 12 | 79.9 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=50% Improvement (EASI-50) From Baseline at Weeks 2, 4, 8 and 12 | Week 2 | 55.3 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=50% Improvement (EASI-50) From Baseline at Weeks 2, 4, 8 and 12 | Week 8 | 82.5 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=50% Improvement (EASI-50) From Baseline at Weeks 2, 4, 8 and 12 | Week 4 | 78.4 percentage of participants |
| Placebo | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=50% Improvement (EASI-50) From Baseline at Weeks 2, 4, 8 and 12 | Week 12 | 19.5 percentage of participants |
| Placebo | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=50% Improvement (EASI-50) From Baseline at Weeks 2, 4, 8 and 12 | Week 4 | 28.6 percentage of participants |
| Placebo | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=50% Improvement (EASI-50) From Baseline at Weeks 2, 4, 8 and 12 | Week 8 | 34.6 percentage of participants |
| Placebo | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=50% Improvement (EASI-50) From Baseline at Weeks 2, 4, 8 and 12 | Week 2 | 10.5 percentage of participants |
Comparison: Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [14.8, 35.2]Cochran-Mantel-Haenszel
Comparison: Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [33.9, 54.6]Cochran-Mantel-Haenszel
Comparison: Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [17.5, 42.8]Cochran-Mantel-Haenszel
Comparison: Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [37.8, 61.7]Cochran-Mantel-Haenszel
Comparison: Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [18.8, 44.3]Cochran-Mantel-Haenszel
Comparison: Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [35.7, 59.6]Cochran-Mantel-Haenszel
Comparison: Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [37.2, 60.1]Cochran-Mantel-Haenszel
Comparison: Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [49.1, 71]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving Eczema Area and Severity Index Response of >=75% Improvement (EASI-75) From Baseline at Weeks 2, 4 and 8
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.
Time frame: Baseline, Weeks 2, 4, and 8
Population: Full analysis set included all randomized participants who received at least 1 dose of study medication. Here, Number Analyzed signifies the number of participants evaluable at specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04965842 100 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=75% Improvement (EASI-75) From Baseline at Weeks 2, 4 and 8 | Week 4 | 26.5 percentage of participants |
| PF-04965842 100 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=75% Improvement (EASI-75) From Baseline at Weeks 2, 4 and 8 | Week 2 | 10.2 percentage of participants |
| PF-04965842 100 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=75% Improvement (EASI-75) From Baseline at Weeks 2, 4 and 8 | Week 8 | 43.3 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=75% Improvement (EASI-75) From Baseline at Weeks 2, 4 and 8 | Week 4 | 51.0 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=75% Improvement (EASI-75) From Baseline at Weeks 2, 4 and 8 | Week 2 | 24.3 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=75% Improvement (EASI-75) From Baseline at Weeks 2, 4 and 8 | Week 8 | 60.4 percentage of participants |
| Placebo | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=75% Improvement (EASI-75) From Baseline at Weeks 2, 4 and 8 | Week 2 | 1.3 percentage of participants |
| Placebo | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=75% Improvement (EASI-75) From Baseline at Weeks 2, 4 and 8 | Week 8 | 12.8 percentage of participants |
| Placebo | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=75% Improvement (EASI-75) From Baseline at Weeks 2, 4 and 8 | Week 4 | 6.5 percentage of participants |
Comparison: Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.01595% CI: [2.8, 14.9]Cochran-Mantel-Haenszel
Comparison: Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [15, 30.3]Cochran-Mantel-Haenszel
Comparison: Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.000495% CI: [10.9, 29]Cochran-Mantel-Haenszel
Comparison: Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [34.8, 53.8]Cochran-Mantel-Haenszel
Comparison: Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [19.7, 41.2]Cochran-Mantel-Haenszel
Comparison: Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [36.8, 58]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving Eczema Area and Severity Index Response of >=90% Improvement (EASI-90) From Baseline at Weeks 2, 4, 8 and 12
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.
Time frame: Baseline, Weeks 2, 4, 8, and 12
Population: Full analysis set included all randomized participants who received at least 1 dose of study medication. Here, Number Analyzed signifies number of participants evaluable at the specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04965842 100 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=90% Improvement (EASI-90) From Baseline at Weeks 2, 4, 8 and 12 | Week 2 | 2.5 percentage of participants |
| PF-04965842 100 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=90% Improvement (EASI-90) From Baseline at Weeks 2, 4, 8 and 12 | Week 4 | 9.7 percentage of participants |
| PF-04965842 100 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=90% Improvement (EASI-90) From Baseline at Weeks 2, 4, 8 and 12 | Week 8 | 17.2 percentage of participants |
| PF-04965842 100 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=90% Improvement (EASI-90) From Baseline at Weeks 2, 4, 8 and 12 | Week 12 | 23.9 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=90% Improvement (EASI-90) From Baseline at Weeks 2, 4, 8 and 12 | Week 12 | 37.7 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=90% Improvement (EASI-90) From Baseline at Weeks 2, 4, 8 and 12 | Week 2 | 9.2 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=90% Improvement (EASI-90) From Baseline at Weeks 2, 4, 8 and 12 | Week 8 | 34.4 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=90% Improvement (EASI-90) From Baseline at Weeks 2, 4, 8 and 12 | Week 4 | 22.9 percentage of participants |
| Placebo | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=90% Improvement (EASI-90) From Baseline at Weeks 2, 4, 8 and 12 | Week 12 | 3.9 percentage of participants |
| Placebo | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=90% Improvement (EASI-90) From Baseline at Weeks 2, 4, 8 and 12 | Week 4 | 0 percentage of participants |
| Placebo | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=90% Improvement (EASI-90) From Baseline at Weeks 2, 4, 8 and 12 | Week 8 | 2.6 percentage of participants |
| Placebo | Percentage of Participants Achieving Eczema Area and Severity Index Response of >=90% Improvement (EASI-90) From Baseline at Weeks 2, 4, 8 and 12 | Week 2 | 0 percentage of participants |
Comparison: Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.162395% CI: [-1.7, 6.8]Cochran-Mantel-Haenszel
Comparison: Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.00795% CI: [3.4, 14.7]Cochran-Mantel-Haenszel
Comparison: Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.004995% CI: [4, 15.4]Cochran-Mantel-Haenszel
Comparison: Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [15.5, 30.2]Cochran-Mantel-Haenszel
Comparison: Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.001395% CI: [7.2, 22]Cochran-Mantel-Haenszel
Comparison: Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [23.1, 40.1]Cochran-Mantel-Haenszel
Comparison: Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.000195% CI: [11.9, 28.3]Cochran-Mantel-Haenszel
Comparison: Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [24.6, 42.5]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving IGA Response of Clear (0) or Almost Clear (1) and >=2 Points Improvement From Baseline at Weeks 2, 4 and 8
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.
Time frame: Baseline, Weeks 2, 4, and 8
Population: Full analysis set included all randomized participants who received at least 1 dose of study medication. Here, Number Analyzed signifies the number of participants evaluable at specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04965842 100 mg | Percentage of Participants Achieving IGA Response of Clear (0) or Almost Clear (1) and >=2 Points Improvement From Baseline at Weeks 2, 4 and 8 | Week 4 | 14.2 percentage of participants |
| PF-04965842 100 mg | Percentage of Participants Achieving IGA Response of Clear (0) or Almost Clear (1) and >=2 Points Improvement From Baseline at Weeks 2, 4 and 8 | Week 2 | 5.1 percentage of participants |
| PF-04965842 100 mg | Percentage of Participants Achieving IGA Response of Clear (0) or Almost Clear (1) and >=2 Points Improvement From Baseline at Weeks 2, 4 and 8 | Week 8 | 22.3 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving IGA Response of Clear (0) or Almost Clear (1) and >=2 Points Improvement From Baseline at Weeks 2, 4 and 8 | Week 4 | 33.3 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving IGA Response of Clear (0) or Almost Clear (1) and >=2 Points Improvement From Baseline at Weeks 2, 4 and 8 | Week 2 | 14.5 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving IGA Response of Clear (0) or Almost Clear (1) and >=2 Points Improvement From Baseline at Weeks 2, 4 and 8 | Week 8 | 37.7 percentage of participants |
| Placebo | Percentage of Participants Achieving IGA Response of Clear (0) or Almost Clear (1) and >=2 Points Improvement From Baseline at Weeks 2, 4 and 8 | Week 2 | 0 percentage of participants |
| Placebo | Percentage of Participants Achieving IGA Response of Clear (0) or Almost Clear (1) and >=2 Points Improvement From Baseline at Weeks 2, 4 and 8 | Week 8 | 10.3 percentage of participants |
| Placebo | Percentage of Participants Achieving IGA Response of Clear (0) or Almost Clear (1) and >=2 Points Improvement From Baseline at Weeks 2, 4 and 8 | Week 4 | 1.3 percentage of participants |
Comparison: Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.045995% CI: [0.2, 10]Cochran-Mantel-Haenszel
Comparison: Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.000595% CI: [7.8, 20.5]Cochran-Mantel-Haenszel
Comparison: Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.001995% CI: [6.3, 19.4]Cochran-Mantel-Haenszel
Comparison: Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [23.6, 39.9]Cochran-Mantel-Haenszel
Comparison: Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.024695% CI: [2.4, 21.4]Cochran-Mantel-Haenszel
Comparison: Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [17, 36.9]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of Clear (0) at Week 2, 4, 8 and 12
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 soles, palms and scalp.
Time frame: Weeks 2, 4, 8 and 12
Population: Full analysis set included all randomized participants who received at least 1 dose of study medication. Here, Number Analyzed signifies number of participants evaluable at the specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04965842 100 mg | Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of Clear (0) at Week 2, 4, 8 and 12 | Week 2 | 0 percentage of participants |
| PF-04965842 100 mg | Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of Clear (0) at Week 2, 4, 8 and 12 | Week 4 | 1.9 percentage of participants |
| PF-04965842 100 mg | Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of Clear (0) at Week 2, 4, 8 and 12 | Week 8 | 1.3 percentage of participants |
| PF-04965842 100 mg | Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of Clear (0) at Week 2, 4, 8 and 12 | Week 12 | 5.2 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of Clear (0) at Week 2, 4, 8 and 12 | Week 12 | 6.5 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of Clear (0) at Week 2, 4, 8 and 12 | Week 2 | 2.0 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of Clear (0) at Week 2, 4, 8 and 12 | Week 8 | 4.5 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of Clear (0) at Week 2, 4, 8 and 12 | Week 4 | 4.6 percentage of participants |
| Placebo | Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of Clear (0) at Week 2, 4, 8 and 12 | Week 12 | 0 percentage of participants |
| Placebo | Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of Clear (0) at Week 2, 4, 8 and 12 | Week 4 | 0 percentage of participants |
| Placebo | Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of Clear (0) at Week 2, 4, 8 and 12 | Week 8 | 0 percentage of participants |
| Placebo | Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of Clear (0) at Week 2, 4, 8 and 12 | Week 2 | 0 percentage of participants |
Comparison: Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.95% CI: [-3.7, 3.7]
Comparison: Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.226295% CI: [-2.2, 6.1]Cochran-Mantel-Haenszel
Comparison: Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.222395% CI: [-2.2, 6.1]Cochran-Mantel-Haenszel
Comparison: Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.059795% CI: [-0.2, 9.2]Cochran-Mantel-Haenszel
Comparison: Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.320795% CI: [-2.7, 5.2]Cochran-Mantel-Haenszel
Comparison: Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.058695% CI: [-0.2, 9.2]Cochran-Mantel-Haenszel
Comparison: Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.041995% CI: [0.3, 10.1]Cochran-Mantel-Haenszel
Comparison: Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.024495% CI: [1.2, 11.4]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=50% Improvement From Baseline at Week 2, 4, 8 and 12
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.
Time frame: Baseline, Weeks 2, 4, 8, and 12
Population: Full analysis set included all randomized participants who received at least 1 dose of study medication. Here, Number Analyzed signifies number of participants evaluable at the specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04965842 100 mg | Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=50% Improvement From Baseline at Week 2, 4, 8 and 12 | Week 2 | 12.7 percentage of participants |
| PF-04965842 100 mg | Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=50% Improvement From Baseline at Week 2, 4, 8 and 12 | Week 4 | 36.1 percentage of participants |
| PF-04965842 100 mg | Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=50% Improvement From Baseline at Week 2, 4, 8 and 12 | Week 8 | 43.3 percentage of participants |
| PF-04965842 100 mg | Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=50% Improvement From Baseline at Week 2, 4, 8 and 12 | Week 12 | 49.0 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=50% Improvement From Baseline at Week 2, 4, 8 and 12 | Week 12 | 62.6 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=50% Improvement From Baseline at Week 2, 4, 8 and 12 | Week 2 | 32.9 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=50% Improvement From Baseline at Week 2, 4, 8 and 12 | Week 8 | 61.7 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=50% Improvement From Baseline at Week 2, 4, 8 and 12 | Week 4 | 60.8 percentage of participants |
| Placebo | Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=50% Improvement From Baseline at Week 2, 4, 8 and 12 | Week 12 | 12.8 percentage of participants |
| Placebo | Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=50% Improvement From Baseline at Week 2, 4, 8 and 12 | Week 4 | 7.8 percentage of participants |
| Placebo | Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=50% Improvement From Baseline at Week 2, 4, 8 and 12 | Week 8 | 15.4 percentage of participants |
| Placebo | Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=50% Improvement From Baseline at Week 2, 4, 8 and 12 | Week 2 | 0 percentage of participants |
Comparison: Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.001195% CI: [6.5, 18.9]Cochran-Mantel-Haenszel
Comparison: Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [24.6, 40.6]Cochran-Mantel-Haenszel
Comparison: Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [18.5, 38.2]Cochran-Mantel-Haenszel
Comparison: Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [43.2, 62.5]Cochran-Mantel-Haenszel
Comparison: Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [17, 39]Cochran-Mantel-Haenszel
Comparison: Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [35.2, 57.1]Cochran-Mantel-Haenszel
Comparison: Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [25.4, 47.1]Cochran-Mantel-Haenszel
Comparison: Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [38.9, 60.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=75% Improvement From Baseline at Week 2, 4, 8 and 12
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.
Time frame: Baseline, Weeks 2, 4, 8, and 12
Population: Full analysis set included all randomized participants who received at least 1 dose of study medication. Here, Number Analyzed signifies number of participants evaluable at the specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04965842 100 mg | Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=75% Improvement From Baseline at Week 2, 4, 8 and 12 | Week 2 | 1.9 percentage of participants |
| PF-04965842 100 mg | Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=75% Improvement From Baseline at Week 2, 4, 8 and 12 | Week 4 | 7.1 percentage of participants |
| PF-04965842 100 mg | Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=75% Improvement From Baseline at Week 2, 4, 8 and 12 | Week 8 | 11.5 percentage of participants |
| PF-04965842 100 mg | Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=75% Improvement From Baseline at Week 2, 4, 8 and 12 | Week 12 | 18.7 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=75% Improvement From Baseline at Week 2, 4, 8 and 12 | Week 12 | 30.3 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=75% Improvement From Baseline at Week 2, 4, 8 and 12 | Week 2 | 5.3 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=75% Improvement From Baseline at Week 2, 4, 8 and 12 | Week 8 | 26.0 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=75% Improvement From Baseline at Week 2, 4, 8 and 12 | Week 4 | 17.6 percentage of participants |
| Placebo | Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=75% Improvement From Baseline at Week 2, 4, 8 and 12 | Week 12 | 2.6 percentage of participants |
| Placebo | Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=75% Improvement From Baseline at Week 2, 4, 8 and 12 | Week 4 | 0 percentage of participants |
| Placebo | Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=75% Improvement From Baseline at Week 2, 4, 8 and 12 | Week 8 | 0 percentage of participants |
| Placebo | Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) Response >=75% Improvement From Baseline at Week 2, 4, 8 and 12 | Week 2 | 0 percentage of participants |
Comparison: Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.226195% CI: [-2.2, 6]Cochran-Mantel-Haenszel
Comparison: Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.045195% CI: [0.3, 10]Cochran-Mantel-Haenszel
Comparison: Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.017195% CI: [1.8, 12.3]Cochran-Mantel-Haenszel
Comparison: Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [10.9, 24.5]Cochran-Mantel-Haenszel
Comparison: Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.001895% CI: [5.5, 17.5]Cochran-Mantel-Haenszel
Comparison: Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [18.3, 33.1]Cochran-Mantel-Haenszel
Comparison: Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.000595% CI: [8.8, 23.6]Cochran-Mantel-Haenszel
Comparison: Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [19.3, 35.8]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved at Least 4-Points Improvement From Baseline in the Numerical Rating Scale (NRS) for Severity of Pruritus at Weeks 2, 4, 8 and 12
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.
Time frame: Baseline, Weeks 2, 4, 8 and 12
Population: Full analysis set included all randomized participants who received at least 1 dose of study medication. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04965842 100 mg | Percentage of Participants Who Achieved at Least 4-Points Improvement From Baseline in the Numerical Rating Scale (NRS) for Severity of Pruritus at Weeks 2, 4, 8 and 12 | Week 2 | 23.1 percentage of participants |
| PF-04965842 100 mg | Percentage of Participants Who Achieved at Least 4-Points Improvement From Baseline in the Numerical Rating Scale (NRS) for Severity of Pruritus at Weeks 2, 4, 8 and 12 | Week 4 | 31.4 percentage of participants |
| PF-04965842 100 mg | Percentage of Participants Who Achieved at Least 4-Points Improvement From Baseline in the Numerical Rating Scale (NRS) for Severity of Pruritus at Weeks 2, 4, 8 and 12 | Week 8 | 39.1 percentage of participants |
| PF-04965842 100 mg | Percentage of Participants Who Achieved at Least 4-Points Improvement From Baseline in the Numerical Rating Scale (NRS) for Severity of Pruritus at Weeks 2, 4, 8 and 12 | Week 12 | 39.7 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Who Achieved at Least 4-Points Improvement From Baseline in the Numerical Rating Scale (NRS) for Severity of Pruritus at Weeks 2, 4, 8 and 12 | Week 12 | 49.0 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Who Achieved at Least 4-Points Improvement From Baseline in the Numerical Rating Scale (NRS) for Severity of Pruritus at Weeks 2, 4, 8 and 12 | Week 2 | 35.3 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Who Achieved at Least 4-Points Improvement From Baseline in the Numerical Rating Scale (NRS) for Severity of Pruritus at Weeks 2, 4, 8 and 12 | Week 8 | 51.6 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants Who Achieved at Least 4-Points Improvement From Baseline in the Numerical Rating Scale (NRS) for Severity of Pruritus at Weeks 2, 4, 8 and 12 | Week 4 | 50.3 percentage of participants |
| Placebo | Percentage of Participants Who Achieved at Least 4-Points Improvement From Baseline in the Numerical Rating Scale (NRS) for Severity of Pruritus at Weeks 2, 4, 8 and 12 | Week 12 | 10.5 percentage of participants |
| Placebo | Percentage of Participants Who Achieved at Least 4-Points Improvement From Baseline in the Numerical Rating Scale (NRS) for Severity of Pruritus at Weeks 2, 4, 8 and 12 | Week 4 | 3.9 percentage of participants |
| Placebo | Percentage of Participants Who Achieved at Least 4-Points Improvement From Baseline in the Numerical Rating Scale (NRS) for Severity of Pruritus at Weeks 2, 4, 8 and 12 | Week 8 | 11.8 percentage of participants |
| Placebo | Percentage of Participants Who Achieved at Least 4-Points Improvement From Baseline in the Numerical Rating Scale (NRS) for Severity of Pruritus at Weeks 2, 4, 8 and 12 | Week 2 | 3.9 percentage of participants |
Comparison: Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.000295% CI: [11, 27.4]Cochran-Mantel-Haenszel
Comparison: Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [22.3, 40.2]Cochran-Mantel-Haenszel
Comparison: Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [18.9, 36.2]Cochran-Mantel-Haenszel
Comparison: Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [37.2, 55.7]Cochran-Mantel-Haenszel
Comparison: Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [16.8, 38]Cochran-Mantel-Haenszel
Comparison: Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [28.9, 50.6]Cochran-Mantel-Haenszel
Comparison: Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [18.9, 39.6]Cochran-Mantel-Haenszel
Comparison: Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [28.1, 49.1]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Percentage Body Surface Area (%BSA) (From EASI) < 5% at Weeks 2, 4, 8 and 12
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.
Time frame: Weeks 2, 4, 8, and 12
Population: Full analysis set included all randomized participants who received at least 1 dose of study medication. Here, Number Analyzed signifies number of participants evaluable at the specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04965842 100 mg | Percentage of Participants With Percentage Body Surface Area (%BSA) (From EASI) < 5% at Weeks 2, 4, 8 and 12 | Week 2 | 1.9 percentage of participants |
| PF-04965842 100 mg | Percentage of Participants With Percentage Body Surface Area (%BSA) (From EASI) < 5% at Weeks 2, 4, 8 and 12 | Week 4 | 6.5 percentage of participants |
| PF-04965842 100 mg | Percentage of Participants With Percentage Body Surface Area (%BSA) (From EASI) < 5% at Weeks 2, 4, 8 and 12 | Week 8 | 15.9 percentage of participants |
| PF-04965842 100 mg | Percentage of Participants With Percentage Body Surface Area (%BSA) (From EASI) < 5% at Weeks 2, 4, 8 and 12 | Week 12 | 22.6 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants With Percentage Body Surface Area (%BSA) (From EASI) < 5% at Weeks 2, 4, 8 and 12 | Week 12 | 34.4 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants With Percentage Body Surface Area (%BSA) (From EASI) < 5% at Weeks 2, 4, 8 and 12 | Week 2 | 5.9 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants With Percentage Body Surface Area (%BSA) (From EASI) < 5% at Weeks 2, 4, 8 and 12 | Week 8 | 27.3 percentage of participants |
| PF-04965842 200 mg | Percentage of Participants With Percentage Body Surface Area (%BSA) (From EASI) < 5% at Weeks 2, 4, 8 and 12 | Week 4 | 17.0 percentage of participants |
| Placebo | Percentage of Participants With Percentage Body Surface Area (%BSA) (From EASI) < 5% at Weeks 2, 4, 8 and 12 | Week 12 | 3.9 percentage of participants |
| Placebo | Percentage of Participants With Percentage Body Surface Area (%BSA) (From EASI) < 5% at Weeks 2, 4, 8 and 12 | Week 4 | 0 percentage of participants |
| Placebo | Percentage of Participants With Percentage Body Surface Area (%BSA) (From EASI) < 5% at Weeks 2, 4, 8 and 12 | Week 8 | 1.3 percentage of participants |
| Placebo | Percentage of Participants With Percentage Body Surface Area (%BSA) (From EASI) < 5% at Weeks 2, 4, 8 and 12 | Week 2 | 0 percentage of participants |
Comparison: Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.235395% CI: [-2.2, 6]Cochran-Mantel-Haenszel
Comparison: Week 2: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.033295% CI: [0.8, 10.8]Cochran-Mantel-Haenszel
Comparison: Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.022795% CI: [1.4, 11.6]Cochran-Mantel-Haenszel
Comparison: Week 4: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.000195% CI: [10.1, 23.5]Cochran-Mantel-Haenszel
Comparison: Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.000895% CI: [7.7, 21.3]Cochran-Mantel-Haenszel
Comparison: Week 8: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [18.1, 33.4]Cochran-Mantel-Haenszel
Comparison: Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: 0.000395% CI: [10.5, 26.5]Cochran-Mantel-Haenszel
Comparison: Week 12: The estimate and CI for difference were calculated based on the weighted average of difference for each randomization stratum using the normal approximation of binomial proportions.p-value: <0.000195% CI: [21.4, 39]Cochran-Mantel-Haenszel
Secondary
Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 2, 4, 8 and 12
EASI evaluates severity of participant's 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.
Time frame: Baseline, Weeks 2, 4, 8, and 12
Population: Full analysis set included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| PF-04965842 100 mg | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 2, 4, 8 and 12 | Change at Week 2 | -39.2 percent change |
| PF-04965842 100 mg | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 2, 4, 8 and 12 | Change at Week 4 | -54.3 percent change |
| PF-04965842 100 mg | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 2, 4, 8 and 12 | Change at Week 8 | -59.5 percent change |
| PF-04965842 100 mg | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 2, 4, 8 and 12 | Change at Week 12 | -60.0 percent change |
| PF-04965842 200 mg | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 2, 4, 8 and 12 | Change at Week 12 | -73.3 percent change |
| PF-04965842 200 mg | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 2, 4, 8 and 12 | Change at Week 2 | -51.3 percent change |
| PF-04965842 200 mg | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 2, 4, 8 and 12 | Change at Week 8 | -73.2 percent change |
| PF-04965842 200 mg | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 2, 4, 8 and 12 | Change at Week 4 | -69.0 percent change |
| Placebo | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 2, 4, 8 and 12 | Change at Week 12 | -28.6 percent change |
| Placebo | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 2, 4, 8 and 12 | Change at Week 4 | -24.4 percent change |
| Placebo | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 2, 4, 8 and 12 | Change at Week 8 | -33.0 percent change |
| Placebo | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 2, 4, 8 and 12 | Change at Week 2 | -9.0 percent change |
Comparison: Change at Week 2: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.p-value: <0.000195% CI: [-38.1, -22.3]Mixed Models Analysis
Comparison: Change at Week 2: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.p-value: <0.000195% CI: [-50.3, -34.4]Mixed Models Analysis
Comparison: Change at Week 4: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.p-value: <0.000195% CI: [-38.1, -21.7]Mixed Models Analysis
Comparison: Change at Week 4: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.p-value: <0.000195% CI: [-52.8, -36.3]Mixed Models Analysis
Comparison: Change at Week 8: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.p-value: <0.000195% CI: [-36.2, -16.7]Mixed Models Analysis
Comparison: Change at Week 8: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.p-value: <0.000195% CI: [-50, -30.4]Mixed Models Analysis
Comparison: Change at Week 12: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.p-value: <0.000195% CI: [-43.1, -19.7]Mixed Models Analysis
Comparison: Change at Week 12: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.p-value: <0.000195% CI: [-56.4, -33]Mixed Models Analysis
Secondary
Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Total Score at Week 2, 4, 8 and 12
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.
Time frame: Baseline, Weeks 2, 4, 8, and 12
Population: Full analysis set included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| PF-04965842 100 mg | Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Total Score at Week 2, 4, 8 and 12 | Change at Week 2 | -27.2 percent change |
| PF-04965842 100 mg | Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Total Score at Week 2, 4, 8 and 12 | Change at Week 4 | -38.9 percent change |
| PF-04965842 100 mg | Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Total Score at Week 2, 4, 8 and 12 | Change at Week 8 | -42.6 percent change |
| PF-04965842 100 mg | Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Total Score at Week 2, 4, 8 and 12 | Change at Week 12 | -45.8 percent change |
| PF-04965842 200 mg | Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Total Score at Week 2, 4, 8 and 12 | Change at Week 12 | -56.2 percent change |
| PF-04965842 200 mg | Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Total Score at Week 2, 4, 8 and 12 | Change at Week 2 | -38.5 percent change |
| PF-04965842 200 mg | Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Total Score at Week 2, 4, 8 and 12 | Change at Week 8 | -56.7 percent change |
| PF-04965842 200 mg | Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Total Score at Week 2, 4, 8 and 12 | Change at Week 4 | -53.1 percent change |
| Placebo | Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Total Score at Week 2, 4, 8 and 12 | Change at Week 12 | -22.7 percent change |
| Placebo | Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Total Score at Week 2, 4, 8 and 12 | Change at Week 4 | -17.2 percent change |
| Placebo | Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Total Score at Week 2, 4, 8 and 12 | Change at Week 8 | -23.1 percent change |
| Placebo | Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Total Score at Week 2, 4, 8 and 12 | Change at Week 2 | -6.3 percent change |
Comparison: Change at Week 2: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.p-value: <0.000195% CI: [-26.6, -15.1]Mixed Models Analysis
Comparison: Change at Week 2: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.p-value: <0.000195% CI: [-37.9, -26.4]Mixed Models Analysis
Comparison: Change at Week 4: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.p-value: <0.000195% CI: [-28.1, -15.2]Mixed Models Analysis
Comparison: Change at Week 4: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.p-value: <0.000195% CI: [-42.3, -29.4]Mixed Models Analysis
Comparison: Change at Week 8: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.p-value: <0.000195% CI: [-26.8, -12.1]Mixed Models Analysis
Comparison: Change at Week 8: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.p-value: <0.000195% CI: [-41, -26.3]Mixed Models Analysis
Comparison: Change at Week 12: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.p-value: <0.000195% CI: [-32.3, -13.9]Mixed Models Analysis
Comparison: Change at Week 12: MMRM contained fixed factors of treatment, visit, treatment by visit interaction, randomization strata (baseline disease severity and age category) and baseline value and used an unstructured covariance matrix.p-value: <0.000195% CI: [-42.6, -24.3]Mixed Models Analysis
Secondary
Time to Achieve >=4 Points Improvement From Baseline in Numerical Rating Scale (NRS) for Severity of Pruritus
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.
Time frame: Baseline up to Day 15
Population: Full analysis set included all randomized participants who received at least 1 dose of study medication. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PF-04965842 100 mg | Time to Achieve >=4 Points Improvement From Baseline in Numerical Rating Scale (NRS) for Severity of Pruritus | 58.0 days |
| PF-04965842 200 mg | Time to Achieve >=4 Points Improvement From Baseline in Numerical Rating Scale (NRS) for Severity of Pruritus | 29.0 days |
| Placebo | Time to Achieve >=4 Points Improvement From Baseline in Numerical Rating Scale (NRS) for Severity of Pruritus | 112.0 days |