Safety, Tolerability And Efficacy Study Of Topical PF-06763809 In Subjects With Mild To Moderate Chronic Plaque Psoriasis

Study Overview
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Brief Summary
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The study is a randomized, double blinded, vehicle and active comparator controlled, multiple dose study in subjects with chronic plaque psoriasis. The study will have approximately 15 completers. Each subjects will receive three different topical doses of PF 06763809, PF 06763809 vehicle, and two active comparators. These will be applied to six different treatment fields for 18 days. The total duration of participation in the study will be approximately 7 weeks (minimum) to approximately 11 weeks (maximum), including the interval from Screening to the Follow up phone call visit.

Official Title
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A PHASE 1, RANDOMIZED, DOUBLE-BLIND, VEHICLE AND ACTIVE COMPARATOR-CONTROLLED, PSORIASIS PLAQUE TEST STUDY TO ASSESS SAFETY, TOLERABILITY, AND PSORIATIC SKIN INFILTRATE THICKNESS FOLLOWING REPEATED, TOPICAL DOSES OF PF-06763809 SOLUTION IN SUBJECTS WITH MILD TO MODERATE CHRONIC PLAQUE PSORIASIS

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: PF-06763809
* Other: Vehicle
* Drug: Calcipotriene/calcipotriol
* Drug: Betamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Psoriasis vulgaris in a chronic stable phase and with a plaque area of mild to moderate severity sufficient for six treatment fields located in up to three plaque areas Target lesion(s) should be on the trunk or extremities (excluding palms/soles). Exclusion Criteria: History of skin sensitivity to topical prescription or non prescription products such as creams, lotions and cosmetics Psoriasis guttata, psoriasis punctata, psoriasis erythrodermatica, and pustular psoriasis Treatment with any biologics within 3 months prior to Day 1 of the study and during the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: All subjects<br>All subjects will receive all six interventions/treatments applied to six different treatment fields. | Drug: PF-06763809<br>* Three different concentrations will be administered to three different treatment fields: 2.3%, 0.8% and 0.23%<br>Other: Vehicle<br>* Vehicle matching PF-06763809.<br>Drug: Calcipotriene/calcipotriol<br>* Calcipotriene/calcipotriol 50 ug/mL solution<br>Drug: Betamethasone<br>* Betamethasone 1 mg/g solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Psoriatic Skin Infiltrate Thickness | Baseline was defined to be the measurement on Day 1. MMRM analysis of changes in psoriatic skin in psoriatic skin infiltrate thickness/echo poor band (EPB) in response to PF-06763809 2.3%, 0.8% and 0.23% applied topically for 18 consecutive days as compared to the vehicle control. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Baseline, Days 7, 13 and 19 | 
| Number of Participants With Treatment-emergent Adverse Events (AEs) | Baseline was defined to be the measurement on Day 1. An AE was any untoward medical occurrence in a clinical investigation patient administered a product or medical device. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of investigational product. | Day 1 to Day 49 | 
| Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Baseline was defined to be the measurement on Day 1. The safety laboratory tests including Hematology, Clinical Chemistry and Urinalysis were performed. Hematology evaluation included: hemoglobin (HGB) (gram per decilitre=g/dL), hematocrit, erythrocytes (Ery.), Ery. Mean Corpuscular Volume, Ery. Mean Corpuscular Hemoglobin, Ery. Mean Corpuscular HGB Concentration (picograms per cell=pg/cell), platelets, leukocytes, lymphocytes, and neutrophils. Clinical chemistry evaluation included: bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, protein, albumin, urea nitrogen, urea, creatinine, urate, sodium, potassium, chloride, calcium, bicarbonate, creatine kinase, and glucose. Urinalysis evaluation included: pH, urine glucose, ketones, urine protein, urine hemoglobin, urobilinogen, urine bilirubin, nitrite, and leukocyte esterase. LLN=lower limit of normal, ULN=upper limit of normal. | Day 1 to Day 49 | 
| Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria | Baseline was defined to be the measurement on Day 1. ECG categorical summarization criteria: 1) PR interval (Value>=300 milliseconds [msec], %Change [Chg]>=25/50%); 2) QRS interval (Value>=140 msec, >=50% change from baseline; 2) PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): >=300 msec, >=25% change when baseline is > 200 msec or >=50% change when baseline is less than or equal to (<=) 200 msec; 3) QT interval (time from ECG Q wave to the end of the T wave corresponding to electrical systole): absolute value of >=500 msec; 4) QTc interval (QT corrected for heart rate): absolute value of 450 to <480 msec, 480 to <500 msec, >=500 msec; a change from baseline of 30 to <60 msec or >=60 msec. The corrected QT interval by Fredericia=QTcF Interval. | Day 1 to Day 49 | 
| Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria | Baseline was defined to be the measurement on Day 1. Vital Signs including diastolic blood pressure (DBP), pulse rate, and systolic blood pressure (SBP) were measured. | Day 1 to Day 49 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve of the Psoriatic Skin Infiltrate Thickness | Baseline was defined to be the measurement on Day 1. To evaluate the Area Under the Curve (AUC) of psoriatic skin infiltrate thickness/EPB for PF 06763809 compared to vehicle by mixed model analysis. The AUC of the psoriatic skin infiltrate thickness/EPB from Day 1 to Day 19 was determined using the linear trapezoidal rule. The log AUC was performed by the natural logarithm of the AUC of the psoriatic skin infiltrate thickness/EPB. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Day 1 to Day 19 | 
| Change From Baseline in Skin Infiltrate Thickness in Response to PF-06763809 Compared to Calcipotriene/Calcipotriol Solution. | The effect of PF-06763809 compared to calcipotriene/calcipotriol solution in the change of psoriatic skin infiltrate thickness/EPB both within and following 18 days of treatment. Baseline was defined to be the measurement on Day 1. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Baseline, Days 7, 13 and 19 | 
| Change From Baseline in Skin Infiltrate Thickness in Response to PF-06763809 Compared to Betamethasone Solution. | The effect of PF-06763809 compared to betamethasone solution in the change of psoriatic skin infiltrate thickness/EPB both within and following 18 days of treatment. Baseline was defined to be the measurement on Day 1. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Baseline, Days 7, 13 and 19 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psoriasis, Topical