Dose Ranging Study to Assess Efficacy, Safety, Tolerability and Pharmacokinetics of PF-06700841 Topical Cream in Participants With Mild or Moderate Atopic Dermatitis

Phase 2

Completed

Conditions: Atopic Dermatitis

Interventions: Drug: PF-06700841
Drug: Vehicle (Placebo)

Registration Number: NCT03903822

Lead Sponsor: Pfizer

Brief Summary: This study is being conducted to provide data on efficacy, safety, tolerability and PK of multiple topical formulation concentrations of PF-06700841 topical cream in the treatment of mild to moderate atopic dermatitis (AD). The study is intended to enable selection of the dose and dosing regimen (once daily \[QD\] vs twice daily \[BID\] application) for the future clinical development of topical PF-06700841.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 292

Inclusion Criteria

Clinical diagnosis of Atopic Dermatitis for at least 3 months
Investigator's Global Assessment (IGA) Score of 2 or 3
Eczema Area Severity Index (EASI) score of 3-21
Body Surface Area (BSA) of 2-20%
Peak pruritus-Numerical Rating Scale (PPNRS) of Grade 2 or more

Exclusion Criteria

Other forms of dermatological diseases (other than atopic dermatitis)
Fitzpatrick skin type score greater than 5
Clinically significant abnormal ECG, vital signs, and laboratory values
Infection with HBV, HCV, herpes zoster or tuberculosis

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PF-06700841 3% cream QD	PF-06700841	PF-06700841 3% cream applied once daily (QD)
PF-06700841 1% cream BID	PF-06700841	PF-06700841 1% cream applied twice daily (BID)
PF-06700841 0.3% cream BID	PF-06700841	PF-06700841 0.3% cream applied twice daily (BID)
Vehicle cream QD	Vehicle (Placebo)	Vehicle cream applied once daily (QD)
Vehicle cream BID	Vehicle (Placebo)	Vehicle cream applied twice daily (BID)
PF-06700841 0.1% cream QD	PF-06700841	PF-06700841 0.1% cream applied once daily (QD)
PF-06700841 0.3% cream QD	PF-06700841	PF-06700841 0.3% cream applied once daily (QD)
PF-06700841 1% cream QD	PF-06700841	PF-06700841 1% cream applied once daily (QD)

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 6: Multiple Imputation	Baseline, Week 6	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 \[including buttocks\]) on4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in each 4 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
Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 6: Multiple Imputation	Baseline, Week 6	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 \[including buttocks\]) on4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in each 4 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 >=75% Improvement in Eczema Area and Severity Index Total Score (EASI-75) From Baseline at Weeks 1, 2, 3, 4 and 6: Non-responder Imputation	Baseline, Weeks 1, 2, 3, 4 and 6	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 \[including buttocks\]) on4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in each 4 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 Investigator's Global Assessment (IGA) Score Clear (0) or Almost Clear (1) and a Reduction From Baseline of Greater Than or Equal to ( >=2) Points at Week 6: Non-responder Imputation	Baseline, Week 6	IGA assesses severity of participant's AD on a 5 point scale. 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 and 4= severe AD with deep dark red lesions, severe erythema, papulation/induration, lichenification, excoriation and moderate to severe oozing/crusting. Higher scores indicating more severity of AD. Assessment excluded soles, palms and scalp.
Percentage of Participants Achieving >=2 Points Reduction in Peak Pruritus Numerical Rating Scale (PP-NRS) From Baseline at Weeks 1, 2, 3, 4 and 6: Non-responder Imputation	Baseline, Weeks 1, 2, 3, 4 and 6	The severity of itch (pruritus) due to AD was assessed using a horizontal NRS. Participants at specified time points were asked the following question: "How would you rate your itch due to AD at the worst moment during the previous 24 hours?" The scale ranged from 0-10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
Percentage of Participants Achieving >=4 Points Reduction in Peak Pruritus Numerical Rating Scale (PP-NRS) From Baseline at Weeks 1, 2, 3, 4, 6 and Follow-up Visit: Non-responder Imputation	Baseline, Weeks 1, 2, 3, 4, 6 and follow up visit (28 days after last dose of study drug = maximum up to Day 71)	The severity of itch (pruritus) due to AD was assessed using a horizontal NRS. Participants at specified time points were asked the following question: "How would you rate your itch due to AD at the worst moment during the previous 24 hours?" The scale ranged from 0-10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
Percent Change From Baseline in Affected Body Surface Area (BSA) at Weeks 1, 2, 3, 4, 6 and Follow-up Visit	Baseline, Weeks 1, 2, 3, 4, 6 and follow up visit (28 days after last dose of study drug = maximum up to Day 71)	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 full palmer hand) 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, ranged from 0 to 100%, with higher values representing greater severity of AD.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Baseline (Day 1) up to at least 28 days after last dose of study drug (approximately up to Week 11)	An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. Treatment-emergent were events between first dose of investigational product and up to 28 days after the last dose of investigational product that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and all non-SAEs.
Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings	Baseline up to Week 6	Clinically significant ECG criteria included PR interval: value greater than (\>) 280 millisecond (msec), percentage change greater than equal to (\>=) 25/50 percentage, QRS interval: value \>120 msec, percentage change \>= 50% and QT interval corrected using the Fridericia's formula (QTCF) value 450 msec and 30\<=change\<60.
Change From Baseline in Clinical Chemistry-Lactate Dehydrogenase Laboratory Values at Weeks 1, 2, 4, 6 and Follow-up Visit	Baseline, Weeks 1, 2, 4, 6 and follow up visit (28 days after last dose of study drug = maximum up to Day 71)
Change From Baseline in Hematology- Hemoglobin Laboratory Values at Weeks 1, 2, 4, 6 and Follow-up Visit	Baseline, Weeks 1, 2, 4, 6 and follow up visit (28 days after last dose of study drug = maximum up to Day 71)
Change From Baseline in Hematology - Hematocrit, Reticulocytes/Erythrocytes, Lymphocytes/Leukocytes, Neutrophils/Leukocytes, Basophils/Leukocytes, Eosinophils/Leukocytes and Monocytes/Leukocytes Laboratory Values at Weeks 1, 2, 4, 6 and Follow-up Visit	Baseline, Weeks 1, 2, 4, 6 and follow up visit (28 days after last dose of study drug = maximum up to Day 71)
Number of Participants With Laboratory Abnormalities	Baseline (Day 1) up to at least 28 days after last dose of study drug (approximately up to Week 11)	Hemoglobin (HGB),hematocrit,erythrocytes (ery.),HDL cholesterol (chl.)\<0.8\lower limit of normal(LLN);reticulocytes (ret.), ret./ery. (%)\<0.5\LLN,\>1.5\upper limit of normal (ULN);ery. mean corpuscular (EMC) volume,EMC HGB,EMC HGB concentration,potassium,chloride,calcium,bicarbonate\<0.9\LLN,\>1.1\ULN;platelets\<0.5\LLN,\>1.75\ULN;leukocytes (leu.),glucose\<0.6\LLN,\>1.5\ULN;lymphocytes (lym.), lym./leu.(%), neutrophils (neu.), neu./leu. (%), protein,albumin \<0.8\LLN,\>1.2\ULN;basophils (bas.), bas./leu.(%), eosinophils (eos.), eos./leu., monocytes (mon.), mon./leu.(%), urate \>1.2\ULN;bilirubin (total, direct, indirect)\>1.5\ULN;aspartate/alanine aminotransferase, gamma glutamyl transferase, lactate dehydrogenase, alkaline phosphatase\>3.0\ULN;urea nitrogen, creatinine, triglycerides, chl.\>1.3\ULN; sodium \<0.95\LLN,\>1.05\ULN; creatine kinase \>2.0\ULN;Urine: pH\<4.5,\>8;glucose, ketones, protein, HGB, urobilinogen,bilirubin,nitrite,leukocyte esterase\>=1;ery., leu.\>= 20;hyaline casts\>1;bacteria\>20.
Change From Baseline in Clinical Chemistry- Protein and Albumin Laboratory Values at Weeks 1, 2, 4, 6 and Follow-up Visit	Baseline, Weeks 1, 2, 4, 6 and follow up visit (28 days after last dose of study drug = maximum up to Day 71)
Change From Baseline in Clinical Chemistry- Sodium, Potassium, Chloride and Bicarbonate Laboratory Values at Weeks 1, 2, 4, 6 and Follow-up Visit	Baseline, Weeks 1, 2, 4, 6 and follow up visit (28 days after last dose of study drug = maximum up to Day 71)
Change From Baseline in Electrocardiogram (ECG) Parameter- Heart Rate at Weeks 2 and 6	Baseline, Weeks 2 and 6
Change From Baseline in PR, QRS, QTCF and QT Interval at Weeks 2 and 6	Baseline, Weeks 2 and 6
Change From Baseline in Vital Signs- Temperature at Weeks 2 and 6	Baseline, Weeks 2 and 6
Number of Participants With Pre-defined Criteria For Vital Signs	Baseline up to Week 6	Pre-defined criteria included: 1) Diastolic blood pressure (DBP), a) sitting DBP: change of \>= 20 millimeter of mercury (mmHg) increase, b) sitting DBP: change of \>=20mmHg decrease, c) supine DBP: less than (\<) 50 mmHg, d) supine DBP: change of \>= 20mmHg increase, e) supine DBP: change of \>= 20mmHg decrease; 2) Systolic blood pressure (SBP), a) sitting SBP: \<90 mmHg, b) sitting SBP: change of \>=30mmHg increase, c) sitting SBP: change of \>=30mmHg decrease, d) supine SBP: change of \>=30mmHg increase, e) supine SBP: change of \>=30mmHg decrease and f) Supine SBP: value \<90mmHg.
Change From Baseline in Hematology- Platelets, Leukocytes, Lymphocytes, Neutrophils, Basophils, Eosinophils and Monocytes Laboratory Values at Weeks 1, 2, 4, 6 and Follow-up Visit	Baseline, Weeks 1, 2, 4, 6 and follow up visit (28 days after last dose of study drug = maximum up to Day 71)
Change From Baseline in Lipids Profile Values at Week 6	Baseline, Week 6	Lipid parameters that were assessed: high density lipoprotein (HDL) cholesterol, triglycerides, cholesterol, low density lipoprotein (LDL) cholesterol.
Change From Baseline in Ratio of LDL Cholesterol to HDL Cholesterol Lipids Profile at Week 6	Baseline, Week 6	Mean change in total cholesterol/HDL cholesterol ratio was assessed and reported.
Change From Baseline in Hematology- Erythrocytes and Reticulocytes Laboratory Values at Weeks 1, 2, 4, 6 and Follow-up Visit	Baseline, Weeks 1, 2, 4, 6 and follow up visit (28 days after last dose of study drug = maximum up to Day 71)
Number of Participants With Each Severity Grade in Local Tolerability Assessments	Day 1 and any day on of Week 1, 2, 4, 6: pre dose (before application of IP) and post dose (after application of IP); Follow up visit (28 days after last dose of study drug = maximum up to Day 71) and Early termination (anytime within week 11)	Local tolerability skin assessments were performed by the investigator and graded based on severity from grade 0 to 4 as: grade 0=none (no evidence of local intolerance); grade 1=mild (minimal erythema and/or oedema, slight glazed appearance); grade 2= moderate (definite erythema and/or oedema with peeling and/or cracking but needs no adaptation of posology) grade 3=severe (erythema, oedema glazing with fissures, few vesicles or papules consider removing topical agent \[if still in place\]) and grade 4= very severe (strong reaction spreading beyond the treated area, bullous reaction, erosions: removal of topical agent \[if still in place\]). Higher grades indicated worsening of condition. Only those categories in which at least 1 participant had data were reported.
Change From Baseline in Clinical Chemistry- Urea Nitrogen, Urate, Calcium and Glucose Laboratory Values at Weeks 1, 2, 4, 6 and Follow-up Visit	Baseline, Weeks 1, 2, 4, 6 and follow up visit (28 days after last dose of study drug = maximum up to Day 71)
Change From Baseline in Vital Signs- Blood Pressure (BP) at Weeks 2 and 6	Baseline, Weeks 2 and 6	Blood pressure included supine and sitting systolic and diastolic BP.
Change From Baseline in Vital Signs- Pulse Rate at Weeks 2 and 6	Baseline, Weeks 2 and 6

Trial Locations

Locations (73): Center for Dermatology and Plastic Surgery
🇺🇸
Scottsdale, Arizona, United States
First OC Dermatology
🇺🇸
Fountain Valley, California, United States
California Dermatology & Clinical Research Institute
🇺🇸
Encinitas, California, United States
Beach Allergy and Asthma Specialty Group, A Medical Corporation
🇺🇸
Long Beach, California, United States
Clinical Science Institute
🇺🇸
Santa Monica, California, United States
Yolanda C. Holmes, MD
🇺🇸
Washington, District of Columbia, United States
Olympian Clinical Research
🇺🇸
Clearwater, Florida, United States
Accel Research Sites - DeLand Clinical Research Unit
🇺🇸
DeLand, Florida, United States
Jacksonville Center for Clinical Research
🇺🇸
Jacksonville, Florida, United States
Solutions Through Advanced Research, Inc
🇺🇸
Jacksonville, Florida, United States
Advanced Medical Research PC
🇺🇸
Sandy Springs, Georgia, United States
Sneeze, Wheeze & Itch Associates, LLC
🇺🇸
Normal, Illinois, United States
DS Research
🇺🇸
Louisville, Kentucky, United States
MediSearch Clinical Trials
🇺🇸
Saint Joseph, Missouri, United States
Vital Prospects Clinical Research Institute, PC
🇺🇸
Tulsa, Oklahoma, United States
Tanenbaum Dermatology Center
🇺🇸
Memphis, Tennessee, United States
studies in Dermatology, LLC
🇺🇸
Cypress, Texas, United States
Ventavia Research Group LLC
🇺🇸
Hurst, Texas, United States
Center for Clinical Studies, LTD. LLP
🇺🇸
Webster, Texas, United States
Summit Clinical Research, LLC
🇺🇸
Franklin, Virginia, United States
Virginia Dermatology and Skin Cancer Center
🇺🇸
Norfolk, Virginia, United States
Australian Clinical Research Network
🇦🇺
Maroubra, New South Wales, Australia
Center for Skin and Venereal Diseases EOOD - Sofia
🇧🇬
Sofia, Bulgaria
DCC Alexandrovska
🇧🇬
Sofia, Bulgaria
Emovis GmbH
🇩🇪
Berlin, Germany
Rothhaar Studien GmbH
🇩🇪
Berlin, Germany
ISA - Interdisciplinary Study Association GmbH
🇩🇪
Berlin, Germany
Klinikum Bielefeld gem.GmbH
🇩🇪
Bielefeld, Germany
Universitätsklinikum Bonn AöR
🇩🇪
Bonn, Germany
MENSINGDERMA research GmbH
🇩🇪
Hamburg, Germany
MVZ Alstermed GmbH
🇩🇪
Hamburg, Germany
Dermatologische Gemeinschaftspraxis
🇩🇪
Mahlow, Germany
Klinische Forschung Schwerin GmbH
🇩🇪
Schwerin, Germany
Shinjuku Minamiguchi Dermatology Skin Clinic
🇯🇵
Shinjuku-ku, Tokyo, Japan
Medical Corporation Jitai-kai Tachikawa Dermatology Clinic
🇯🇵
Tachikawa, Tokyo, Japan
Center for Clinical Studies, LTD.LLP
🇺🇸
Houston, Texas, United States
Wiseman Dermatology Research Inc.
🇨🇦
Winnipeg, Manitoba, Canada
Gentofte Hospital
🇩🇰
Hellerup, Denmark
Innovaderm Research Inc.
🇨🇦
Montreal, Quebec, Canada
Sinclair Dermatology
🇦🇺
East Melbourne, Victoria, Australia
Cabrini Hospital
🇦🇺
Malvern, Victoria, Australia
Center for Dermatology and Plastic Surgery/CCT
🇺🇸
Scottsdale, Arizona, United States
Dermatology Physicians of Connecticut
🇺🇸
Shelton, Connecticut, United States
Meridian Clinical Research, LLC
🇺🇸
Baton Rouge, Louisiana, United States
Health Concepts
🇺🇸
Rapid City, South Dakota, United States
Nakatsuhifuka Clinic
🇯🇵
Kita-ku, Osaka-shi, Osaka, Japan
New England Associates, LLC
🇺🇸
Bridgeport, Connecticut, United States
Diagnostic Consultative Center - Fokus-5 - Medical Establishment for Outpatient Care OOD
🇧🇬
Sofia, Bulgaria
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
🇭🇺
Szeged, Hungary
Clinical Neuroscience Solutions, Inc.
🇺🇸
Memphis, Tennessee, United States
Emeritus Research
🇦🇺
Camberwell, Victoria, Australia
Diex Recherche Sherbrooke Inc.
🇨🇦
Sherbrooke, Quebec, Canada
Debreceni Egyetem Klinikai Kozpont
🇭🇺
Debrecen, Hungary
Bacs-Kiskun Megyei Korhaz Szegedi Tudomanyegyetem Altalanos Orvostudomanyi Kar Oktato Korhaza
🇭🇺
Kecskemet, Hungary
Parkside Hiroo Ladies Clinic
🇯🇵
Minato-ku, Tokyo, Japan
Lynn Health Science Institute
🇺🇸
Oklahoma City, Oklahoma, United States
SKiN Health
🇨🇦
Cobourg, Ontario, Canada
Clinical Research Center of Alabama, LLC
🇺🇸
Birmingham, Alabama, United States
Universitätsklinikum Frankfurt
🇩🇪
Frankfurt, Germany
Precision Imaging
🇺🇸
Jacksonville, Florida, United States
Leavitt Medical Associates of Florida d/b/a Ameriderm Research
🇺🇸
Ormond Beach, Florida, United States
Semmelweis Egyetem Altalanos Orvostudomanyi Kar
🇭🇺
Budapest, Hungary
Tanpopo Skin Clinic
🇯🇵
Ota Ku, Tokyo, Japan
CRU Hungary Kft.
🇭🇺
Miskolc, Hungary
Kitago Dermatology Clinic
🇯🇵
Sapporo-shi, Hokkaido, Japan
WroMedica I. Bielicka, A. Strzalkowska s.c.
🇵🇱
Wroclaw, Poland
MTZ Clinical Research Sp. z o.o
🇵🇱
Warszawa, Poland
Health and Aesthetics Ltd
🇱🇻
Riga, Latvia
NASZ LEKARZ Przychodnie Medyczne
🇵🇱
Torun, Poland
Aesthetic dermatology clinic of Prof. J. Kisis
🇱🇻
Riga, Latvia
NZOZ Specjalistyczny Ośrodek Dermatologiczny DERMAL s.c.
🇵🇱
Bialystok, Poland
Outpatient Clinic of Ventspils
🇱🇻
Ventspils, Latvia
Dermatology Consulting Services, PLLC
🇺🇸
High Point, North Carolina, United States