Study to Assess the Efficacy and Safety of Orismilast in Psoriasis

Study Overview
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Brief Summary
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This study investigates 3 different doses of orismilast modified release compared to placebo in adult patients with moderate-to-severe plaque-type psoriasis. The purpose of the study is to assess the effect of orismilast modified release in moderate-to-severe plaque-type psoriasis and assess the safety aspects of these 3 different doses.The patients will receive an oral treatment of either orismilast modified release tablets or placebo tablets 2 times a day for 16 weeks.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 2b Dose-Ranging Study to Evaluate the Efficacy and Safety of Orismilast in Adults With Moderate-to-Severe Plaque-Type Psoriasis

Conditions
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Psoriasis, Skin Diseases

Intervention / Treatment
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* Drug: Orismilast modified release tablets
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Capable of giving signed informed consent. Male and female patients ≥18 years of age Body weight of >40 kg Diagnosis of chronic, stable plaque-type psoriasis. If the patient is diagnosed with psoriasis arthritis, the arthritis should be stable. Moderate-to-severe plaque-type psoriasis as defined by PASI ≥12, BSA ≥10%, and IGA ≥3. Candidate for systemic antipsoriatic treatment or phototherapy. Exclusion Criteria: Therapy-resistant psoriasis Unstable psoriasis or psoriatic arthritis with acute deterioration within 4 weeks of the Screening visit. History of allergy or hypersensitivity to any component of the study treatment. Active infection (eg, bacteria, viral, fungal) requiring treatment with systemic antibiotics within 4 weeks of the Screening visit. Malignancy or history of malignancy except for treated (ie, cured) basal cell skin carcinomas.

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: Participants will be assigned randomly in a 1:1:1:1 ratio to receive 1 of the 3 orismilast modified release doses (20 mg, 30 mg, or 40 mg) or placebo twice daily (BID)
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Orismilast modified release tablets 20 mg BID<br>Oral, twice daily morning and evening | Drug: Orismilast modified release tablets<br>* Orismilast modified release is a next generation PDE4 inhibitor with high selectivity for the PD4 subtypes linked to inflammation.<br>* Other names: LEO32731;|
| Experimental: Orismilast modified release tablets 30 mg BID<br>Oral, twice daily morning and evening | Drug: Orismilast modified release tablets<br>* Orismilast modified release is a next generation PDE4 inhibitor with high selectivity for the PD4 subtypes linked to inflammation.<br>* Other names: LEO32731;|
| Experimental: Orismilast modified release tablets 40 mg BID<br>Oral, twice daily morning and evening | Drug: Orismilast modified release tablets<br>* Orismilast modified release is a next generation PDE4 inhibitor with high selectivity for the PD4 subtypes linked to inflammation.<br>* Other names: LEO32731;|
| Placebo Comparator: Placebo tablets BID<br>Oral, twice daily morning and evening | Drug: Placebo<br>* Matching placebo tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from Baseline in Psoriasis Activity and Severity Index (PASI) score at Week 16 | The PASI is a measure of psoriatic disease severity, taking into account qualitative lesion characteristics (erythema, induration, and desquamation) and percentage of affected skin surface area on defined anatomical regions. | Day 1 to Week 16. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients achieving 75% reduction in PASI (PASI75) response at Week 16. | The PASI is a measure of psoriatic disease severity, taking into account qualitative lesion characteristics (erythema, induration, and desquamation) and percentage of affected skin surface area on defined anatomical regions. | Day 1 to Week 16 | 
| Patients achieving a score of Clear (0) or Almost Clear (1) and an at least 2-point improvement in Investigator Global Assessment (IGA) at Week 16. | The IGA is a measure used by physicians to determine the patient's overall severity of disease. The static version (Langley 2015) is used in this trial for measurement at a single point in time as indicated in the schedule of assessments. The investigator will rate the severity of patient's psoriasis on a 5-point scale ranging from 0 (clear) to 4 (severe). | Day 1 to Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psoriasis, Orismilast