Study to Determine if AZD0284 is Effective and Safe in Treating Plaque Psoriasis

Study Overview
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Brief Summary
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The Sponsor is developing the study drug, AZD0284, for the potential treatment of Plaque psoriasis. Psoriasis is a skin condition that causes red, flaky, crusty patches of skin covered with silvery scales. The severity of the disease varies, but in many cases it can have a major impact on their quality of life if not adequately treated. The purpose of the study is to determine the short term safety, pharmacodynamic and clinical effect of AZD0284 in patients with psoriasis.

Detailed Description
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This is a randomised, double-blind, placebo-controlled, multi-centre, parallel group Phase 1b study, designed to evaluate the pharmacodynamic effects, clinical efficacy and safety of AZD0284 compared with placebo as measured by the relative change from baseline in Psoriasis Area Severity Index (PASI score), other disease assessments of involved body surface area (BSA), static physicians global assessment score (sPGA), pruritis and biomarkers associated with the mechanism of disease and AZD0284. Disease activity will be assessed throughout the study as will changes in skin biopsy biomarkers. The study population will be comprised of patients with moderate to severe plaque psoriasis as defined by PASI score, BSA and sPGA. Following completion of screening assessments and meeting all eligibility criteria, patients will be randomised to receive AZD0284 or placebo for 4 weeks of treatment followed by a 4 week follow up period

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Phase 1b Study to Assess Efficacy and Safety of One Dose Level of Oral AZD0284 Given for Four Weeks, Compared to Placebo, in Patients With Moderate to Severe Plaque Psoriasis

Conditions
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Plaque Psoriasis Vulgaris

Intervention / Treatment
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* Drug: AZD0284 oral solution 2.5 mg/mL
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed informed consent prior to any study specific procedures. At least 6 months documented history with a diagnosis of moderate to severe plaque psoriasis as defined by the Psoriasis Area and Severity Index (PASI), psoriasis Body Surface Area (BSA) and static Physician Global Assessment (sPGA). Exclusion Criteria: History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or influence the results or the patient's ability to participate in the study. History and/or presence of tuberculosis, hepatitis, HIV. Other opportunistic infections within 6 months of the study. Clinically significant laboratory abnormalities. Clinically important abnormalities in rhythm, conduction or morphology of the digital Electrocardiogram (ECG) as considered by the Investigator may interfere with the interpretation of study data. Current treatment or treatment for psoriasis with biological therapies within 6 months of study. Efficacy and safety failure of biologic therapies targeting the IL-17 and IL12/23 pathway at any time. Current treatment or history of treatment for psoriasis with non-biological systemic medications within 4 weeks of Day 1

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
Interventional Model Description: This is a randomised, double-blind, placebo-controlled, multi-centre, parallel group Phase 1b study in patients with moderate to severe plaque psoriasis. The study is designed to evaluate the pharmacodynamic effects, clinical efficacy and safety of AZD0284 compared with placebo as measured by the relative change from baseline in Psoriasis Area and Severity Index score and biomarkers associated with the mechanism of disease and AZD0284. It comprises 8 clinic visits over approximately 10 weeks including screening visit.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo for AZD0284 oral solution | Drug: Placebo<br>* Placebo for AZD0284 oral solution, twice daily for 4 weeks<br>|
| Experimental: AZD0284<br>AZD0284 oral solution 2.5 mg/mL | Drug: AZD0284 oral solution 2.5 mg/mL<br>* AZD0284 oral solution 2.5 mg/mL, 100 mg twice daily for for 4 weeks<br>* Other names: AZD0284;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction from baseline to the end of treatment, in gene expression level of IL-17A and CCL20 relative to placebo. | Reduction from baseline to the end of treatment, in gene expression level of IL-17A and CCL20 relative to placebo. | 4 weeks | 
| Percent improvement from baseline to the end of treatment in individual Psoriasis Area and Severity Index (PASI) compared to placebo | Change (percent improvement) in Psoriasis Area and Severity Index score(PASI) compared to placebo | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients achieving 75 % reduction from baseline in PASI score, i.e. PASI 75, at week 4 | Percent patients acheiving a 75% reduction in PASI score | 4 weeks | 
| Proportion of patients achieving 50 % reduction from baseline in PASI score, i.e. PASI 50, at week 4 | Percent patients acheiving a 50% reduction in PASI score | 4 weeks | 
| Reduction in static physician's global assessment (sPGA) score from baseline at week4 | The change in the Static physician's global assessment (sPGA) score will be assessed | 4 weeks | 
| Percent improvement from baseline in involved body surface area (BSA) at week 4 | The percent change in the involved body surface area (BSA) will be assessed | 4 weeks | 
| Reduction in the pruritus visual analogue scale (pVAS) score from baseline, at week 4 | The reduction in the pruritus visual analogue scale (pVAS) score as determined by the patient will be assessed | 4 weeks | 
| Cmax : maximum observed plasma concentration | Maximum observed plasma concentration (Cmax) will be assessed | 4 weeks | 
| tmax time to reach Cmax | The time to reach the maximum observed plasma concentration (Cmax) will be assessed | 4 weeks | 
| Cmin minimum observed plasma concentration | The minimum observed plasma concentration (Cmin) will be assessed | 4 weeks | 
| AE(s) and SAE(s) | Safety evaluation will include the assessment of adverse and serious adverse events over the course of the study | Approximately 8 weeks throughout the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Plaque psoriasis, PASI, BSA, sPGA, P-VAS, IL17A-, CCL20, PK