A Study to Determine the Efficacy of ZPL-3893787 in Subjects With Plaque Psoriasis

The PASI is an assessment routinely used for evaluating and grading the severity of psoriatic lesions and their response to therapy. PASI divides the body into 4 regions: the head, trunk, upper extremities (arms) and lower extremities (legs). Each of these areas is assessed separately for erythema, in duration and scaling; these symptoms are scored on a 5-point scale from 0-4, where 0 = no symptoms and 4 =very marked. The PASI produces a numeric score that can range from 0 to 72. A higher score indicates more severe disease. A PASI 75 response represents a reduction of at least 75% from baseline in the PASI score.

PASI-75 and PASI-50 are defined as a 75% and 50% reduction, respectively, from baseline in PASI score at Week 12.

An overall assessment of the severity of psoriasis was made, by the investigator, using the IGA at each visit. IGA scores take values on a 5-point scale from 0-4, where 0 = clear to 4 = severe disease. Responder is defined as a score of clear or almost clear, or a reduction of ≥2 levels. Success is defined as a score of clear or almost clear. Subjects with discontinued and missing data categories at Week 12 were considered non-responders.

The pruritus NRS is an assessment tool used to assess the subject's worst itch as a result of psoriasis in the last 12 hours. The subjects completed the NRS each morning on (or soon after) rising and evening prior to retiring to bed. The subjects completed the NRS each morning on (or soon after) rising and evening prior to retiring to bed. They were asked the following question: On a scale of 0 (no itching) to 10 (itching as bad as you can imagine), please rate the worst itching that you felt over the last 12 hours.

At the end of treatment (Week 12) or early termination visit, the subject was asked to rate their degree of improvement (or worsening) of their psoriasis compared to before the start of treatment with study drug, using a 7-point scale, standardized PGIC.

Since the start of the study (dosing), my overall status is:

• Very much improved
• Much improved
• Minimally improved
• No change
• Minimally worse
• Much worse
• Very much worse

Assessment of the percentage of a subject's BSA affected by psoriasis was made by best estimates of the investigator at each visit. Hand-size measurement was considered to be the "best estimate" to measure the BSA by the investigators.

The subjects completed the NRS each morning on (or soon after) rising and evening prior to retiring to bed. They were asked the following question: On a scale of 0 (no itching) to 10 (itching as bad as you can imagine), please rate the worst itching that you felt over the last 12 hours.

In the morning subjects were asked the following question to determine the level of sleep disturbance due to itching: On a scale of 0 (no sleep disturbance) to 10 (awake all night), please rate how much your sleep was disturbed by itch last night.

Subjects were asked the following question to determine their duration of itching: Over the last 12 hours approximately how many hours, if any, did you itch?

Subjects were asked to rate their itch over the last 12 hours using a list of adjectives describing different levels of symptom intensity: Over the last 12 hours how would you rate your itch? No itch; Mild; Moderate and Severe; Pruritus was evaluated by the subject, using the eDiary, twice daily for 1 week prior to the start of study treatment (run-in period) and during treatment (baseline to Day 84).