Comparison of CHS-0214 to Enbrel (Etanercept) in Patients With Rheumatoid Arthritis (RA)

Study Overview
=================
Brief Summary
-----------------
This is a two part study comparing CHS-0214 to Enbrel in patients with active rheumatoid arthritis and an inadequate response with Methotrexate (MTX) who are naive to biologic therapies. Pt.1 is a 24-week randomized, double-blind, active-control, parallel-group, multi-center global study. The primary end point is 20% improvement in American College of Rheumatology criteria (ACR-20) at week 24. Comparing CHS-0214 to Enbrel for efficacy and safety. Pt. 2 is an open-label single arm study in which patients with at least an ACR-20 response receive CHS-0214. Continued response and safety will be evaluated.

Official Title
-----------------
A Double-Blind, Randomized, Parallel-Group, Active-Control Study to Compare the Efficacy and Safety of CHS-0214 Versus Enbrel in Subjects With Rheumatoid Arthritis and Inadequate Response to Treatment With Methotrexate

Conditions
-----------------
Rheumatoid Arthritis

Intervention / Treatment
-----------------
* Drug: Etanercept
* Drug: CHS-0214


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female adults RA (Rheumatoid Arthritis) diagnosis for 6 months On stable dose of MTX of 8mg to 25mg per week Active disease: greater than 6 tender joints, greater than 6 swollen joints, C-reactive protein (CRP) greater than or equal to 0.5mg/dL, and disease activity score (DAS) with 28 joints (DAS28-CRP(4)) greater than or equal to 3.2 Exclusion Criteria: Use of prednisone greater than 10mg/day Use of greater than one non-steroidal anti-inflammatory drug (NSAID) Use of biologic therapies for any cause Chemistry and hematology values outside protocol specified range Positive QuantiFERON-tuberculosis (TB) Gold Test Evidence of active lung disease on chest x-ray Major systemic infections Presence of significant comorbid conditions Known allergy to latex Women who are pregnant or nursing

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Enbrel (etanercept)<br>Enbrel 50mg weekly times 24 weeks. | Drug: Etanercept<br>* Head-to-head comparison<br>* Other names: European Enbrel;|
| Experimental: CHS-0214<br>CHS-0214 50mg weekly times 24 weeks. | Drug: CHS-0214<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ACR-20 - 20% Improvement According to American College of Rheumatology Criteria | The primary efficacy endpoint in Part 1 was the percentage of subjects who achieved ACR20 (20% improvement according to American College of Rheumatology criteria) at week 24 compared to baseline (last non-missing value prior to first dose). Subjects were considered an ACR20 responder if when compared to baseline (last non-missing value prior to first dose), they achieved a 20% decrease in SJC (Swollen joint count), 20% decrease in TJC (Tender joint count), and 20% improvement in 3 of the following 5 measures: high sensitivity C reactive protein(hs-CRP), Health Assessment Questionnaire Disability Index(HAQ-DI), subjects global assessment of pain(SPA, VAS), subject's global assessment of disease activity(SGA-VAS), physician's global assessment of disease activity(PGA-VAS) | 24-weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ACR20 - (20% Improvement According to American College of Rheumatology Criteria) at Weeks 4, 8, 12, and 18 | Subjects were considered an ACR20 responder if, when compared to baseline (last non-missing value prior to first dose), they achieved a 20% decrease in SJC, 20% decrease in TJC, and 20% improvement in 3 of the following 5 measures: High sensitivity C-reactive protein (hs-CRP); Health Assessment Questionnaire-Disability Index (HAQ-DI); Subject's global assessment of pain (ie, subject's pain assessment [SPA]-visual analog scale [VAS]); Subject's global assessment of disease activity (SGA-VAS); and Physician's global assessment of disease activity (PGA-VAS). In these calculations, the percent change from baseline to endpoint was used to determine ACR20. For percentage change calculations, results were rounded to 5 decimal places prior to comparing to the threshold of 20%.For SJCs and TJCs, the assessment of efficacy was based on mean change from baseline (last non-missing value prior to first dose evaluation). | Weeks 4, 8, 12 and 18 | 
| Summary of Change in Tender Joint Count (TJC) by Study Visit | The average percent improvement from baseline in individual ACR response criteria: TJC (Tender joint count) the 66/68 Joint Count evaluates 68 joints for tenderness and pain with movement. The temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal (MCP), proximal interphalangeal (PIP), distal interphalangeal (DIP), hip, knee, ankle, tarsus, metatarsophalangeal (MTP), and interphalangeal of the feet are included in this joint count. Hip joints can be evaluated for tenderness. | Weeks 4,8,12,18,24,28,36,48 | 
| Summary of Change in Swollen Joint Count (SJC) by Study Visit | The 66/68 Joint Count evaluates 66 joints for swelling. The temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal (MCP), proximal interphalangeal (PIP), distal interphalangeal (DIP), hip, knee, ankle, tarsus, metatarsophalangeal (MTP), and interphalangeal of the feet are included in this joint count. | Weeks 4,8,12,18,24,28,36,48 | 
| Summary of Change in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Study Visit | HAQ-DI - Scales for each question range from 0-3 (0=without any difficulty; 1=with some difficulty; 2=with much difficulty; 3=Unable to do). The total for each category is determined by the highest score (greatest difficulty) for that category. The score for the disability index is the mean of the eight category scores. If more than 2 of the categories or 25% are missing, the scale won't be scored. If fewer than 2 or the categories are missing, the sum of the categories was divided by the number of answered categories. | Weeks 4,8,12,18,24,28,36,48 | 
| Summary of Change in Subject's Pain Assessment - Visual Analog Scale (SPA-VAS) by Study Visit | The score range for the SPA-VAS is 0-100 millimeters. One total score was reported for each assessment, no subscales exist. A lower score on the left side represents a better outcome (less pain) and the higher score is on the right side representing a worse outcome (more pain). | Weeks 4,8,12,18,24,28,36,48 | 
| Summary of Change in Physician's Global Assessment- Visual Assessment Scale (PGA-VAS) by Study Visit | The score range for PGA-VAS is 0-100 millimeters. The patient's assessment of disease activity - with the lowest score on the left side representing none to the highest score on the right side representing extremely active. | Weeks 4,8,12,18,24,28,36,48 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CHS-0214, Enbrel, RA, Biosimilar, Etanercept