Controlled Study of Humira in Subjects With Chronic Plaque Psoriasis of the Hands and/or Feet

Study Overview
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Brief Summary
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Evaluate the efficacy and safety of a 16-week course of Humira (adalimumab) compared to placebo in adults with chronic plaque psoriasis of the hands and/or feet and the sustainability of response for 12 additional weeks.

Official Title
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Controlled Study of Humira in Subjects With Chronic Plaque Psoriasis of the Hands and/or Feet

Conditions
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Psoriasis

Intervention / Treatment
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* Biological: Placebo
* Biological: Adalimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult with Diagnosis of chronic plaque psoriasis of the Hands and Feet for at least 6 months, with a PGA >/=3 and candidates for systemic therapy; Patients in good general health Able to self-administer injections Negative chest x-ray (CXR) and purified protein derivative (PPD) test, unless willing to start anti-tuberculosis (TB) prophylaxis Exclusion Criteria: Previous treatment with HUMIRA® Required mediation stability or washouts for: systemic corticosteroids (28 days), other investigational agent, other systemic therapies for psoriasis, ultraviolet B (UVB), psoralen with UVA (PUVA) Other active skin diseases or skin infections Diagnosis of palmoplantar pustulosis; erythrodermic psoriasis, pustular psoriasis, medication-induced or exacerbated psoriasis or new onset of guttate psoriasis Evidence of dysplasia or history of malignancy (Other than a successfully treated non-metastatic cutaneous squamous cell, basal cell carcinoma or localized carcinoma in situ of the cervix); History of listeriosis, histoplasmosis, chronic or active Hepatitis B infection, human immunodeficiency virus (HIV) infection, immunodeficiency syndrome, chronic recurring infections or active tuberculosis (TB); History of moderate to severe congestive heart failure, Recent cerebrovascular accident and any other condition which, in the opinion of the investigator, would put the subject at risk; History of central nervous system (CNS) demyelinating disease or neurologic symptoms suggestive of CNS demyelinating disease; History of clinically significant drug or alcohol abuse in the last 12 months; Infection(s) requiring treatment with intravenous (IV) antibiotics, IV antivirals, or IV antifungals within 30 days prior to Baseline or oral antibiotics, oral antivirals, or oral antifungals within 14 days prior to Baseline; Known hypersensitivity to the excipients of HUMIRA® as stated in the label; Female subjects who are pregnant or breast-feeding or considering becoming pregnant during the study. Prior exposure to Tysabri® (natalizumab)

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo/Adalimumab<br>Loading dose of 2 placebo injections at Week 0 and placebo injections every other week (eow) from Week 1 through Week 15. In second period of study, subjects who continued in the study received 80 mg adalimumab at Week 16 followed by open-label 40 mg adalimumab eow from Week 17 to Week 27. | Biological: Placebo<br>* Loading dose of 2 placebo subcutaneous (SC) injections (0.8 ml) at Week 0 followed by 1 injection SC eow from Week 1 to Week 15.In second period of study, subjects who continued in the study received 80 mg adalimumab at Week 16 followed by open-label 40 mg adalimumab eow from Week 17 to Week 27.<br>Biological: Adalimumab<br>* Loading dose of 80 mg adalimumab SC (two 40 mg injections) followed by 40 mg adalimumab SC eow.<br>* Other names: ABT-D2E7;|
| Active Comparator: Adalimumab<br>80 mg adalimumab loading dose at Week 0 and 40 mg adalimumab eow from Weeks 1 through 15. For subjects who continued in the second period of the study, subjects received 2 placebo injections at Week 16 to maintain the blind. Open-label 40 mg adalimumab eow was administered from Week 17 through Week 27. | Biological: Adalimumab<br>* Loading dose of 80 mg adalimumab SC (two 40 mg injections) followed by 40 mg adalimumab SC eow.<br>* Other names: ABT-D2E7;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Physician's Global Assessment of Psoriasis (PGA) of Clear or Almost Clear at Week 16 | Number of subjects achieving a PGA of clear (representing no signs of plaque psoriasis) or almost clear (representing just perceptible erythema and scaling) at Week 16. The PGA is a 5-point scale used to measure the severity of disease at the time of the physician's evaluation of the subject. The degree of overall severity is rated as follows: 0-Clear, 1-Almost clear, 2-Mild, 3-Moderate, and 4-Severe. | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Erythema, Scaling, Induration, and Fissuring (ESIF) | Severity of each sign of ESIF was assessed using a 4-point scale (0 = clear, 1 = mild, 2 = moderate, and 3 = severe). The ESIF was calculated by adding the scores for the 4 signs for the two soles and two palms, for a total range from 0 (no disease) to 48 points (most severe condition). A decrease from Baseline in ESIF indicates improvement. | Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 28 | 
| Mean Change From Baseline in ESIF for Palms | Severity of each sign of ESIF was assessed using a 4-point scale (0 = clear, 1 = mild, 2 = moderate, and 3 = severe). The ESIF was calculated by adding the scores for the 4 signs for the palms of the hands, yielding a total range from 0 (no disease) to 24 points (most severe condition) for the palms. A decrease from Baseline in ESIF indicates improvement. | Baseline and Weeks 2, 4, 12, 16, 20, 24, and 28 | 
| Mean Change From Baseline in ESIF for Soles | Severity of each sign of ESIF was assessed using a 4-point scale (0 = clear, 1 = mild, 2 = moderate, and 3 = severe). The ESIF was calculated by adding the scores for the 4 signs for the soles of the feet, yielding a total range from 0 (no disease) to 24 points (most severe condition) for the soles. A decrease from Baseline in ESIF indicates improvement. | Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 28 | 
| Number of Subjects With Moderate Improvement in ESIF From Baseline | Number of subjects that achieved > 50% reduction from Baseline in ESIF. | Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 28 | 
| Number of Subjects With Marked Improvement in ESIF From Baseline | Number of subjects that achieved > 75% reduction from Baseline in ESIF | Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 28 | 
| Mean Change From Baseline in Nail Psoriasis Severity Index (NAPSI) | For subjects with psoriasis nail involvement at Baseline, the target fingernail (most severely involved fingernail at Baseline) was assessed for NAPSI throughout the study. NAPSI ranges from 0 (no nail psoriasis) to 8 (most severe nail psoriasis). | Baseline and Weeks 8, 16, and 28 | 
| Number of Subjects With Physicians Global Assessment of Psoriasis (PGA) of Clear, Almost Clear, or Mild | Number of subjects achieving a PGA of clear (representing no signs of plaque psoriasis), almost clear (representing just perceptible erythema and scaling), or mild (representing light pink erythema with minimal scaling and with or without pustules). The PGA is a 5-point scale used to measure the severity of disease at the time of the physician's evaluation of the subject. The degree of overall severity is rated as follows: 0-Clear, 1-Almost clear, 2-Mild, 3-Moderate, and 4-Severe. | Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, and 28 | 
| Number of Subjects With PGA of Clear or Almost Clear | Number of subjects achieving a PGA of clear (representing no signs of plaque psoriasis) or almost clear (representing just perceptible erythema and scaling). The PGA is a 5-point scale used to measure the severity of disease at the time of the physician's evaluation of the subject. The degree of overall severity is rated as follows: 0-Clear, 1-Almost clear, 2-Mild, 3-Moderate, and 4-Severe. | Baseline and Weeks 2, 4, 8, 12, 20, 24, and 28 | 
| Number of Subjects With PGA of Clear | Number of subjects achieving a PGA of clear (representing no signs of plaque psoriasis). The PGA is a 5-point scale used to measure the severity of disease at the time of the physician's evaluation of the subject. The degree of overall severity is rated as follows: 0-Clear, 1-Almost clear, 2-Mild, 3-Moderate, and 4-Severe. | Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, and 28 | 
| Number of Subjects With Psoriasis Area and Severity Index (PASI) 50 | Number of subjects who achieved 50% or greater improvement from baseline PASI. The PASI scale is from 0 (no psoriasis) to 72 (complete erythroderma of the severest possible degree). | Baseline and Weeks 16 and 28 | 
| Number of Subjects With PASI 75 | Number of subjects who achieved 75% or greater improvement from baseline PASI. The PASI scale is from 0 (no psoriasis) to 72 (complete erythroderma of the severest possible degree). | Baseline and Weeks 16 and 28 | 
| Number of Subjects With PASI 90 | Number of subjects who achieved 90% or greater improvement from baseline PASI. The PASI scale is from 0 (no psoriasis) to 72 (complete erythroderma of the severest possible degree). | Baseline and Weeks 16 and 28 | 
| Number of Subjects With PASI 100 | Number of subjects who achieved 100% improvement from baseline PASI. The PASI scale is from 0 (no psoriasis) to 72 (complete erythroderma of the severest possible degree). | Baseline and Weeks 16 and 28 | 
| Mean Change From Baseline in Dermatology Life Quality Index (DLQI) | The DLQI consists of 10 questions and is scored from 0 (total lack of impairment) to 30 (life is very much impaired). A decrease in DLQI indicates improvement. | Baseline and Weeks 2, 8, 16, and 28 | 
| Number of Subjects Achieving a DLQI of 0 | Number of subjects achieving a DLQI score of 0, indicating total lack of impairment. The DLQI consists of 10 questions and is scored from 0 to 30 (life is very much impaired). A decrease in DLQI indicates improvement. | Baseline and Weeks 2, 8, 16, and 28 | 
| Mean Change From Baseline in Visual Analog Scale (VAS) for Psoriasis and Psoriatic Arthritis Pain | On one single VAS, subjects assessed their pain due to psoriasis (and psoriatic arthritis, if applicable). Mean change in psoriasis and psoriatic arthritis pain from Baseline as measured by a VAS from 0 (no pain) to 100 (pain as bad as it could be). | Baseline and Weeks 16 and 28 | 
| Mean Change From Baseline in Work Productivity and Activity Impairment Questionnaire: Psoriasis (WPAI:PSO) | WPAI:PSO assesses the effect on the subject's ability to work and perform regular activities in 4 areas: % work time (in hours) missed due to psoriasis, % impairment while working (on a scale from 0 [psoriasis having no effect] to 10 [psoriasis completely prevented subject from working]), % overall work impairment (on a scale from 0 [psoriasis having no effect] to 10 [psoriasis completely prevented subject from working]), and % activity impairment (on a scale from 0 [psoriasis having no effect on daily activities] to 10 [psoriasis completely prevented subject from doing daily activities]). | Baseline and Weeks 8, 16, and 28 | 
| Mean Change From Baseline in Patient Health Questionnaire (PHQ-9) | The PHQ-9 consists of 9 questions that assess how often over the past 2 weeks subjects had signs or symptoms of depression (0=not at all, 1=several days, 2=more than half days, and 3=nearly every day). The PHQ-9 is the sum of the scores from the 9 questions for a total range from 0 (not depressed at all) to 27 (depressed nearly every day). | Baseline and Weeks 2, 8, 16, and 28 | 
| Number of Subjects With Difficulties According to PHQ-9 | Based on the 9 questions of the PHQ-9, if subjects indicated any problems (PHQ-9 score > 0), the difficulty to do work, take care of things at home, and get along with people (question 10 of the PHQ) were assessed (not difficult at all, somewhat difficult, very difficult, and extremely difficult). | Baseline and Weeks 2, 8, 16, and 28 |