Effects of Etanercept on Nail Psoriasis and Plaque Psoriasis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate if Etanercept administered at a higher initial dose provides greater improvement in nail and skin psoriasis symptoms than a regimen with a lower initial dose.

Detailed Description
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This study will assess the effects of the 2 Etanercept regimens on fingernail psoriasis over 24 weeks among patients with both skin and fingernail symptoms who have previously failed at least one therapy for nail psoriasis. The endpoint of 24 weeks was chosen to allow sufficient time for normal nail growth.

Official Title
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Randomised, Open-label Preliminary Study to Assess the Effects of 2 Regimens of Etanercept on Nail and Skin Symptoms in Patients With Nail Psoriasis and Plaque Psoriasis

Conditions
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Nail Psoriasis, Plaque Psoriasis

Intervention / Treatment
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* Drug: etanercept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older Active, stable plaque psoriasis defined by the following criteria: Body surface area (BSA) ≥ 10 % at screening and baseline Or, PASI >10 at screening and baseline Or, PGA of Psoriasis status of moderate or worse (moderate, marked, or severe) at screening and baseline Or, DLQI > 10 at baseline Active fingernail psoriasis defined as target fingernail NAPSI ≥ 2 and overall NAPSI > 14 - Target nail is defined as the nail with the highest nail score (matrix+bed scores) at baseline. Should more than one fingernail have the same score, the target fingernail will be chosen by the investigator. Failure of at least one systemic psoriasis therapy for nail psoriasis Eligible to receive biologic therapy for psoriasis in accordance to local guidelines Exclusion Criteria: Evidence of Skin conditions other than psoriasis Psoralen plus ultraviolet radiation (PUVA), cyclosporine, alefacept, methotrexate, acitretin, or any other systemic anti-psoriasis therapy within 28 days of study drug initiation Prior exposure to any TNF-inhibitor. Prior exposure to efalizumab

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: 1<br>etanercept 50 mg SC injection twice weekly for 12 weeks reducing to etanercept 50 mg once weekly to week 24 | Drug: etanercept<br>* Subjects randomized to Arm 1 shall be treated with ETN 50 mg twice weekly for 12 weeks reducing thereafter to ETN 50 mg once weekly to 24 weeks. Subjects randomized to Arm 2 shall be treated with ETN 50 mg once weekly for the entire 24 week treatment period.<br>|
| Active Comparator: 2<br>etanercept 50 mg SC once weekly for the complete 24 week treatment period | Drug: etanercept<br>* Subjects randomized to Arm 1 shall be treated with ETN 50 mg twice weekly for 12 weeks reducing thereafter to ETN 50 mg once weekly to 24 weeks. Subjects randomized to Arm 2 shall be treated with ETN 50 mg once weekly for the entire 24 week treatment period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Nail Psoriasis Severity Index (NAPSI) Score for Target Fingernail | Target fingernail (highest matrix + bed scores at baseline) divided with imaginary lines into quadrants and graded for nail matrix and nail bed psoriasis. Sum of scores = total score for that nail (0-8). Nail Matrix Psoriasis = pitting, leukonychia, red spots in lunula, and/or nail plate crumbling. Nail Bed Psoriasis = onycholysis, splinter hemorrhages, oil drop (salmon patch) discoloration, and/or nail bed hyperkeratosis. Range for both scores: 0 (none), 1 (present in 1/4 nail), 2 (present in 2/4 nail), 3 (present in 3/4 nail), 4 (present in 4/4 nail). Higher scores = more severe psoriasis. | Baseline, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Overall Nail Psoriasis Severity Index (NAPSI) Score | NAPSI (matrix + bed score) performed on dorsal views of 8 fingers, excluding thumb; range: 0 to 8. Overall NAPSI score = sum of all fingernail scores; range: 0 to 64. Nails were divided into quadrants and graded for nail matrix and bed psoriasis. Nail Matrix Psoriasis = pitting, leukonychia, red spots in lunula, and/or nail plate crumbling. Nail Bed Psoriasis = onycholysis, splinter hemorrhages, oil drop (salmon patch) discoloration, and/or nail bed hyperkeratosis. Range for both scores: 0 (none), 1 (present 1/4 nail), 2 (present 2/4 nail), 3 (present 3/4 nail), and 4 (present 4/4 nail). | Baseline, Week 24 | 
| Percent of Participants Who Achieved a 50% Improvement in the Nail Psoriasis Severity Index (NAPSI) Score for Target Fingernail at Week 12 and Week 24 | Target fingernail (highest matrix + bed scores at baseline) divided with imaginary lines into quadrants and graded for nail matrix and nail bed psoriasis. Sum of scores = total score for that nail (0-8). Nail Matrix Psoriasis = pitting, leukonychia, red spots in lunula, and/or nail plate crumbling. Nail Bed Psoriasis = onycholysis, splinter hemorrhages, oil drop (salmon patch) discoloration, and/or nail bed hyperkeratosis. Range for both scores 0-8: 0 (none), 1 (present in 1/4 nail), 2 (present in 2/4 nail), 3 (present in 3/4 nail),4 (present in 4/4 nail). Higher score = more severe psoriasis. | Week 12, Week 24 | 
| Percent of Participants Who Achieved a 75% Improvement in the Nail Psoriasis Severity Index (NAPSI) Score for Target Fingernail at Week 12 and Week 24 | Target fingernail (highest matrix + bed scores at baseline) divided with imaginary lines into quadrants and graded for nail matrix and nail bed psoriasis. Sum of scores = total score for that nail (0-8). Nail Matrix Psoriasis = pitting, leukonychia, red spots in lunula, and/or nail plate crumbling. Nail Bed Psoriasis = onycholysis, splinter hemorrhages, oil drop (salmon patch) discoloration, and/or nail bed hyperkeratosis. Range for both scores: 0 (none), 1 (present in 1/4 nail), 2 (present in 2/4 nail), 3 (present in 3/4 nail), 4 (present in 4/4 nail). Higher scores = more severe psoriasis. | Week 12, Week 24 | 
| Percent of Participants Who Achieved a 50% Improvement in the Nail Psoriasis Severity Index (NAPSI) for Overall NAPSI Score at Week 12 and Week 24 | NAPSI (matrix + bed score) performed on dorsal views of 8 fingers, excluding thumb; range: 0 to 8. Overall NAPSI score = sum of all fingernail scores; range: 0 to 64. Nails were divided into quadrants and graded for nail matrix and bed psoriasis. Nail Matrix Psoriasis = pitting, leukonychia, red spots in lunula, and/or nail plate crumbling. Nail Bed Psoriasis = onycholysis, splinter hemorrhages, oil drop (salmon patch) discoloration, and/or nail bed hyperkeratosis. Range for both scores: 0 (none), 1 (present 1/4 nail), 2 (present 2/4 nail), 3 (present 3/4 nail), and 4 (present 4/4 nail). | Week 12, Week 24 | 
| Percent of Participants Who Achieved a 75% Improvement in the Nail Psoriasis Severity Index (NAPSI) for Overall NAPSI Score at Week 12 and Week 24 | NAPSI (matrix + bed score) performed on dorsal views of 8 fingers, excluding thumb; range: 0 to 8. Overall NAPSI score = sum of all fingernail scores; range: 0 to 64. Nails were divided into quadrants and graded for nail matrix and bed psoriasis. Nail Matrix Psoriasis = pitting, leukonychia, red spots in lunula, and/or nail plate crumbling. Nail Bed Psoriasis = onycholysis, splinter hemorrhages, oil drop (salmon patch) discoloration, and/or nail bed hyperkeratosis. Range for both scores: 0 (none), 1 (present 1/4 nail), 2 (present 2/4 nail), 3 (present 3/4 nail), and 4 (present 4/4 nail). | Week 12, Week 24 | 
| Change From Baseline in the Psoriasis Area and Severity Index (PASI) 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 was scored by itself and scores were combined for final PASI. For each section percent (%) area of skin involved was estimated: 0 (0%) to 6 (90 - 100%), and severity was estimated by clinical signs: erythema, induration, and desquamation; scale: 0 (none) to 4 (maximum). 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). | Baseline, Week 24 | 
| Percent of Participants Achieving a 50% Improvement in the Psoriasis Area and Severity Index (PASI) Score at Week 12 and 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 was scored by itself and scores were combined for final PASI. For each section percent (%) area of skin involved was estimated: 0 (0%) to 6 (90 - 100%), and severity was estimated by clinical signs: erythema, induration, and desquamation; scale: 0 (none) to 4 (maximum). 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 12 , Week 24 | 
| Percent of Participants Achieving a 75% Improvement in the Psoriasis Area and Severity Index (PASI) Score at Week 12 and 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 was scored by itself and scores were combined for final PASI. For each section percent (%) area of skin involved was estimated: 0 (0%) to 6 (90 - 100%), and severity was estimated by clinical signs: erythema, induration, and desquamation; scale: 0 (none) to 4 (maximum). 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 12 , Week 24 | 
| Change From Baseline in Physician Global Assessment (PGA) of Psoriasis | Physician Global Assessment (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. | Baseline, Week 24 | 
| Percent of Participants Achieving a Status on the Physician Global Assessment (PGA) of Psoriasis of Clear or Almost Clear | Physician Global Assessment (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, Week 24 or Early Termination | 
| Percent of Participants Achieving a Status on the Physician Global Assessment (PGA) of Psoriasis of Mild or Better | Physician Global Assessment (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 mild or better = PGA score of ≤ 2 (mild plaque elevation, mild scaling, and light red coloration). | Baseline, Week 24 or Early Termination | 
| Change From Baseline in the Dermatology Life Quality Index (DLQI) | Self-administered questionnaire to measure health-related quality of life (QoL)of adult patients suffering from skin disease; 10 questions concerning patients' perception of impact of their disease over last week encompassing aspects such as symptoms, feelings, daily activities, leisure, work, school, personal relationships and side effects of treatment. Questions scored on a 4-point Likert scale: 0 (not at all/not relevant), 1 (a little), 2 (a lot), and 3 (very much). Scores of individual items (0-3) were added to yield a total score (0-30); higher score = greater impairment of patient's QoL. | Baseline, Week 24 | 
| Change From Baseline in Physician Assessment of Nail Psoriasis Activity Visual Analog Scale (VAS) | Physician global assessment of disease activity using a visual analog scale; range: 0 (no nail disease) to 100 (worst possible nail disease). | Baseline, Week 24 | 
| Change From Baseline in Patient Assessment of Nail Psoriasis Activity Visual Analog Scale (VAS) | Patient global assessment of disease activity using a visual analog scale; range: 0 (no nail disease) to 100 (worst possible nail disease). | Baseline, Week 24 | 
| Change From Baseline in Physician Fingernail Grading Assessment Total Score | Physician assessment of disease activity for each fingernail; range: 0 (no disease), 1 (mild disease, 2 (moderate disease), or 3 (severe disease). Total score range = 0-30. | Baseline, Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nail Psoriasis, Plaque Psoriasis