A 12 Day Study To Evaluate A Topical Drug To Treat Plaque Psoriasis

Study Overview
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Brief Summary
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This is a vehicle and comparator controlled Proof of Mechanism (PoM) trial to evaluate the effect on psoriasis disease activity and safety of topically applied PF 06263276 in subjects with psoriasis vulgaris.

Official Title
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A Phase 1, Single- Center, Randomized, Double-blind, Vehicle And Active Comparator-controlled Trial To Evaluate The Antipsoriatic Activity And Safety Of A Topically Applied Pf-06263276 Formulation In A Psoriasis Plaque Test

Conditions
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Psoriasis Vulgaris

Intervention / Treatment
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* Drug: PF06263276
* Other: Vehicle
* Drug: 2%Tofacitinib Ointment
* Other: Vehicle
* Drug: Daivonex
* Drug: Daivonex Ointment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and/or female subjects age 18 years and older, inclusive. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12 lead ECG or clinical laboratory tests. Subjects with 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. The target lesion(s) should be on the trunk or extremities (excluding palms/soles). Psoriatic lesions on the knees or elbows are not to be used as a target lesion. Exclusion Criteria: Subjects with psoriasis guttata, psoriasis punctata, psoriasis erythrodermatica, psoriasis arthropathica and pustular psoriasis. Treatment with any systemic medications which in the opinion of the investigator might counter or influence the trial aim (including anti psoriasis medications, eg, corticosteroids, cytostatics or retinoids) or medications which are known to provoke or aggravate psoriasis (eg, beta blocker, anti malarial drugs, lithium) or phototherapy/psoralen+UVA (PUVA) within 4 weeks preceding the treatment phase of the trial and during the trial. Treatment with any locally acting medications (including anti-psoriasis medications like vitamin D analogues, dithranol) within 4 weeks of the treatment phase.

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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: One Arm<br>Study treatments 1-6 Study drug, vehicle, Tofacitinib, vehicle, Daivonex solution and ointment | Drug: PF06263276<br>* 4% PF 06263276 solution Daily dosage: approximately 8 mg PF 06263276 QD<br>Other: Vehicle<br>* Active ingredient-free vehicle to 4% solution<br>Drug: 2%Tofacitinib Ointment<br>* Daily Dosage: approximately 4 mg tofacitinib<br>Other: Vehicle<br>* Active ingredient-free vehicle to 2% Ointment<br>Drug: Daivonex<br>* Daivonex solution (50 ug/ml Calcipotriol) Daily Dosage of calcipotriol: approximately 0.01 mg<br>Drug: Daivonex Ointment<br>* Daivonex ointment (50 ug/g Calcipotriol) Daily Dosage of calcipotriol: approximately 0.01 mg<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 Thickness/Echo-Poor Band (EPB) for PF-06263276 4% Solution in Comparison to Corresponding Vehicle at Day 12 | Psoriatic skin thickness was measured using a 20 megahertz (MHz) high frequency sonograph. Serial A-scans were composed and presented on a monitor as a section of the skin. | Day 1 (Baseline), Day 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Psoriatic Skin Thickness/EPB for PF-06263276 4% Solution in Comparison to Daivonex Solution at Day 12 |  | Day 1 (Baseline), Day 12 | 
| Change From Baseline in Psoriatic Skin Thickness/EPB for Tofacitinib 2% Ointment in Comparison to Corresponding Vehicle at Day 12 |  | Day 1 (Baseline), Day 12 | 
| Change From Baseline in Psoriatic Skin Thickness/EPB at Day 8 |  | Day 1 (Baseline), Day 8 | 
| Area Under the Curve (AUC) of Psoriatic Skin Thickness/EPB | The AUC of psoriatic skin thickness/EPB from Day 1 to Day 12 was determined using the linear trapezoidal rule. The mean raw values are reported. | Day 1 (baseline) up to Day 12 | 
| Global Clinical Assessment at Day 1, 8 and 12 | Global Clinical Assessment of the test fields was performed by visual examination using a 5-point score (-1=worsened; 0=unchanged [no effect]; 1=slight improvement; 2=clear improvement but not completely healed; 3=completely healed). Clinically apparent differences in erythema and infiltration will contribute to this global assessment. At baseline (Day 1), the score was documented as 0 (unchanged). | Day 1, Day 8, Day 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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psoriasis, plaque, vulgaris, phase 1, randomized, double-blind, topical, safety