Phase II Study Evaluating the Clinical Efficacy and Safety of GN-037 in Plaque Psoriasis

Study Overview
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Brief Summary
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This Phase II study was designed as a multicenter, randomized, double-blind, placebo-controlled and 3-parallel arm, to assess clinical efficacy, safety, and tolerability of GN-037 versus clobetasol 17-propionate and placebo in patients diagnosed with mild to moderate plaque psoriasis at least 6 months ago

Detailed Description
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A total of 190 patients aged between 18-65 years diagnosed with plaque psoriasis are planned to be included in the study. The study consists of three periods: Screening period: Within 4 weeks before baseline visit (-28 days to 0 days) Treatment period: 4 weeks Follow-up period with observation: 4 weeks The study is planned to last a maximum of 12 weeks for each patient. Study consists of 5 visits: baseline (day 1), week 2, week 4, week 6 and week 8 which is a follow-up period with observation.

Official Title
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A Multicenter Randomized Double-blind Placebo-controlled Parallel Group Phase II Study Evaluating the Clinical Efficacy and Safety of GN-037 Cream Used in the Treatment of Mild to Moderate Plaque Psoriasis

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: GN-037
* Drug: Clobetasol 17-propionate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients between the ages of 18-65 Patients who can give their written informed consent prior to initiating any evaluation or procedure related to the study. Patients with negative SARS-CoV-2 PCR test result Patients who were diagnosed with mild or moderate plaque psoriasis at least 6 months ago by a dermatologist and whose diagnosis was confirmed according to the clinical judgment of the research physician at the time of enrolment. Patients with a Investigator Global Assessment (IGA) score of 3 or 4 at the screening visit [Face, scalp, palms, soles, armpits, and intertriginous areas will be excluded from this assessment] Patients with plaque psoriasis lesions covering a body surface area (BSA) of at least 3% to 12% [Face, scalp, palms, soles, axillae, and intertriginous areas will be excluded from this assessment.] Patients who received the last psoriasis treatment 4 weeks or before Patients who are confirmed to be healthy by medical history and physical examination and who do not have any clinically significant disease/condition other than plaque psoriasis that, at the discretion of the investigator, could affect the study evaluation. Patients who can protect the lesion areas from ultraviolet (UV) rays (natural or artificial) during the study Female patients: Patients who had a negative pregnancy test at the screening visit, did not breastfeed, did not plan pregnancy during the study, and agreed to use an effective method of contraception until the end of the study. Male patients: Patients who agreed to use an effective method of contraception for the duration of the study. Patients who can comply with all scheduled visits, laboratory tests, and other study procedures Patients with normal adrenocorticotropic hormone (ACTH) stimulation test Patients with normal dihydroepiandrostenedione sulfate (DHEAS) levels Exclusion Criteria: Patients with a known sensitivity/hypersensitivity to any component of the drugs to be used in the study Pregnant or lactating or female patients with a positive pregnancy test Patients who are resistant/unresponsive to corticosteroids Patients with psoriasis (eg guttate, erythrodermic, exfoliative or pustular) that, in the opinion of the investigating physician, resolves spontaneously or rapidly worsens Patients with other inflammatory skin disease (eg, atopic dermatitis, contact dermatitis, eczema, tinea corporis) that, in the opinion of the investigative physician, may affect study evaluations at the targeted treatment sites Patients who received phototherapy, photochemotherapy, systemic or local treatment for psoriasis or used systemic anti-inflammatory agents in the last 4 weeks Patients who received biologic therapy for psoriasis in the last 3 months Immunosuppressive or immunocompromised patients (patients who have taken immunosuppressive drugs in the last 2 months will also be excluded) Patients who have received any cancer treatment in the last 1 year Patients with severe hypertension (systolic blood pressure [SBP] > 160 mmHg or diastolic blood pressure [DBP] > 100 mmHg) Patients who cannot comply with the study procedures/rules and cannot be in harmony with the research team Patients who have participated in another clinical trial in the last 2 months or who are taking part in another clinical trial concurrently Patients with a known abnormality of the hypothalamus-pituitary-adrenal axis (HPA axis) Patients using products containing dihydroepiandrostenedione (DHEA) or dihydroepiandrostenedione sulfate (DHEAS) in the last 1 month

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GN-037 cream<br>Psoriatic patients will receive GN-037 cream in 2:2:1 ratio Psoriatic patients will receive GN-037 cream twice daily on a selected body target lesion GN-037 cream will be applied as a thin film layer for 4 weeks. | Drug: GN-037<br>* GN-037<br>|
| Active Comparator: Clobetasol 17-propionate cream<br>Clobetasol 17-propionate cream will be applied in 2:2:1 ratio Psoriatic patients will receive clobetasol 17-propionate cream twice daily on a selected body target lesion Clobetasol 17-propionate will be applied as a thin film layer for 4 weeks. | Drug: Clobetasol 17-propionate<br>* Clobetasol 17-propionate<br>|
| Placebo Comparator: Placebo<br>Placebo cream will be applied in 2:2:1 ratio Psoriatic patients will receive placebo cream twice daily on a selected body target lesion Placebo cream will be applied as a thin film layer for 4 weeks. | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in Investigator Global Assessment (IGA) score evaluated at weeks 2, 4, 6 and 8 in each arm. | Improvement will be evaluated as the number and percent of patients with at least 2 points improvement in IGA score, and IGA score equating to 0 or 1. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in %BSA affected from baseline at weeks 2, 4, 6 and 8 in each arm. | Target plaque area (cm2) was determined by multiplying the longest diameter (cm) of the target plaque by the widest perpendicular diameter (cm). A negative percent change indicates a mild disease. | 28 days | 
| Improvement in Psoriasis Area Severity Index (PASI) from baseline at weeks 2, 4, 6 and 8 in each arm. Improvement will be evaluated as the number and percent of patients with ≥75% improvement in PASI score. | The PASI scoring system takes into account the overall severity of erythema (redness), induration (plaque thickness) and scaling, and the extent of %Body Surface Area affected with psoriasis. Higher scores indicate more severe disease. PASI is a static assessment made without reference to previous scores. | 28 days | 
| Mean change in in total plaque severity score (TPSS) from baseline at week 2, 4, 6 and 8 in each arm. | For TPSS, all target lesions were scored individually for signs of induration, scaling, and erythema using a 5-point severity scale: 0 = none; 1 = mild; 2 = moderate; 3 = severe; 4 = very severe. A negative percent change indicates better outcome. | 28 days | 
| Improvement in target lesion healing from baseline at weeks 2, 4, 6 and 8 in each arm. | Improvement will be evaluated as the number and percent of patients whose target lesion erythema, plaque thickness and scaling score improvement at least 2 points at week 2, 4, 6 and 8 compared to baseline in each arm. Additionally, at which week at least 50% improvement in the target lesion healing is observed in each arm will be evaluated. Target plaque area (cm2) was determined by multiplying the longest diameter (cm) of the target plaque by the widest perpendicular diameter (cm). | .28 days | 
| Improvement in Dermatology Life Quality Index (DLQI) | Improvement in DLQI at week 8 compared to baseline. | 28 days | 
| Safety, Adverse Events and Serious Adverse Events | Safety will be evaluated as the number and ratio of patients with adverse events and serious adverse events in each arm. Additionally, number of adverse events which resulted in discontinuation of the study treatment in each arm will be evaluated | 56 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mild to moderate plaque psoriasis, local treatment