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

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ClinicalTrials.gov Identifier: NCT03903822
Recruitment Status : Completed
First Posted : April 4, 2019
Results First Posted : March 29, 2021
Last Update Posted : March 29, 2021
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE March 20, 2019
First Posted Date  ICMJE April 4, 2019
Results First Submitted Date  ICMJE January 20, 2021
Results First Posted Date  ICMJE March 29, 2021
Last Update Posted Date March 29, 2021
Actual Study Start Date  ICMJE May 13, 2019
Actual Primary Completion Date May 7, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 20, 2021)
Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 6: Multiple Imputation [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 2, 2019)
Percent change from baseline in Eczema Area and Severity Index at Week 6 [ Time Frame: Day 1 to Week 6 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 20, 2021)
  • 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 [ Time Frame: 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.
  • Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 6: Multiple Imputation [ Time Frame: 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 >=2 Points Reduction in Peak Pruritus Numerical Rating Scale (PP-NRS) From Baseline at Weeks 1, 2, 3, 4 and 6: Non-responder Imputation [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
  • 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 [ Time Frame: 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.
  • Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: 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 Pre-defined Criteria For Vital Signs [ Time Frame: 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.
  • Number of Participants With Laboratory Abnormalities [ Time Frame: 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.
  • Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings [ Time Frame: 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 [ Time Frame: 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- Protein and Albumin Laboratory Values at Weeks 1, 2, 4, 6 and Follow-up Visit [ Time Frame: 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- Urea Nitrogen, Urate, Calcium and Glucose Laboratory Values at Weeks 1, 2, 4, 6 and Follow-up Visit [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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- Erythrocytes and Reticulocytes Laboratory Values at Weeks 1, 2, 4, 6 and Follow-up Visit [ Time Frame: 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- Platelets, Leukocytes, Lymphocytes, Neutrophils, Basophils, Eosinophils and Monocytes Laboratory Values at Weeks 1, 2, 4, 6 and Follow-up Visit [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline, Week 6 ]
    Mean change in total cholesterol/HDL cholesterol ratio was assessed and reported.
  • Change From Baseline in Electrocardiogram (ECG) Parameter- Heart Rate at Weeks 2 and 6 [ Time Frame: Baseline, Weeks 2 and 6 ]
  • Change From Baseline in PR, QRS, QTCF and QT Interval at Weeks 2 and 6 [ Time Frame: Baseline, Weeks 2 and 6 ]
  • Change From Baseline in Vital Signs- Blood Pressure (BP) at Weeks 2 and 6 [ Time Frame: 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 [ Time Frame: Baseline, Weeks 2 and 6 ]
  • Change From Baseline in Vital Signs- Temperature at Weeks 2 and 6 [ Time Frame: Baseline, Weeks 2 and 6 ]
  • Number of Participants With Each Severity Grade in Local Tolerability Assessments [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 2, 2019)
  • Proportion of participants achieving Investigator's Global Assessment (IGA) score of clear (0) or almost clear (1) and a reduction of 2 or more points [ Time Frame: Week 6 ]
  • Change from baseline in EASI total score [ Time Frame: Day 1 to Week 6 ]
  • Proportion of participants achieving reduction in weekly averages of Peak Pruritus Numerical Scale (PP-NRS) by 2 or more more points [ Time Frame: Week 1, 2, 3, 4, 5, and 6 ]
  • Percent change in affected Body Surface Area (BSA) [ Time Frame: Day 1 to Week 6 ]
  • Proportion of participants achieving EASI-75 [ Time Frame: Day 1 to Week 6 ]
  • Incidence of treatment-emergent adverse events [ Time Frame: Day 1 to Week 6 ]
  • Number of participants with clinically significant change from baseline in clinical laboratory test results [ Time Frame: Day 1 to Week 6 ]
  • Number of participants with clinically significant changes from baseline in ECG parameters [ Time Frame: Day 1 to Week 6 ]
  • Number of participants with clinically significant change from baseline in vital signs [ Time Frame: Day 1 to Week 6 ]
  • Number of participants with each severity grade in local tolerability assessments [ Time Frame: Day 1 to Week 6 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose Ranging Study to Assess Efficacy, Safety, Tolerability and Pharmacokinetics of PF-06700841 Topical Cream in Participants With Mild or Moderate Atopic Dermatitis
Official Title  ICMJE A PHASE 2B, RANDOMIZED, DOUBLE BLIND, VEHICLE CONTROLLED, PARALLEL GROUP, DOSE RANGING STUDY TO ASSESS THE EFFICACY, SAFETY, TOLERABILITY AND PHARMACOKINETICS OF PF-06700841 CREAM APPLIED ONCE OR TWICE DAILY FOR 6 WEEKS IN PARTICIPANTS WITH MILD OR MODERATE ATOPIC DERMATITIS
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Atopic Dermatitis
Intervention  ICMJE
  • Drug: PF-06700841
    PF-06700841 topical cream
  • Drug: Vehicle (Placebo)
    Vehicle topical cream
Study Arms  ICMJE
  • Experimental: PF-06700841 0.1% cream QD
    PF-06700841 0.1% cream applied once daily (QD)
    Intervention: Drug: PF-06700841
  • Experimental: PF-06700841 0.3% cream QD
    PF-06700841 0.3% cream applied once daily (QD)
    Intervention: Drug: PF-06700841
  • Experimental: PF-06700841 1% cream QD
    PF-06700841 1% cream applied once daily (QD)
    Intervention: Drug: PF-06700841
  • Experimental: PF-06700841 3% cream QD
    PF-06700841 3% cream applied once daily (QD)
    Intervention: Drug: PF-06700841
  • Experimental: PF-06700841 0.3% cream BID
    PF-06700841 0.3% cream applied twice daily (BID)
    Intervention: Drug: PF-06700841
  • Experimental: PF-06700841 1% cream BID
    PF-06700841 1% cream applied twice daily (BID)
    Intervention: Drug: PF-06700841
  • Placebo Comparator: Vehicle cream QD
    Vehicle cream applied once daily (QD)
    Intervention: Drug: Vehicle (Placebo)
  • Placebo Comparator: Vehicle cream BID
    Vehicle cream applied twice daily (BID)
    Intervention: Drug: Vehicle (Placebo)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 20, 2021)
292
Original Estimated Enrollment  ICMJE
 (submitted: April 2, 2019)
280
Actual Study Completion Date  ICMJE May 7, 2020
Actual Primary Completion Date May 7, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years to 75 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Bulgaria,   Canada,   Denmark,   Germany,   Hungary,   Japan,   Latvia,   Poland,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03903822
Other Study ID Numbers  ICMJE B7931022
2018-003050-24 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Information relating to our policy on data sharing and the process for requesting data can be found at the following link: http://www.pfizer.com/research/clinical_trials/trial_data_and_results/data_requests
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP