A Proof of Concept Study Comparing Three Doses of an Oral Solution of LEO 22811 With a Placebo Oral Solution for the Treatment of Psoriasis Vulgaris

Study Overview
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Brief Summary
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An international, multi-centre, prospective, randomised, double-blind, 4-arm, placebo controlled, parallel group study with 12 weeks once daily oral treatment in subjects with psoriasis vulgaris.

Official Title
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An International, Multi-centre, Prospective, Randomised, Double-blind, 4-arm, Placebo Controlled, Parallel Group Study With 12 Weeks Once Daily Oral Treatment in Subjects With Psoriasis Vulgaris

Conditions
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Psoriasis Vulgaris

Intervention / Treatment
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* Drug: LEO 22811
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Following verbal and written information about the trial the subject must provide signed and dated informed consent before any study related activity is carried out, including activities relating to the washout period. Clinical diagnosis of psoriasis vulgaris, for at least 6 months prior to randomisation, and currently covering at least 10% of the body surface area (BSA) Candidates for systemic anti-psoriatic treatment Psoriasis Area and Severity Index (PASI) ≥10 Disease severity of moderate, severe or very severe according to the Investigators' Global Assessment of disease severity (IGA) Aged 18 years or above Any race or ethnicity Males, surgically sterile females (bilateral tubal ligation, bilateral oophorectomy or hysterectomy) or post menopausal females (at least 1 year since last menses) Attending hospital outpatient clinic or the private practice of a dermatologist Exclusion Criteria: Systemic treatment with biological therapies whether marketed or not with a possible effect on psoriasis vulgaris within the following time periods prior to randomisation: Etanercept - 4 weeks Adalimumab, alefacept, infliximab - 2 months Ustekinumab - 4 months Systemic treatment with all other therapies (other than biologics) with a possible effect on psoriasis vulgaris (e.g.corticosteroids, retinoids, immunosuppressants, methotrexate, cyclosporin or fumaric acid) within 4 weeks prior to randomisation PUVA therapy within 4 weeks prior to randomisation UVB therapy within 2 weeks prior to randomisation Any topical treatment (except for emollients/ medicated shampoo) within 2 weeks prior to randomisation Initiation of, or changes to concomitant medication that could affect psoriasis vulgaris (e.g. beta-blockers, anti-malaria drugs, lithium) 2 weeks prior to randomisation and during the study Current diagnosis with erythrodermic, exfoliative or pustular psoriasis Other current skin conditions that may confound the evaluation of psoriasis vulgaris as judged by the Investigator Generally in good health and does not have any clinically significant cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, haematologic, or gastrointestinal disease, immunologic insufficiency, or other major diseases or current condition which, in the opinion of the Investigator, would put the subject at risk by participating in the study Current active tuberculosis or latent tuberculosis Planned exposure to the sun during the study that may affect psoriasis vulgaris Known malignancy or history of malignancy (other than cervical carcinoma in situ, basal cell or squamous cell carcinoma) within the 5 year period prior to randomisation Live vaccination within the 4 weeks prior to randomisation Males who do not agree to use adequate contraception during the study (including follow-up) to ensure their partner does not become pregnant Known or suspected hypersensitivity to component(s) of the investigational product Current participation in any other interventional trial Treatment with any non-marketed drug substance (i.e. an agent which has not yet been made available for clinical use following registration) within 4 weeks or 5 half-lives (whichever is longer) prior to randomisation Previously randomised in this study Known or, in the opinion of the Investigator, is unlikely to comply with the Clinical Study Protocol (e.g., alcohol abuse, drug dependency or psychotic state).

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 |
| --- | --- |
| Active Comparator: LEO 22811 0.5 mg<br>LEO 22811 0.5 mg: Oral solution | Drug: LEO 22811<br>* Oral solution<br>|
| Active Comparator: LEO 22811 1.5 mg<br>LEO 22811 1.5 mg: Oral solution | Drug: LEO 22811<br>* Oral solution<br>|
| Active Comparator: LEO 22811 3.0 mg<br>LEO 22811 3.0 mg: Oral solution | Drug: LEO 22811<br>* Oral solution<br>|
| Placebo Comparator: Placebo<br>Placebo: Oral solution | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change in Psoriasis Area and Severity Index (PASI) | The investigator made assessments of the extent and severity of clinical signs of the participant's psoriasis on specific areas of the body in terms of three clinical signs: redness, thickness and scaliness. The extent of psoriatic involvement was recorded for each of four areas; head, arms, trunk and legs using the following scale: 0. = no involvement = <10% = 10-29% = 30-49% = 50-69% = 70-89% = 90-100% For each clinical sign a single score (0, 1, 2, 3 or 4) reflecting the average severity of all psoriatic lesions on the given body region was determined. PASI was calculated based on the investigator's assessment of the disease locally (head, trunk, arm, legs) using the following formula: Head: 0.1 (R + T + S)E = W Arms: 0.2 (R + T + S)E = X Trunk: 0.3 (R + T + S)E = Y Legs: 0.4 (R + T + S)E = Z R = score for redness; T = score for thickness, S = score for scaliness; E = score for extent The sum of W+X+Y+Z gives the total PASI that ranges from 0 to 72. | Baseline (Day 0) to end of treatment (Day 84) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants With at Least 75% Reduction in PASI (PASI 75) |  | From baseline (Day 0) to end of treatment (Day 84) | 
| Participants With at Least 50% Reduction in PASI (PASI 50) |  | From baseline (Day 0) to end of treatment (Day 84) | 
| Participants With Controlled Disease According to the Investigators' Global Assessment (IGA) | At Visits 1 to 8 the investigator made a global assessment of the disease severity (IGA) using a 6-point scale (clear, almost clear, mild, moderate, severe, very severe). This assessment represents average lesion severity on head, trunk, arm and legs. The assessment was based on the condition of the disease at the time of evaluation and not in relation to the condition at a previous visit. Participants classified as clear or almost clear according to IGA was considered to have controlled disease. | At end of treatment (Day 84) | 
| Participants With Satisfactory Response According to IGA | Satisfactory response was defined as participants classified as Clear or Almost Clear or Mild according to the IGA. | At end of treatment (Day 84) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psoriasis Vulgaris, Systemic, Anti-psoriatic