Study to Demonstrate Equivalent Efficacy and to Compare Safety of Biosimilar Etanercept (GP2015) and Enbrel

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate equivalent efficacy of GP2015 and Enbrel® in patients with moderate to severe chronic plaque-type psoriasis with respect to PASI 75 response rate at Week 12.

Detailed Description
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The purpose of this confirmatory safety and efficacy study (GP15-302) was to demonstrate equivalence in efficacy and similarity in safety and immunogenicity of GP2015 and Enbrel (EU-authorized) in patients with moderate to severe chronic plaque-type psoriasis and to evaluate the effects of repeated switching between GP2015 and Enbrel on efficacy, overall safety, and immunogenicity. Since only EU-authorized Enbrel was utilized in this study, the use of the term Enbrel throughout this report describes EU-authorized Enbrel only.

Official Title
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A Randomized, Double-blind, Multicenter Study to Demonstrate Equivalent Efficacy and to Compare Safety and Immunogenicity of a Biosimilar Etanercept (GP2015) and Enbrel® in Patients With Moderate to Severe Chronic Plaque-type Psoriasis

Conditions
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Chronic Stable Plaque Psoriasis

Intervention / Treatment
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* Drug: GP2015 Etanercept
* Drug: Enbrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women at least 18 years of age at time of screening Chronic plaque-type psoriasis diagnosed for at least 6 months before baseline Moderate to severe psoriasis as defined at baseline by: PASI score of 10 or greater and, Investigator´s Global Assessment score of 3 or greater (based on a scale of 0 - 4) and, Body Surface Area affected by plaque-type psoriasis of 10% or greater Chronic plaque-type psoriasis patients who have previously received phototherapy or systemic psoriasis therapy at least once or who are candidates for such therapies in the opinion of the investigator. Exclusion Criteria: Forms of psoriasis other than chronic plaque-type Drug-induced psoriasis Ongoing use of prohibited treatments Previous exposure to etanercept Active ongoing inflammatory diseases other than psoriasis that might confound the evaluation of the benefit of treatment with etanercept Other In-/Exclusion criteria may apply

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GP2015 Etanercept<br>Solution for subcutaneous injection in pre-filled syringe. The drug is administered in a dose of 50 mg twice weekly for the first 12 weeks and 50 mg once weekly thereafter | Drug: GP2015 Etanercept<br>* Sandoz has developed GP2015 Etanercept (Sandoz's code for the drug product containing the active ingredient etanercept) to be biosimilar to Enbrel.<br>* Other names: Etanercept;|
| Active Comparator: Enbrel ® Etanercept<br>Solution for subcutaneous injection in pre-filled syringe. The drug is administered in a dose of 50 mg twice weekly for the first 12 weeks and 50 mg once weekly thereafter | Drug: Enbrel<br>* Enbrel is used as reference product to GP2015.<br>* Other names: Etanercept;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PASI 75 Response Rate at Week 12 - GP2015 Etanercept vs. Enbrel ® Etanercept | The 95% CI for the Psoriasis Area and Severity Index (PASI) 75 response rate differences at Week12 between GP2015 Etanercept and Enbrel ® Etanercept. PASI 75 response: patients who achieved ≥ 75% improvement (reduction) in PASI score compared to baseline were defined as PASI 75 responders. PASI scores can range from 0, corresponding to no signs of psoriasis up to theoretic maximum of 72.0, which means a higher PASI score reflects a higher psoriasis activity. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in PASI Score up to Week 12 | The key secondary efficacy endpoint was the % change from baseline in PASI score up to Week 12. PASI scores can range from 0, corresponding to no signs of psoriasis up to theoretic maximum of 72.0, which means a higher PASI score reflects a higher psoriasis activity. Two approaches (longitudinal approach applying a Mixed Model Repeated Measures and Averaged Treatment Effect approach applying an ANCOVA model) were employed in order to calculate 2-sided 95% confidence intervals (CI) for the difference between the treatment groups. | 12 weeks | 
| PASI 50, 75 and 90 Response Rates | Percentage of patients achieving Psoriasis Area and Severity Index (PASI) 50, PASI 75, and PASI 90 responses at Week 12. PASI 50 response: patients who achieved ≥ 50% improvement (reduction) in PASI score compared to baseline were defined as PASI 50 responders .PASI 90 response: patients who achieved ≥ 90% improvement (reduction) in PASI score compared to baseline were defined as PASI 90 responders . | Week12 | 
| Injection Site Reactions | Percentage of patients with injection site reactions up to Week 52 | Week52 | 
| Immunogenicity: Measurement of Rate of ADA Formations Against GP2015 Etanercept and Enbrel ® Etanercept | Immunogenicity was analyzed by the percentage of patients with positive anti-drug antibodies (ADA) to either GP2015 Etanercept or Enbrel ® up to Week 52. | Week 52 |