Study of Icotinib Hydrochloride Cream in Patients With Mild to Moderate Psoriasis

Study Overview
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Brief Summary
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This is a phase II study to evaluate the efficacy and safety of Icotinib Hydrochloride Cream in patients with mild to moderate psoriasis.

Detailed Description
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Icotinib Hydrochloride is an oral, small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, which has been approved for treating advanced non-small cell lung cancer (NSCLC) in China. Over-expressions of EGFR and its downstream signaling proteins are implicated in the pathogenesis of psoriasis and TKIs have been considered as potential antipsoriatic agents. Icotinib hydrochloride is being developed as a cream for the treatment of mild to moderate psoriasis. This is a multicenter , randomized, doubleblind, four-arm parallel-group, placebo-controlled phase II study to assess the efficacy and safety of icotinib hydrochloride cream (1.0%, 2.0%, 4.0%) in patients with mild to moderate psoriasis. Approximately 260 subjects will be enrolled.

Official Title
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A Multicenter, Randomized, Double-blind, Four-Arm Parallel-Group, Placebo-Controlled Phase II Study to Evaluate the Efficacy and Safety of Icotinib Hydrochloride Cream in Patients With Mild to Moderate Psoriasis

Conditions
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Mild to Moderate Psoriasis

Intervention / Treatment
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* Drug: Icotinib hydrochloride cream
* Drug: Placebo cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosed plaque psoriasis for at least six months with multiple treatable areas (i.e. the lesion should not only on the face, scalp, genitals or skinfolds) which covers less than 10% of the total Body Surface Area (BSA), and affected area on the limb and/or trunk ≥ 1% BSA. The long diameter and thickness of target plaque psoriasis was ≥ 2cm and ≥2, respectively. In good health condition, with no history of diseases of major organs and no abnormality found on physical examination and vital signs. Men and women of childbearing potential must agree to use a contraceptive regimen agreed by the doctor during the trial. Female subjects that are on hormonal contraceptives must continue using the same hormonal contraceptive as that was used in the past 3 months, with the same route of administration and the same dose during the whole study. Have signed a written informed consent before entering the study. Exclusion Criteria: Psoriasis guttata, psoriasis punctata, erythrodermic psoriasis, pustular psoriasis, psoriasis arthritis. Evidence of skin conditions other than psoriasis that would interfere with evaluations of the effect of study medication on psoriasis. Drug-induced psoriasis. Present with or had historical interstitial lung disease. In the opinion of the investigator, the subjects were not considered appropriate candidates.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>65 patients with mild to moderate psoriasis will be randomized to receive 1% Icotinib hydrochloride cream, applied twice daily for 12 consecutive weeks. The drug will be applied topically to the psoriasis site. | Drug: Icotinib hydrochloride cream<br>* Apply topically twice daily for 12 consecutive weeks<br>* Other names: no other name;|
| Experimental: Cohort 2<br>65 patients with mild to moderate psoriasis will be randomized to receive 2% Icotinib hydrochloride cream, applied twice daily for 12 consecutive weeks. The drug will be applied topically to the psoriasis site. | Drug: Icotinib hydrochloride cream<br>* Apply topically twice daily for 12 consecutive weeks<br>* Other names: no other name;|
| Experimental: Cohort 3<br>65 patients with mild to moderate psoriasis will be randomized to receive 4% Icotinib hydrochloride cream, applied twice daily for 12 consecutive weeks. The drug will be applied topically to the psoriasis site. | Drug: Icotinib hydrochloride cream<br>* Apply topically twice daily for 12 consecutive weeks<br>* Other names: no other name;|
| Placebo Comparator: Cohort 4<br>65 patients with mild to moderate psoriasis will be randomized to receive placebo cream (blank cream containing no icotinib hydrochloride), applied twice daily for 12 consecutive weeks. The drug will be applied topically to the psoriasis site. | Drug: Placebo cream<br>* Apply topically twice daily for 12 consecutive weeks<br>* Other names: no other name;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants achieving a 50% improvement from baseline in psoriasis area and severity index (PASI 50) score at week 8 | PASI: Combined assessment of lesion area and severity affected into single score. The body was divided into four sections [head (10% of a person's total skin); arms (20%); trunk (30%); legs (40%)]. For each section, the area of skin involved was scored from 0 (0%) to 6 (90-100%), and the severity of skin involved was estimated by clinical signs (erythema, induration, and desquamation) to score from 0 (none) to 4 (maximum). Final PASI = Sum of severity score for each section * area score * weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4). PASI 50 represents the percentage (or number) of patients who have achieved a 50% or more reduction in their PASI score from baseline. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PASI 50 score at each visit through week 12 (except week 8) | PASI: Combined assessment of lesion area and severity affected into single score. The body was divided into four sections [head (10% of a person's total skin); arms (20%); trunk (30%); legs (40%)]. For each section, the area of skin involved was scored from 0 (0%) to 6 (90-100%), and the severity of skin involved was estimated by clinical signs (erythema, induration, and desquamation) to score from 0 (none) to 4 (maximum). Final PASI = Sum of severity score for each section * area score * weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4). PASI 50 represents the percentage (or number) of patients who have achieved a 50% or more reduction in their PASI score from baseline. | Baseline to week 12 (except week 8) | 
| Percentage of participants achieving a 75% improvement from baseline in psoriasis area and severity index (PASI 75) score at each visit through week 12 | PASI: Combined assessment of lesion area and severity affected into single score. The body was divided into four sections [head (10% of a person's total skin); arms (20%); trunk (30%); legs (40%)]. For each section, the area of skin involved was scored from 0 (0%) to 6 (90-100%), and the severity of skin involved was estimated by clinical signs (erythema, induration, and desquamation) to score from 0 (none) to 4 (maximum). Final PASI = Sum of severity score for each section * area score * weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4). PASI 75 represents the percentage (or number) of patients who have achieved a 75% or more reduction in their PASI score from baseline. | Baseline to week 12 | 
| Change PASI score at each visit from baseline through week 12 | PASI: Combined assessment of lesion area and severity affected into single score. The body was divided into four sections [head (10% of a person's total skin); arms (20%); trunk (30%); legs (40%)]. For each section, the area of skin involved was scored from 0 (0%) to 6 (90-100%), and the severity of skin involved was estimated by clinical signs (erythema, induration, and desquamation) to score from 0 (none) to 4 (maximum). Final PASI = Sum of severity score for each section * area score * weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4). | Baseline to week 12 | 
| Percentage of participants achieving the physician global assessment (PGA) of psoriasis responses of clear (0) or almost clear (1) and ≥2 grade improvement at each visit through week 12 | PGA of Psoriasis: score based on dermatologist's assessment of skin disease averaged over all lesions. Overall lesions were graded for induration, erythema, and scaling; range: 0 (no evidence) to 5 (severe). Higher scores indicate greater severity of disease. | Baseline to week 12 | 
| Lesion severity | Lesion severity includes the sum of 3 indications, e.g. Erythema, scaling, thickness of target psoriasis site on patients with mild to moderate psoriasis. Each indication is scored from 0 (not at all serious) to 4 (very serious). | Baseline to week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EGFR inhibitor, topical agent, psoriasis, phase 2