Study Evaluating the Efficacy and Safety of Etanercept and Acitretin in Korean Patient With Moderate to Severe Psoriasis

Study Overview
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Brief Summary
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To compare the efficacy of ETN 50mg twice weekly for 12 weeks followed by reduction to a maintenance dose of 25mg twice weekly at week 24 with that of combination of ETN 25 mg Twice Weekly plus Acitretin 10mg BID at week 24 in subjects with moderate to severe psoriasis.

Official Title
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A Multicenter, Randomized, Open Pilot Trial Assessing the Efficacy and Safety of Etanercept 50 mg Twice Weekly Followed Etanercept 25mg Twice Weekly, the Combination of Etanercept 25 mg Twice Weekly and Acitretin and Acitretin Alone in Patients With Moderate to Severe Psoriasis

Conditions
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Moderate to Severe Psoriasis

Intervention / Treatment
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* Drug: Etanercept
* Drug: Etanercept + Acitretin
* Drug: Acitretin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Active, moderate to severe psoriasis defined by the following criteria: Clinically stable, plaque psoriasis involving more than 10% body surface area (BSA) or PASI 10. In the opinion of the investigator, failure, intolerance, contraindication or not a candidate for the following: Methotrexate (MTX), cyclosporine, and psoralen plus ultraviolet A radiation (PUVA) therapy. Negative urine pregnancy test before the first dose of study drug in all female patients Exclusion Criteria: Evidence of skin conditions (e.g., eczema) other than psoriasis that would interfere with evaluations of the effect of study medication on psoriasis. Any rheumatologic disease such as rheumatoid arthritis, psoriatic arthritis, gout, systemic lupus erythematous, systemic vasculitis, scleroderma and polymyositis, or associated syndromes. Prior exposure to TNF inhibitors including ETN. Prior exposure to efalizumab (Raptiva®) and alefacept (Amevive®) is also prohibited.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A<br> | Drug: Etanercept<br>* Etanercept at a dose of 50mg twice weekly for 12 weeks followed by 25mg twice weekly for 12 weeks<br>* Other names: Etanercept 50mg followed by 25mg;|
| Experimental: Group B<br> | Drug: Etanercept + Acitretin<br>* Combination of etanercept at a dose of 25mg twice weekly and acitretin 10mg BID for 24 weeks<br>* Other names: Etancercept 25mg and Acitretin 10mg;|
| Active Comparator: Group C<br> | Drug: Acitretin<br>* Acitretin at a dose of 10mg BID for 24 weeks<br>* Other names: Acitretin 10mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving a 75 Percent (%) Improvement in Psoriasis Area and Severity Index (PASI 75) Score at Week 24 | Combined assessment of lesion severity and area affected into single score; range: 0 (no disease) to 72 (maximal disease). Body was divided into 4 sections (head, arms, trunk, legs); each area scored by itself and scores combined for final PASI. For each section, area of skin involved was estimated: 0 (0%) to 6 (90 - 100%), and severity estimated by clinical signs: erythema, induration, and desquamation; scale: 0 (none) to 4 (exceptionally striking). Final PASI = sum of severity parameters for each section * area score * weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4). | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving a 50% Improvement in Psoriasis Area and Severity Index (PASI 50) Score | Combined assessment of lesion severity and area affected into single score; range: 0 (no disease) to 72 (maximal disease). Body was divided into 4 sections (head, arms, trunk, legs); each area scored by itself and scores combined for final PASI. For each section, area of skin involved was estimated: 0 (0%) to 6 (90 - 100%), and severity estimated by clinical signs: erythema, induration, and desquamation; scale: 0 (none) to 4 (exceptionally striking). Final PASI = sum of severity parameters for each section * area score * weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4). | Weeks 2, 4, 8, 12, 18, and 24 | 
| Percentage of Participants Achieving a Status on the Physician Global Assessment (PGA) of Psoriasis of Clear | PGA of Psoriasis: score based on dermatologist's assessment of disease averaged over all lesions of head, scalp, and neck. Overall lesions were graded for induration, erythema, and scaling; range: 0 (no evidence) to 5 (severe). The sum of the 3 scores was divided by 3 to obtain a final PGA score. Higher scores indicate greater severity of disease. Assessment of clear = PGA score of 0 (no evidence). | Baseline, Weeks 2, 4, 8, 12, 18 and 24 | 
| Percentage of Participants Achieving a Status on the PGA of Psoriasis of Clear or Almost Clear | PGA of Psoriasis: score based on dermatologist's assessment of disease averaged over all lesions of head, scalp, and neck. Overall lesions were graded for induration, erythema, and scaling; range: 0 (no evidence) to 5 (severe). The sum of the 3 scores was divided by 3 to obtain a final PGA score. Higher scores indicate greater severity of disease. Assessment of clear or almost clear = PGA score of 0 (no evidence), or 1 (minimal/faint). | Baseline, Weeks 2, 4, 8, 12, 18 and 24 | 
| Percentage of Participants Achieving a Status on the PGA of Psoriasis of Clear or Almost Clear or Mild | PGA of Psoriasis: score based on dermatologist's assessment of disease averaged over all lesions of head, scalp, and neck. Overall lesions were graded for induration, erythema, and scaling; range: 0 (no evidence) to 5 (severe). The sum of the 3 scores was divided by 3 to obtain a final PGA score. Higher scores indicate greater severity of disease. Assessment of clear or almost clear or mild = PGA score of 0 (no evidence), 1 (minimal/faint), 2 (mild). | Baseline, Weeks 2, 4, 8, 12, 18 and 24 | 
| Time to Achieve a PASI 50 Score | PASI 50 defined as a 50% or greater improvement in PASI score from Baseline | Baseline up to Week 24 | 
| Time to Achieve a PASI 75 Score | PASI 75 defined as a 75% or greater improvement in PASI score from Baseline | Baseline up to Week 24 | 
| Time to Achieve a Status on the PGA of Psoriasis of Clear or Almost Clear or Mild | PGA of Psoriasis: score based on dermatologist's assessment of disease averaged over all lesions of head, scalp, and neck. Overall lesions were graded for induration, erythema, and scaling; range: 0 (no evidence) to 5 (severe). The sum of the 3 scores was divided by 3 to obtain a final PGA score. Higher scores indicate greater severity of disease. Assessment of clear or almost clear or mild = PGA score of 0 (no evidence), 1 (minimal/faint), or 2 (mild). | Baseline up to Week 24 | 
| Time to Achieve a Status on the PGA of Psoriasis of Clear or Almost Clear | PGA of Psoriasis: score based on dermatologist's assessment of disease averaged over all lesions of head, scalp, and neck. Overall lesions were graded for induration, erythema, and scaling; range: 0 (no evidence) to 5 (severe). The sum of the 3 scores was divided by 3 to obtain a final PGA score. Higher scores indicate greater severity of disease. Assessment of clear or almost clear = PGA score of 0 (no evidence), or 1 (minimal/faint). | Baseline up to Week 24 | 
| Change From Baseline in the PGA of Psoriasis | PGA of Psoriasis: score based on dermatologist's assessment of disease averaged over all lesions of head, scalp, and neck. Overall lesions were graded for induration, erythema, and scaling; range: 0 (no evidence) to 5 (severe). The sum of the 3 scores was divided by 3 to obtain a final PGA score. Higher scores indicate greater severity of disease. Assessment of clear = PGA score of 0 (no evidence). Change = Week x, minus Baseline, where smaller scores indicate improvement. | Baseline, Weeks 2, 4, 8, 12, 18, and 24 | 
| Change From Baseline in the PASI Score | Combined assessment of lesion severity, area affected into single score; range:0(no disease) to 72(maximal disease).Body divided into 4 sections (head, arms, trunk, legs); each area scored by itself and scores combined for final PASI. For each section, area of skin involved was estimated:0(0%) to 6(90-100%), severity estimated by clinical signs: erythema, induration, desquamation; scale: 0(none) to 4(maximum). Final PASI = sum of severity parameters for each section * area score * weight of section(head:0.1,arm:0.2,body: 0.3, leg:0.4). Change=Week X-Baseline, smaller scores show improvement. | Baseline, Weeks 2, 4, 8, 12, 18 and 24 | 
| Change From Baseline in Percent Body Surface Area (BSA) Involvement of Psoriasis at Weeks 2, 4, 8, 12, 18 and 24 | Change from Baseline in the percentage of the surface area of the body affected by psoriasis. Change = Week x minus Baseline, where smaller scores indicate improvement. | Baseline, Weeks 2, 4, 8, 12, 18 and 24 | 
| Change From Baseline in Subject Global Assessment (SGA) of Joint Pain at Weeks 2, 4, 8, 12 ,18 and 24 | Participants were asked to rate the severity of their joint pain on a 6-point scale, where 0=good and 5=severe. Change = Week X minus Baseline, where smaller scores indicate improvement. | Baseline, Weeks 2, 4, 8, 12, 18 and 24 | 
| Change From Baseline in SGA of Psoriasis at Weeks 2, 4, 8, 12 ,18 and 24 | Participants were asked to rate the severity of their psoriasis disease activity on a 6-point scale, where 0=good and 5=severe. Change = Week X minus Baseline, where smaller scores indicate improvement. | Baseline, Weeks 2, 4, 8, 12 ,18 and 24 | 
| Change From Baseline in SGA of Itching at Each Visit | Participants were asked to rate the severity of their psoriasis itching on a 6-point scale, where 0=good and 5=severe. Change = Week X minus Baseline, where smaller scores indicate improvement. | Baseline, Weeks 2, 4, 8, 12 ,18 and 24 | 
| Change From Baseline in Psoriasis Subject Satisfaction Questionnaire (PSSQ) Question 1, at Weeks 2, 4, 8, 12, 18 and 24 | Participants completed a satisfaction survey at baseline and throughout the study. Participants were asked to rate, based on their experience during the past week, how satisfied or dissatisfied they were with the overall appearance of their skin. Responses were based on a 5-point scale: Very dissatisfied (0), Dissatisfied (1), Neither satisfied nor dissatisfied (2), Satisfied (3), Very satisfied (4), Never had this problem (5). Change = Week X minus Baseline, where larger scores indicate improvement. | Baseline, Weeks 2, 4, 8, 12, 18 and 24 | 
| Change From Baseline in Psoriasis Subject Satisfaction Questionnaire (PSSQ) Question 2, at Weeks 2, 4, 8, 12, 18 and 24 | Participants completed a satisfaction survey at baseline and throughout the study. Participants were asked to rate, based on their experience during the past week, how satisfied or dissatisfied they were with the treatment's effect on the flaking of their skin. Responses were based on a 5-point scale: Very dissatisfied (0), Dissatisfied (1), Neither satisfied nor dissatisfied (2), Satisfied (3), Very satisfied (4), Never had this problem (5). Change = Week X minus Baseline, where larger scores indicate improvement. | Baseline, Weeks 2, 4, 8, 12, 18 and 24 | 
| Change From Baseline in Psoriasis Subject Satisfaction Questionnaire (PSSQ) Question 3, at Weeks 2, 4, 8, 12, 18 and 24 | Participants completed a satisfaction survey at baseline and throughout the study. Participants were asked to rate, based on their experience during the past week, how satisfied or dissatisfied they were with the treatment's effect on the redness of their skin. Responses were based on a 5-point scale: Very dissatisfied (0), Dissatisfied (1), Neither satisfied nor dissatisfied (2), Satisfied (3), Very satisfied (4), Never had this problem (5). Change = Week X minus Baseline, where larger scores indicate improvement. | Baseline, Weeks 2, 4, 8, 12, 18 and 24 | 
| Change From Baseline in Psoriasis Subject Satisfaction Questionnaire (PSSQ) Question 4, at Weeks 2, 4, 8, 12, 18 and 24 | Participants completed a satisfaction survey at baseline and throughout the study. Participants were asked to rate, based on their experience during the past week, how satisfied or dissatisfied they were with the treatment's effect on tightness in the skin. Responses were based on a 5-point scale: Very dissatisfied (0), Dissatisfied (1), Neither satisfied nor dissatisfied (2), Satisfied (3), Very satisfied (4), Never had this problem (5). Change = Week X minus Baseline, where larger scores indicate improvement. | Baseline, Weeks 2, 4, 8, 12, 18 and 24 | 
| Change From Baseline in Psoriasis Subject Satisfaction Questionnaire (PSSQ) Question 5, at Weeks 2, 4, 8, 12, 18 and 24 | Participants completed a satisfaction survey at baseline and throughout the study. Participants were asked to rate, based on their experience during the past week, how satisfied or dissatisfied they were with the treatment's effect on bleeding of the skin. Responses were based on a 5-point scale: Very dissatisfied (0), Dissatisfied (1), Neither satisfied nor dissatisfied (2), Satisfied (3), Very satisfied (4), Never had this problem (5). Change = Week X minus Baseline, where larger scores indicate improvement. | Baseline, Weeks 2, 4, 8, 12, 18 and 24 | 
| Change From Baseline in Psoriasis Subject Satisfaction Questionnaire (PSSQ) Question 6, at Weeks 2, 4, 8, 12, 18 and 24 | Participants completed a satisfaction survey at baseline and throughout the study. Participants were asked to rate, based on their experience during the past week, how satisfied or dissatisfied they were with the treatment's effect on burning sensation of the skin. Responses were based on a 5-point scale: Very dissatisfied (0), Dissatisfied (1), Neither satisfied nor dissatisfied (2), Satisfied (3), Very satisfied (4), Never had this problem (5). Change = Week X minus Baseline, where larger scores indicate improvement. | Baseline, Weeks 2, 4, 8, 12, 18 and 24 | 
| Change From Baseline in Psoriasis Subject Satisfaction Questionnaire (PSSQ) Question 7, at Weeks 2, 4, 8, 12, 18 and 24 | Participants completed a satisfaction survey at baseline and throughout the study. Participants were asked to rate, based on their experience during the past week, how satisfied or dissatisfied they were with the treatment's effect on skin pain. Responses were based on a 5-point scale: Very dissatisfied (0), Dissatisfied (1), Neither satisfied nor dissatisfied (2), Satisfied (3), Very satisfied (4), Never had this problem (5). Change = Week X minus Baseline, where larger scores indicate improvement. | Baseline, Weeks 2, 4, 8, 12, 18 and 24 | 
| Change From Baseline in Psoriasis Subject Satisfaction Questionnaire (PSSQ) Question 8, at Weeks 2, 4, 8, 12, 18 and 24 | Participants completed a satisfaction survey at baseline and throughout the study. Participants were asked to rate, based on their experience during the past week, how satisfied or dissatisfied they were with the treatment's effect on joint pain. Responses were based on a 5-point scale: Very dissatisfied (0), Dissatisfied (1), Neither satisfied nor dissatisfied (2), Satisfied (3), Very satisfied (4), Never had this problem (5). Change = Week X minus Baseline, where larger scores indicate improvement. | Baseline, Weeks 2, 4, 8, 12, 18 and 24 | 
| Change From Baseline in Psoriasis Subject Satisfaction Questionnaire (PSSQ) Question 9, at Weeks 2, 4, 8, 12, 18 and 24 | Participants completed a satisfaction survey at baseline and throughout the study. Participants were asked to rate, based on their experience during the past week, how satisfied or dissatisfied they were with the treatment's effect on their comfort level with their personal appearance. Responses were based on a 5-point scale: Very dissatisfied (0), Dissatisfied (1), Neither satisfied nor dissatisfied (2), Satisfied (3), Very satisfied (4), Never had this problem (5). Change = Week X minus Baseline, where larger scores indicate improvement. | Baseline, Weeks 2, 4, 8, 12, 18 and 24 | 
| Change From Baseline in Psoriasis Subject Satisfaction Questionnaire (PSSQ) Question 10, at Weeks 2, 4, 8, 12, 18 and 24 | Participants completed a satisfaction survey at baseline and throughout the study. Participants were asked to rate, based on their experience during the past week, how satisfied or dissatisfied they were with the treatment's effect on their anxiety. Responses were based on a 5-point scale: Very dissatisfied (0), Dissatisfied (1), Neither satisfied nor dissatisfied (2), Satisfied (3), Very satisfied (4), Never had this problem (5). Change = Week X minus Baseline, where larger scores indicate improvement. | Baseline, Weeks 2, 4, 8, 12, 18 and 24 | 
| Change From Baseline in Psoriasis Subject Satisfaction Questionnaire (PSSQ) Question 11, at Weeks 2, 4, 8, 12, 18 and 24 | Participants completed a satisfaction survey at baseline and throughout the study. Participants were asked to rate, based on their experience during the past week, how satisfied or dissatisfied they were with the treatment's effect on their depression. Responses were based on a 5-point scale: Very dissatisfied (0), Dissatisfied (1), Neither satisfied nor dissatisfied (2), Satisfied (3), Very satisfied (4), Never had this problem (5). Change = Week X minus Baseline, where larger scores indicate improvement. | Baseline, Weeks 2, 4, 8, 12, 18 and 24 | 
| Change From Baseline in Psoriasis Subject Satisfaction Questionnaire (PSSQ) Question 12, at Weeks 2, 4, 8, 12, 18 and 24 | Participants completed a satisfaction survey at baseline and throughout the study. Participants were asked to rate, based on their experience during the past week, how satisfied or dissatisfied they were with the treatment's effect on their fatigue. Responses were based on a 5-point scale: Very dissatisfied (0), Dissatisfied (1), Neither satisfied nor dissatisfied (2), Satisfied (3), Very satisfied (4), Never had this problem (5). Change = Week X minus Baseline, where larger scores indicate improvement. | Baseline, Weeks 2, 4, 8, 12, 18 and 24 | 
| Change From Baseline in Psoriasis Subject Satisfaction Questionnaire (PSSQ) Question 13, at Weeks 2, 4, 8, 12, 18 and 24 | Participants completed a satisfaction survey at baseline and throughout the study. Participants were asked to rate, based on their experience during the past week, how satisfied or dissatisfied they were with the treatment's effect on how others responded to their personal appearance at work/school. Responses were based on a 5-point scale: Very dissatisfied (0), Dissatisfied (1), Neither satisfied nor dissatisfied (2), Satisfied (3), Very satisfied (4), Never had this problem (5). Change = Week X minus Baseline, where larger scores indicate improvement. | Baseline, Weeks 2, 4, 8, 12, 18 and 24 | 
| Change From Baseline in Psoriasis Subject Satisfaction Questionnaire (PSSQ) Question 14, at Weeks 2, 4, 8, 12, 18 and 24 | Participants completed a satisfaction survey at baseline and throughout the study. Participants were asked to rate, based on their experience during the past week, how satisfied or dissatisfied they were with the treatment's effect on how their skin affected social and leisure activities. Responses were based on a 5-point scale: Very dissatisfied (0), Dissatisfied (1), Neither satisfied nor dissatisfied (2), Satisfied (3), Very satisfied (4), Never had this problem (5). Change = Week X minus Baseline, where larger scores indicate improvement. | Baseline, Weeks 2, 4, 8, 12, 18 and 24 | 
| Change From Baseline in Psoriasis Subject Satisfaction Questionnaire (PSSQ) Question 15, at Weeks 2, 4, 8, 12, 18 and 24 | Participants completed a satisfaction survey at baseline and throughout the study. Participants were asked to rate, based on their experience during the past week, how satisfied or dissatisfied they were with their psoriasis therapy in general. Responses were based on a 5-point scale: very dissatisfied (0), dissatisfied (1), neither satisfied nor dissatisfied (2), satisfied (3), very satisfied (4). Change = Week X minus Baseline, where larger scores indicate improvement. | Baseline, Weeks 2, 4, 8, 12, 18 and 24 | 
| Change From Baseline in Psoriasis Subject Satisfaction Questionnaire (PSSQ) Question 16, at Weeks 2, 4, 8, 12, 18 and 24 | Participants completed a satisfaction survey at baseline and throughout the study. Participants were asked to respond to the statement I would like to continue with my current psoriasis treatment. Responses were based on a 5-point scale: strongly disagree (0), disagree(1), neither agree nor disagree (2), agree (3), strongly agree (4). Change = Week X minus Baseline, where larger scores indicate improvement. | Baseline, Weeks 2, 4, 8, 12, 18 and 24 | 
| Change From Baseline in the Percentage of Participants Who Responded Yes to the Psoriasis Subject Satisfaction Questionnaire (PSSQ) Question 17, at Weeks 2, 4, 8, 12, 18 and 24 | Participants completed a satisfaction survey at baseline and throughout the study. Participants were asked to answer the following question with either a yes or no, Taking into account your psoriasis symptoms, the appearance of your skin and all other problems which psoriasis causes, do you consider that your current health state is satisfactory? Percentage of participants who responded yes reported. | Baseline, Weeks 2, 4, 8, 12, 18 and 24 | 
| Change From Baseline in the Percentage of Participants Who Responded Yes to Psoriasis Subject Satisfaction Questionnaire (PSSQ) Question 18, at Weeks 2, 4, 8, 12, 18 and 24 | Participants completed a satisfaction survey at baseline and throughout the study. Participants were asked to answer the following question with either a yes or no, Taking into account your psoriasis symptoms, the appearance of your skin, medicine side effects and medicine ease/difficulty of use, do you consider that your current psoriasis treatment is satisfactory? Percentage of participants who responded yes reported. | Baseline, Weeks 2, 4, 8, 12, 18 and 24 | 

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