Study to Evaluate the Efficacy of Etanercept Treatment in Adults Who Failed Therapy With Apremilast

Study Overview
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Brief Summary
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To evaluate the efficacy of etanercept in adults with moderate to severe plaque psoriasis who have failed therapy with apremilast (Otezla).

Detailed Description
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This is a multicenter, open-label, single-arm, phase 4, estimation study in adults with plaque psoriasis (PsO) who have failed apremilast. The study will consist of a screening period of up to 45 days, a 24-week treatment period with study visits every 4 weeks, and a 30-day follow-up period for safety. Etanercept dosing will follow the recommended label dosing for adults with plaque psoriasis.

Official Title
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Open Label Study to Evaluate the Efficacy of Etanercept Treatment in Subjects With Moderate to Severe Plaque Psoriasis Who Have Failed Therapy With Apremilast

Conditions
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Plaque Psoriasis

Intervention / Treatment
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* Drug: Etanercept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has provided informed consent prior to initiation of any study specific activities/procedures Male or female subject is ≥ 18 years of age at time of screening Subject is a candidate for systemic therapy or phototherapy in the opinion of the investigator Subject has moderate to severe plaque psoriasis (PsO) with involved body surface area (BSA) ≥ 10%, psoriasis area and severity index (PASI) ≥ 10 and static physician's global assessment (sPGA) ≥ 3 at screening and baseline Subject is currently receiving treatment with apremilast for moderate to severe plaque PsO or subject has discontinued treatment with apremilast for PsO within the past 3 months prior to screening Subject has failed therapy with apremilast for moderate to severe plaque PsO defined as either (1) failure to achieve adequate clinical response in the opinion of the investigator, (2) loss of adequate clinical response in the opinion of the investigator or (3) intolerability to apremilast in the opinion of the investigator Subject has received at least 4 weeks of apremilast treatment for moderate to severe plaque PsO (this only applies for subjects who are qualifying by failure to achieve adequate clinical response or loss of adequate clinical response, this does not apply for subjects who are qualifying by intolerability to apremilast) Subject has not had significant known weight increase or decrease (≥ 10%) during apremilast treatment Subject is < 264 lbs at screening and baseline -Subject has a negative test for hepatitis B surface antigen, hepatitis B core antibody and hepatitis C antibody Subject has no known history of tuberculosis. Exclusion Criteria: Skin disease related -Subject has active erythrodermic, pustular, guttate psoriasis, or medication induced psoriasis, or other skin conditions at the time of the screening visit (for example, eczema) that would interfere with evaluations of the effect of investigational product on PsO. Other Medical Conditions Subject has one or more significant concurrent medical conditions per investigator judgment, including the following Poorly controlled diabetes Chronic kidney disease stage IIIb, IV, or V Symptomatic heart failure (New York Heart Association class II, III, or IV) Myocardial infarction or unstable angina pectoris within the past 12 months prior to randomization Uncontrolled hypertension Severe chronic pulmonary disease (eg, requiring oxygen therapy) Multiple sclerosis or any other demyelinating disease Liver disease Anemia Major chronic inflammatory disease or connective tissue disease other than psoriasis and/or psoriatic arthritis (for example, systemic lupus erythematosus with the exception of secondary Sjogren's syndrome) Subject has active malignancy, including evidence of cutaneous basal or squamous cell carcinoma or melanoma, Merkel cell carcinoma or history of cancer (other than fully resected and surgically cured cutaneous basal cell and squamous cell carcinoma) within 5 years before the first dose of investigational product.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Etanercept<br>Participants received etanercept 50 mg subcutaneously twice weekly for 12 weeks followed by 50 mg once weekly for an additional 12 weeks. | Drug: Etanercept<br>* Administered subcutaneously twice weekly for 12 weeks then once weekly for an additional 12 weeks.<br>* Other names: Enbrel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a PASI 75 Response at Week 12 | A PASI 75 response is a 75% or greater improvement (reduction) from baseline in PASI score. The PASI measures the average redness (erythema), thickness (induration), and scaliness (each graded on a 0 to 4 scale) of psoriasis lesions, weighted by the area of involvement in the four main body areas (i.e., head and neck, trunk, upper extremities, and lower extremities). PASI scores can range from 0 to 72, with higher scores indicating greater severity and/or more extensive psoriasis. | Baseline and week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a PASI 75 Response at Each Visit | A PASI 75 response is a 75% or greater improvement (reduction) from baseline in PASI score. The PASI measures the average redness (erythema), thickness (induration), and scaliness (each graded on a 0 to 4 scale) of psoriasis lesions, weighted by the area of involvement in the four main body areas (i.e., head and neck, trunk, upper extremities, and lower extremities). PASI scores can range from 0 to 72, with higher scores indicating greater severity and/or more extensive psoriasis. | Baseline and weeks 4, 8, 12, 16, 20, and 24 | 
| Percentage of Participants With a PASI 50 Response at Each Visit | A PASI 50 response is a 50% or greater improvement (reduction) from baseline in PASI score. The PASI measures the average redness (erythema), thickness (induration), and scaliness (each graded on a 0 to 4 scale) of psoriasis lesions, weighted by the area of involvement in the four main body areas (i.e., head and neck, trunk, upper extremities, and lower extremities). PASI scores can range from 0 to 72, with higher scores indicating greater severity and/or more extensive psoriasis. | Baseline and weeks 4, 8, 12, 16, 20, and 24 | 
| Percentage of Participants With a PASI 90 Response at Each Visit | A PASI 90 response is a 90% or greater improvement (reduction) from baseline in PASI score. The PASI measures the average redness (erythema), thickness (induration), and scaliness (each graded on a 0 to 4 scale) of psoriasis lesions, weighted by the area of involvement in the four main body areas (i.e., head and neck, trunk, upper extremities, and lower extremities). PASI scores can range from 0 to 72, with higher scores indicating greater severity and/or more extensive psoriasis. | Baseline and weeks 4, 8, 12, 16, 20, and 24 | 
| Percent Change From Baseline in Psoriasis Area and Severity Index (PASI) | The PASI measures the average redness (erythema), thickness (induration), and scaliness (each graded on a 0 to 4 scale) of psoriasis lesions, weighted by the area of involvement in the four main body areas (i.e., head and neck, trunk, upper extremities, and lower extremities). PASI scores can range from 0 to 72, with higher scores indicating greater severity and/or more extensive psoriasis. Percent change from baseline was calculated as (Baseline Value - Post-baseline Value) / Baseline Value * 100, hence a positive value indicates improvement. | Baseline and weeks 4, 8, 12, 16, 20, and 24 | 
| Percentage of Participants With an sPGA Score of 0 (Clear) or 1 (Almost Clear) at Each Visit | The sPGA is a 6-point scale ranging from 0 (clear) to 5 (very severe) used to measure the severity of disease (induration, scaling, and erythema). A sPGA response is defined as a sPGA value of clear (score 0) or almost clear (score 1). | Weeks 4, 8, 12, 16, 20, and 24 | 
| Percentage of Participants With an sPGA Score of 0, 1 or 2 at Each Visit | The sPGA is a 6-point scale ranging from 0 (clear) to 5 (very severe) used to measure the severity of disease (induration, scaling, and erythema). The percentage of participants with a score of 0 (clear), 1 (almost clear) or 2 (mild) is reported. | Weeks 4, 8, 12, 16, 20, and 24 | 
| Static Physician Global Assessment (sPGA) at Each Visit | The sPGA is a 6-point scale ranging from 0 (clear) to 5 (very severe) used to measure the severity of disease (induration, scaling, and erythema). | Weeks 4, 8, 12, 16, 20, and 24 | 
| Percentage of Participants With at Least a 1 Grade Improvement in sPGA From Baseline | The sPGA is a 6-point scale ranging from 0 (clear) to 5 (very severe) used to measure the severity of disease (induration, scaling, and erythema). The percentage of participants with an improvement from baseline of ≥ 1 grade is reported. | Baseline and weeks 4, 8, 12, 16, 20, and 24 | 
| Percentage of Participants With at Least a 2 Grade Improvement in sPGA From Baseline | The sPGA is a 6-point scale ranging from 0 (clear) to 5 (very severe) used to measure the severity of disease (induration, scaling, and erythema). The percentage of participants with an improvement from baseline of ≥ 2 grades is reported. | Baseline and weeks 4, 8, 12, 16, 20, and 24 | 
| Percent Change From Baseline in the Percentage of Body Surface Area (BSA) Involved With Psoriasis at Each Visit | A measurement of psoriasis involvement, given as the physician's assessment of the percentage of the participant's total body surface area (BSA) involved with psoriasis. The percent of BSA affected was estimated by assuming that the participant's palm, excluding the fingers and thumb, represented roughly 1% of the body's surface. Percent change from baseline was calculated as (Baseline Value - Post-baseline Value) / Baseline Value * 100, hence a positive value indicates improvement. | Baseline and weeks 4, 8, 12, 16, 20, and 24 | 
| Psoriasis Symptom Inventory (PSI) Total Score at Each Visit | Participants rated the severity of their psoriasis signs and symptoms on an 8-item questionnaire (itch, redness, scaling, burning, stinging, cracking, flaking, pain) based on the past 7 days. Each item was scored on a 5-point scale from 0 (not at all severe) to 4 (very severe). The total score is the sum of the 8 responses, and ranges from 0 to 32. Higher scores indicate more severe psoriasis. | Weeks 1, 2, 3, 4, 8, 12, 16, 20, and 24 | 
| PSI Itch From Psoriasis Component Score at Each Visit | Participants rated the severity of their psoriasis signs and symptoms on an 8-item questionnaire (itch, redness, scaling, burning, stinging, cracking, flaking, pain) based on the past 7 days. Each item was scored on a 5-point scale from 0 (not at all severe) to 4 (very severe). | Weeks 1, 2, 3, 4, 8, 12, 16, 20, and 24 | 
| PSI Redness of Skin Lesions Component Score at Each Visit | Participants rated the severity of their psoriasis signs and symptoms on an 8-item questionnaire (itch, redness, scaling, burning, stinging, cracking, flaking, pain) based on the past 7 days. Each item was scored on a 5-point scale from 0 (not at all severe) to 4 (very severe). | Weeks 1, 2, 3, 4, 8, 12, 16, 20, and 24 | 
| PSI Scaling of Skin Lesions Component Score at Each Visit | Participants rated the severity of their psoriasis signs and symptoms on an 8-item questionnaire (itch, redness, scaling, burning, stinging, cracking, flaking, pain) based on the past 7 days. Each item was scored on a 5-point scale from 0 (not at all severe) to 4 (very severe). | Weeks 1, 2, 3, 4, 8, 12, 16, 20, and 24 | 
| PSI Burning of Skin Lesions Component Score at Each Visit | Participants rated the severity of their psoriasis signs and symptoms on an 8-item questionnaire (itch, redness, scaling, burning, stinging, cracking, flaking, pain) based on the past 7 days. Each item was scored on a 5-point scale from 0 (not at all severe) to 4 (very severe). | Weeks 1, 2, 3, 4, 8, 12, 16, 20, and 24 | 
| PSI Stinging of Skin Lesions Component Score at Each Visit | Participants rated the severity of their psoriasis signs and symptoms on an 8-item questionnaire (itch, redness, scaling, burning, stinging, cracking, flaking, pain) based on the past 7 days. Each item was scored on a 5-point scale from 0 (not at all severe) to 4 (very severe). | Weeks 1, 2, 3, 4, 8, 12, 16, 20, and 24 | 
| PSI Cracking of Skin Lesions Component Score at Each Visit | Participants rated the severity of their psoriasis signs and symptoms on an 8-item questionnaire (itch, redness, scaling, burning, stinging, cracking, flaking, pain) based on the past 7 days. Each item was scored on a 5-point scale from 0 (not at all severe) to 4 (very severe). | Weeks 1, 2, 3, 4, 8, 12, 16, 20, and 24 | 
| PSI Flaking of Skin Lesions Component Score at Each Visit | Participants rated the severity of their psoriasis signs and symptoms on an 8-item questionnaire (itch, redness, scaling, burning, stinging, cracking, flaking, pain) based on the past 7 days. Each item was scored on a 5-point scale from 0 (not at all severe) to 4 (very severe). | Weeks 1, 2, 3, 4, 8, 12, 16, 20, and 24 | 
| PSI Pain From Skin Lesions Component Score at Each Visit | Participants rated the severity of their psoriasis signs and symptoms on an 8-item questionnaire (itch, redness, scaling, burning, stinging, cracking, flaking, pain) based on the past 7 days. Each item was scored on a 5-point scale from 0 (not at all severe) to 4 (very severe). | Weeks 1, 2, 3, 4, 8, 12, 16, 20, and 24 | 
| Patient Assessment of Treatment Satisfaction at Week 12 | Participants indicated their level of satisfaction with the medication's control of psoriasis on a scale from very dissatisfied to very satisfied. | Week 12 | 
| Patient Assessment of Treatment Satisfaction at Week 24 | Participants indicated their level of satisfaction with the medication's control of psoriasis on a scale from very dissatisfied to very satisfied. | Week 24 | 
| Percent Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at Weeks 12 and 24 | The dermatology life quality index (DLQI) is a skin disease-specific instrument to evaluate health-related quality of life. The DLQI questionnaire asks participants to evaluate the degree that psoriasis has affected their quality of life in the last week, and includes the following parameters: symptoms and feelings, daily activities, leisure activities, work or school activities, personal relationships and treatment related feelings. Participants answered 10 questions on a scale from 0 (not at all) to 3 (very much); the range of the total score is from 0 (best possible score) to 30 (worst possible score). Percent change from baseline was calculated as (Baseline Value - Post-baseline Value) / Baseline Value * 100, hence a positive value indicates improvement. | Baseline and weeks 12 and 24 | 
| Number of Participants With Adverse Events |  | From first dose of etanercept to 30 days after last dose, up to 28 weeks. |