An Efficacy and Safety Study of LYC-30937-EC in Subjects With Moderate Chronic Plaque-type Psoriasis

Study Overview
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Brief Summary
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The objective of this Phase 2 trial is to determine the efficacy and safety of LYC-30937-EC in patients with moderate plaque-type psoriasis.

Detailed Description
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Approximately 30 subjects will be enrolled in this double-blind, placebo-controlled study. The randomization will be stratified 2:1 into the LYC-30937-EC cohort (2) or the placebo cohort (1). The active cohort will receive LYC-30937-EC 25 mg once daily, which demonstrated safety and tolerability in Phase I trials. The study is designed for patients with previously diagnosed moderate chronic plaque-type psoriasis and consists of the following: Screening period (initials assessment and eligibility scoring) Day 1: confirm eligibility, baseline efficacy assessments (PASI, IGA), randomize and initiate dosing Week 2: safety assessments including vital signs, body temperature, physical exam, clinical labs will be performed Week 4: efficacy (PASI, IGA) and safety assessments including vital signs, body temperature, physical exam, and clinical labs will be performed Week 8: efficacy (PASI, IGA) and safety assessments including vital signs, body temperature, physical exam, and clinical labs will be performed Week 12: final efficacy assessments (PASI, IGA), safety assessments including vital signs, body temperature, physical exam, ECG, and clinical labs will be performed Week 14: final safety assessments including vital signs, body temperature, and clinical labs

Official Title
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A Randomized, Placebo-Controlled, Double-Blind Study to Assess the Efficacy and Safety of LYC-30937-EC in Subjects With Moderate Chronic Plaque-Type Psoriasis

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: Drug: LYC-30937-EC
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of plaque-type psoriasis for at least 6 months prior to screening. Must have chronic moderate plaque-type psoriasis confirmed at both screening and baseline visits. Moderate plaque-type psoriasis is defined as a PASI > 7, with body surface area (BSA) involvement 5-15% inclusive and overall lesion severity of moderate or marked,  where moderate = plaque elevation (0.75mm), moderate red coloration, coarse scale predominates; marked = moderate plaque elevation (1.0mm), bright red coloration, and thick, non-tenacious scale predominates. Female subjects of childbearing potential must agree to use two highly effective forms of contraception during study participation and for 30 days after their last dose of treatment of study drug treatment. Male subjects with partners of childbearing potential must take appropriate precautions to avoid fathering a child while participating in the study and use appropriate barrier contraception or abstinence during the study and for 30 days after their last dose of study drug. Agree to avoid prolonged sun exposure and avoid tanning booths or ultraviolet (UV) light sources during the study. Ability to provide written informed consent and to be compliant with the schedule of events. Exclusion Criteria: Non-plaque-type psoriasis (eg, pustular, erythrodermic, and guttate psoriasis). Drug-induced psoriasis (ie, new onset or current exacerbation from beta-blockers, calcium channel blockers, or lithium). Spontaneously improving or rapidly deteriorating plaque psoriasis. Comorbid psoriatic arthritis that is not amenable to treatment with NSAIDs. Treatment with a biologic agent for psoriasis. Failed 2 or more systemic treatments for plaque psoriasis. Received phototherapy or prolonged sun exposure or use of tanning booth or other ultraviolet light source within 4 weeks of initiating screening procedures. Received systemic drug therapy (non-biologic) for plaque psoriasis or any systemic medication that could affect psoriasis or its evaluation (PASI or IGA), including but not limited to oral or injectable corticosteroids, retinoids, sulfasalazine, within 4 weeks of initiating screening procedures. Received topical medication that could affect psoriasis or its evaluation (PASI or IGA), including but not limited to corticosteroids, retinoids, topical vitamin D derivatives, pimecrolimus, tacrolimus, calcipotriene, within 2 weeks of initiating screening procedures. Received immunosuppressant agents (eg, cyclosporine, azathioprine, methotrexate) within 8 weeks of initiating screening procedures. Any of the following laboratory abnormalities: liver function tests > 1.5 x the upper limit of normal (ULN) or direct bilirubin > 1.5 x ULN hemoglobin < 8.5 g/dl (international system units [SI]: < 85 g/L) neutrophils < 1500/mm3 (SI: < 1.5 x 109/L) white blood cell (WBC) count < 3,000/mm3 (SI: < 3.0 x 109/L) platelets < 80,000 mm3 (SI: 80 x 109/L) international normalized ratio (INR) > 1.5 serum creatinine > 1.4 mg/dL for women or > 1.6 mg/dL for men Clinically relevant hepatic, neurological, pulmonary, dermatological, ophthalmological, gastrointestinal, endocrine, psychiatric, or other major systemic disease making implementation of the protocol or interpretation of the study difficult or that would put the subject at risk by participating in the study. History of or currently active primary or secondary immunodeficiency. Treatment with an investigational agent within 30 days prior to initiating screening procedures.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: LYC-30937-EC 25 mg PO once daily (QD)<br>LYC-30937-EC 25 mg by mouth once daily for 12 weeks | Drug: Drug: LYC-30937-EC<br> <br> |
| Placebo Comparator: Matching Placebo PO QD<br>Placebo enteric coated (EC) by mouth once daily for 12 weeks | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Mean Percent Change From Baseline to Week 12 in Psoriasis Area and Severity Index (PASI). | This endpoint was calculated in each treatment group by taking the Week 12 PASI score and subtracting the baseline PASI and dividing by the baseline PASI, then multiplying by 100 to get the percent change from baseline. The PASI is a measure of chronic plaque-type psoriasis disease. It combines lesion severity (erythema, thickness, scaling) and skin surface area involvement in 4 defined anatomical body regions (head, upper extremities, trunk, lower extremities). PASI score ranges from 0 to 72 with higher scores indicative of greater disease severity. Lesion severity (erythema, thickness, scaling) is scored on a scale of 0 (none) to 4 (very severe) on each of the 4 body regions. Degree of skin area involvement in each body region is scored on a scale of 0 (no involvement) to 6 (90-100% involvement). | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Subjects Who Achieve a ≥ 75% Reduction From Baseline in PASI at Week 12. | This endpoint calculated the number of subjects achieving a ≥ 75% reduction in their Week 12 PASI score compared to their baseline PASI. The PASI is a measure of chronic plaque-type psoriasis disease. It combines lesion severity (erythema, thickness, scaling) and skin surface area involvement in 4 defined anatomical body regions (head, upper extremities, trunk, lower extremities). PASI score ranges from 0 to 72 with higher scores indicative of greater disease severity. Lesion severity (erythema, thickness, scaling) is scored on a scale of 0 (none) to 4 (very severe) on each of the 4 body regions. Degree of skin area involvement in each body region is scored on a scale of 0 (no involvement) to 6 (90-100% involvement). | Baseline to Week 12 | 
| The Mean Percent Change From Baseline to Week 12 in Percent Body Surface Area (BSA). | Mean percent change from baseline to Week 12 in %BSA was calculated by taking the Week 12 %BSA and subtracting the baseline %BSA then dividing by the baseline %BSA and multiplying by 100. The mean percent change from baseline to Week 12 in each treatment group were compared using analysis of covariance with treatment as a factor and baseline as a covariate. | Baseline to Week 12 | 
| The Number of Subjects Who Achieve Cleared (Score = 0) or Minimal (Score = 1) on the Static Investigators Global Assessment at Week 12. | This endpoint is number of subjects who achieved a score of 0 or 1 on the static IGA at week 12. The static IGA is used to measure psoriasis severity. The static IGA used in this study was a 6-point scale: 0 = Cleared [no plaque elevation, erythema or scaling, hyperpigmentation may be present]; 1 = Minimal [minimal plaque elevation (=0.25mm), faint erythema, minimal scaling with occasional fine scale over < 5% of lesion]; 2 = Mild [mild plaque elevation (=0.5mm), light red coloration, fine scale predominates]; 3 = Moderate [moderate plaque elevation (=0.75mm), moderate red coloration, coarse scale predominates]; 4 = Marked (marked plaque elevation (=1mm), bright red coloration, thick non-tenacious scale predominates]; 5 = Severe (severe plaque elevation (≥1.25mm), dusky to deep red coloration, very thick tenacious scale predominates]. | 12 weeks | 
| The Number of Subjects Who Achieve a 2 Step Reduction on the Static Investigators Global Assessment (IGA) at Week 12. | This endpoint is based on number of subjects who achieved a 2 step reduction in the static IGA at week 12 (ie, a score of 5 at baseline to a score of 3 or less at Week 12). The static IGA is used to measure psoriasis severity. The static IGA used in this study was a 6-point scale: 0 = Cleared [no plaque elevation, erythema or scaling, hyperpigmentation may be present]; 1 = Minimal [minimal plaque elevation (=0.25mm), faint erythema, minimal scaling with occasional fine scale over < 5% of lesion]; 2 = Mild [mild plaque elevation (=0.5mm), light red coloration, fine scale predominates]; 3 = Moderate [moderate plaque elevation (=0.75mm), moderate red coloration, coarse scale predominates]; 4 = Marked (marked plaque elevation (=1mm), bright red coloration, thick non-tenacious scale predominates]; 5 = Severe (severe plaque elevation (≥1.25mm), dusky to deep red coloration, very thick tenacious scale predominates]. | 12 weeks |