Study Evaluating Efficacy and Safety of PF-04965842 in Subjects Aged 12 Years And Older With Moderate to Severe Atopic Dermatitis
- Conditions
- Dermatitis, Atopic
- Interventions
- Registration Number
- NCT03575871
- Lead Sponsor
- Pfizer
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 391
- 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
- Unwilling to discontinue current AD medications prior to the study or require treatment with prohibited medications during the study
- Prior treatment with JAK inhibitors
- Other active nonAD inflammatory skin diseases or conditions affecting skin
- Medical history including thrombocytopenia, coagulopathy or platelet dysfunction, Q wave interval abnormalities, current or history of certain infections, cancer, lymphoproliferative disorders and other medical conditions at the discretion of the investigator
- Pregnant or breastfeeding women, or women of childbearing potential who are unwilling to use contraception
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PF-04965842 200 mg PF-04965842 200 mg - PF-04965842 100 mg PF-04965842 100 mg - Placebo Placebo -
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 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.
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.
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 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.
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.
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.
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.
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.
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.
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) 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.
Trial Locations
- Locations (113)
Emmaus Research Center, Inc.
🇺🇸Anaheim, California, United States
Advanced Research Center, Inc. - Los Alamitos Site
🇺🇸Los Alamitos, California, United States
Peninsula Research Associates, Inc.
🇺🇸Rolling Hills Estates, California, United States
Clinical Science Institute
🇺🇸Santa Monica, California, United States
Asthma and Allergy Associates, PC
🇺🇸Colorado Springs, Colorado, United States
Colorado Springs Dermatology Clinic, PC
🇺🇸Colorado Springs, Colorado, United States
Olympian Clinical Research
🇺🇸Clearwater, Florida, United States
Clinical Neuroscience Solutions, Inc.
🇺🇸Memphis, Tennessee, United States
Precision Imaging
🇺🇸Jacksonville, Florida, United States
Solutions Through Advanced Research, Inc.
🇺🇸Jacksonville, Florida, United States
Scroll for more (103 remaining)Emmaus Research Center, Inc.🇺🇸Anaheim, California, United States