A Study to Assess the Efficacy and Safety of XP23829 in Subjects With Moderate-to-Severe Chronic Plaque-Type Psoriasis

Study Overview
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Brief Summary
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The study objectives are the following: To evaluate the efficacy of 3 doses of XP23829 compared to placebo for the treatment of moderate-to-severe chronic plaque-type psoriasis. To evaluate the safety and tolerability of XP23829 in subjects with psoriasis. To evaluate the pharmacodynamics (PD) of XP23829 through immunological analysis of peripheral blood samples.

Detailed Description
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Study Design : This is a , multi-center, double blind, placebo-controlled, phase 2 (dose-finding) efficacy and safety study in which subjects with moderate-to- severe chronic plaque-type psoriasis will be randomized in a 1:1:1:1 allocation ratio to 1 of 3 active doses of XP23829 or placebo. Approximately 50 subjects will be enrolled into each treatment group. Study Periods: The study includes a 4-week screening phase, a 12-week treatment phase (with 9 weeks of XP23829 or placebo at the maintenance dose), and a 4-week observational post-treatment follow-up phase. A treatment-free follow-up period is designed to evaluate safety and disease relapse and rebound. Specifically, the study periods are as follows: Screening Phase: Weeks -4 through 0 Treatment phase included: Titration Phase: Weeks 1 through 3 Double-Blind Maintenance Phase: Weeks 4 through 12 Post-treatment follow-up: Weeks 13 through 16 Efficacy assessments will be performed in the clinic at Baseline (Visit 2) and at the end of Weeks 2, 4, 8, 12, 14, and 16. Patient-reported outcome measures will be assessed in the clinic at Baseline and at Week 12. Blood samples for pharmacodynamic (PD) assessments will be collected at Baseline and at Weeks 4, 8, 12 and 16. PD assessments will be conducted in all subjects, with the intent of evaluating psoriasis-associated inflammatory markers.

Official Title
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A Phase 2, Randomized, Double-Blind, Multicenter, Parallel-Group, Placebo-Controlled Study to Assess the Efficacy and Safety of Three Dose Levels of XP23829 in Subjects With Moderate-to-Severe Chronic Plaque-Type Psoriasis

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: XP23829 400 mg QD
* Drug: XP 23829 800 mg QD
* Drug: XP23829 400 mg BID
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects, age ≥ 18. Stable, moderate-to-severe plaque-type 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). Severity of disease meeting all of the following three criteria prior to randomization: Psoriasis Area and Severity Index (PASI) score of 12 or greater Total Body Surface Area (BSA) affected by plaque psoriasis of 10% or greater Static Physician's Global Assessment (sPGA) score of 3 or greater Must be a candidate for phototherapy and/or systemic therapy for psoriasis. Exclusion Criteria: Subjects with current inverse, erythrodermic, predominantly guttate, or pustular psoriasis. Subjects with current drug-induced or drug-exacerbated psoriasis. Subjects with moderate-to-severe psoriatic arthritis of any type; and subjects with mild psoriatic arthritis, who require systemic disease-modifying therapy. Subjects with unstable or significant illness, including the presence of laboratory abnormalities at screening that in the opinion of the investigator would place the subject at unacceptable risk if he/she were to participate in the study. Any skin condition (e.g. eczema) which confounds the ability to interpret data from the study. Treatment with a topical anti-psoriatic therapy within 14 days prior to randomization (including topical steroids, topical vitamin A or D analog preparations, tacrolimus, pimecrolimus, or anthralin). Phototherapy or prolonged sun exposure or use of ultraviolet (UV) light sources within 28 days of randomization. Use of investigational or approved biologic treatments that are known to affect psoriasis, such as adalimumab, etanercept, golimumab or infliximab within 12 weeks of randomization and ustekinumab within 24 weeks of randomization. Use of systemic medications (non-biologics) that are known to affect psoriasis (including but not limited to oral corticosteroids, cyclosporine, methotrexate, lithium, and beta-adrenergic blockers) within 4 weeks of randomization, or 5 half-lives, whichever is longer. Prior treatment with Dimethyl Fumarate (Fumaderm® or Tecfidera®) or any other Fumaric Acid Ester (FAE) containing products. Have failed (due to inadequate response) more than 3 approved systemic agents for the treatment of psoriasis.

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: XP23829 400 mg QD (once daily)<br>After 4-week screening period, eligible subjects will be randomized to XP23829 400 mg QD for 12 weeks including titration period | Drug: XP23829 400 mg QD<br>* active dose 1<br>* Other names: PPC-06 400 mg QD;|
| Experimental: XP23829 800 mg QD<br>After 4-week screening period, eligible subjects will be randomized to XP23829 800 mg QD for 12 weeks including titration period | Drug: XP 23829 800 mg QD<br>* active dose 2<br>* Other names: PPC-06 800 mg QD;|
| Experimental: XP23829 400 mg BID (twice daily)<br>After 4-week screening period, eligible subjects will be randomized to XP23829 400 mg BID for 12 weeks including titration period | Drug: XP23829 400 mg BID<br>* active dose 3<br>* Other names: PPC-06 400 mg BID;|
| Placebo Comparator: Placebo<br>After 4-week screening period, eligible subjects will be randomized to Placebo for 12 weeks | Drug: Placebo<br>* control<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| • The Percent Change in PASI (Psoriasis Area and Severity Index) Score From Baseline | 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. | 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| • Proportion of Subjects Who Achieve a Reduction of 75% or Greater From Baseline in PASI (PASI-75) | The percentage of subjects who achieve a reduction of 75% or greater from Baseline in the Psoriasis Area and Severity Index score (PASI-75) at efficacy assessments conducted at Weeks 2, 4, 8, 12, 14 and 16. 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. | Weeks 2, 4, 8, 12, 14 and 16 | 
| • Proportion of Subjects Who Achieve a sPGA (Static Physician's Global Assessment) Score of Clear or Almost Clear | The Percentage of subjects who achieve the static Physician's Global Assessment (sPGA) score of 'clear' or 'almost clear' (sPGA score 0 or 1) at efficacy assessments conducted at Weeks 2, 4, 8, 12, 14 and 16. 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. | Weeks 2, 4, 8, 12, 14 and 16 |