A Study to Assess the Efficacy and Safety of PPC-06 (Tepilamide Fumarate)

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, multicenter study designed to assess the safety and efficacy of PPC-06 (tepilamide fumarate) extended release in subjects with moderate-to-severe plaque psoriasis.

Detailed Description
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This is a Phase 2, randomized, double-blind, placebo-controlled, multicenter study designed to assess the safety and efficacy of PPC-06 in subjects with moderate-to-severe plaque psoriasis. Study subjects will be enrolled at approximately 75 sites in the United States (US). Approximately 400 subjects who meet the study entry criteria will be randomly assigned in a 1:1:1:1 ratio to 1 of the 4 treatment arms: PPC-06 400 mg once daily (QD) PPC-06 400 mg BID PPC-06 600 mg BID Placebo BID The maximum study duration for each subject will be approximately 29 weeks.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Multicenter, 24-Week Study to Assess the Efficacy and Safety of PPC-06 (Tepilamide Fumarate) Extended Release Tablets in Subjects With Moderate-to-Severe Plaque Psoriasis (AFFIRM)

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: PPC-06 400 mg QD
* Drug: PPC-06 400 mg BID
* Drug: PPC-06 600 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Generally healthy males or non-pregnant females age ≥18 years at the time of screening (or who have reached the state minimum legal age of consent). Stable, moderate-to-severe plaque psoriasis diagnosed for at least 6 months prior to randomization (no morphology changes or significant flares of disease activity in the last 6 months in the opinion of the investigator or as reported by the subject). Severity of disease meeting all 3 of the following criteria prior to randomization (at the Baseline [Day 0] visit): PASI score of ≥12 Total body surface area (BSA) affected by plaque psoriasis of ≥10% IGA score of >3 Must be a candidate for phototherapy and/or systemic therapy for psoriasis. Exclusion Criteria: Subjects with non-plaque psoriasis (ie, predominantly inverse, erythrodermic, predominantly guttate, or pustular psoriasis). Subjects with drug-induced psoriasis or subjects with drug-exacerbated psoriasis that has not resolved within 4 weeks prior to screening. Subjects who have received systemic non-biologic psoriasis therapy or phototherapy (including either oral and topical psoralen and ultraviolet A (PUVA) light therapy, ultraviolet B, or self-treatment with tanning beds or therapeutic sunbathing) within 4 weeks prior to the Baseline Visit. Subjects who had topical psoriasis treatment within the previous 2 weeks prior to the Baseline Visit. Subjects with history of concurrent or recent use of any biologic agent within the following washout periods prior to baseline visit: Etanercept - 35 days Infliximab, adalimumab - 12 weeks Ustekinumab - 24 weeks Any other biologic agent <5 half-lives prior to the Baseline Visit Subjects with history of use of any investigational drug within 28 days prior to randomization, or 5 pharmacokinetic/ pharmacodynamic half-lives (whichever is longer).

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
Interventional Model Description: Randomized
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PPC-06 400 mg QD<br>Tepilamide Fumarate 400 mg once per day | Drug: PPC-06 400 mg QD<br>* Tepilamide Fumarate 400 mg tablet once per day<br>* Other names: Tepilamide Fumarate 400 mg;|
| Experimental: PPC-06 400 mg BID<br>Tepilamide Fumarate 400 mg twice per day | Drug: PPC-06 400 mg BID<br>* Tepilamide Fumarate tablets 400 mg twice per day<br>* Other names: Tepilamide Fumarate 400 mg;|
| Experimental: PPC-06 600 mg BID<br>Tepilamide Fumarate 600 mg twice per day | Drug: PPC-06 600 mg<br>* Tepilamide Fumarate tablets 600 mg twice per day<br>* Other names: Tepilamide Fumarate 600 mg;|
| Placebo Comparator: Placebo BID<br>White placebo tablet to mimic Tepilamide Fumarate | Drug: Placebo<br>* white tablet with no active ingredient manufactured to mimic Tepilamide Fumarate tablets<br>* Other names: Placebo tablets twice per day;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Achieving Psoriasis Area and Severity Index (PASI) - 75 at the End of Week 24 | The percentage of subjects who achieve a reduction of 75% or greater from Baseline in the Psoriasis Area and Severity Index (PASI-75) The PASI is a measure of the average redness, thickness, and scaliness of the lesions (each graded on a 0-4 scale) and is weighted by the area of involvement. The minimum possible score on this scale is '0', while the maximum score on this scale is 72. A lower score on this scale at the end of the study indicates an improvement in the condition of subject. | End of Week 24 | 
| Achieving the Investigator's Global Assessment (IGA) Score of 0 or 1 | The Percentage of subjects who achieve the Investigator's Global Assessment (IGA) score of clear or almost clear (IGA score 0 or 1) Score Grade Definition 0 Clear: No signs of psoriasis Almost clear: No thickening to minimal plaque elevation; Normal to slight pink coloration/faint erythema; Focal to minimal scaling Mild: Slight elevation/thickening; Pink to light red coloration; Predominantly fine scaling partially or mostly covering lesions Moderate: Clearly distinguishable/distinct thickening; Definite red coloration; Coarse scaling covering most plaques Severe: Marked thickening with hard/sharp edges; Bright to deep dark red coloration; Thick/coarse scaling covering almost all or all lesions A lower score on this scale at the end of the study indicates an improvement in the disease condition. | End of Week 24 |