Comparison of CHS-0214 to Enbrel (Etanercept) in Patients With Rheumatoid Arthritis (RA) (CHS-0214-02)

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

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Etanercept; Drug: CHS-0214

• Study Type: Interventional
• Enrollment (Actual): 647
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belarus
  • Brest, Belarus, 224027
    • Brest Regional Clinical Hospital
  • Gomel, Belarus, 246029
    • Gomel Regional Clinical Hospital
  • Grodno, Belarus, 230017
    • Grodno Regional Clinical Hospital
  • Minsk, Belarus, 220013
    • City Clinical Hospital #1 - Belarus
  • Minsk, Belarus, 220116
    • City Clinical Hospital #9 - Belarus
  • Vitebsk, Belarus, 210037
    • Vitebsk Regional Clinical Hospital
• France
  • Grenoble, France, 38434
    • Hôpital Michallon - CHU de Grenobl
  • Le Kremlin-Bicetre, France, 94275
    • CHU Bicêtre
  • Orleans Cedex, France, 45067
    • Centre Hospitalier Regional D'Orleans
  • Paris, France, 75014
    • Hopital Cochin-Saint Vincent de Paul
  • Saint-Etienne, France, 42055
    • Hopital de Saint Etienne
• Germany
  • Bad Abbach, Germany, 93077
    • Asklepios Klinikum Bad Abbach
  • Dresden, Germany, 01069
    • Klinische Forschung Dresden GmbH
  • Frankfurt, Germany, 60528
    • Center of Innovative Diagnostics and Therapeutics Rheumatology/Immunology
  • Gottingen, Germany, 37075
    • Universitatsmedizin Gottingen
  • Magdeburg, Germany, 39112
    • SMO.MD GmbH - Zentrum fuer klinische Studien
• Hungary
  • Baja, Hungary, 6500
    • St. Rokus Hospital, BAJA
  • Balatonfured, Hungary, 8230
    • DRC Gyogzszervizsgalo Kozpont
  • Budapest, Hungary, 1023
    • Orszagos Reumatologiai es Fizioterapias Intezet
  • Budapest, Hungary, 1036
    • Qualiclinic Kft
  • Gyula, Hungary, 5700
    • Bekes Megyei Pandy Kalman Korhaz
  • Szeged, Hungary, 6725
    • University of Szeged, Faculty of Medicine
  • Szikszo, Hungary, 3800
    • Rakoczi Ferenc Korhaz-CRU Hungary (KFT)
• Israel
  • Haifa, Israel, 3109601
    • Rambam Medical Center
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center
  • Tel Hashomer, Israel, 52621
    • Sheba Medical Center
  • Zerifin, Israel, 70300
    • Assaf Harofeh Medical Center
• Japan
  • Aichi, Japan, 453-8511
    • Japanese Red Cross Nagoya Daiichi Hospital
  • Ehime, Japan, 790-0905
    • Yamada Rheumatology Clinic
  • Fukuoka, Japan, 810-0001
    • Kondo clinic for rheumatism and orthopaedics
  • Fukuoka, Japan, 807-8556
    • University of Occupational and Environmental Health Hospital
  • Fukuoka, Japan, 812-0025
    • Medical Co. LTA PS Clinic
  • Fukuoka, Japan, 830-8543
    • St Mary;s Hospital
  • Fukuoka-shi, Japan, 814-002
    • SHONO Rheumatism Clinic
  • Hiroshima, Japan, 730-0017
    • Hiroshima Rheumatology Clinic
  • Hyogo, Japan, 673-1462
    • Matsubara Mayflower Hospital
  • Hyogo, Japan, 650-0044
    • Medical Corporation Nakayama Clinic
  • Iwate, Japan, 020-0015
    • Yoshida orthopaedic and rheumatology Clinic
  • Kagoshima, Japan, 890-0055
    • Eiraku Clinic
  • Kagoshima, Japan, 890-0067
    • Izumihara Rheumatic and Medical Clinic
  • Kanagawa, Japan, 212-0014
    • Kawasaki Rheumatism and Internal Medicine Clinic
  • Kumamoto, Japan, 862-0976
    • Kumamoto Orthopaedic Hospital
  • Miyagi, Japan, 980-6166
    • Munakata Yasuhiko Clinic
  • Miyagi, Japan, 981-0112
    • Yu-Family Clinic
  • Miyagi, Japan, 982-0032
    • Sendai Taihaku Hospital
  • Miyazaki, Japan, 880-0053
    • Kai Clinic
  • Miyazaki, Japan, 880-0122
    • Zenjinkai Shimin no Mori Hospital
  • Morioka Iwate, Japan, 020-0034
    • Komagamine Orthopaedic Rheumatic Clinic
  • Nagasaki, Japan, 852-8501
    • Nagasaki University Hospital
  • Nagasaki, Japan, 850-0832
    • Nagasaki Medical Hospital of Rheumatology
  • Nagasaki, Japan, 857-1195
    • Sasebo Chuo Hospital
  • Oita, Japan, 870-0823
    • Oribe Clinic of Rheumatism and Medicine
  • Oita, Japan, 870-1155
    • Otsuka Clinica of Rheumatism and Medicine
  • Osaka, Japan, 598-0048
    • Rinku Hashimoto Rheumatology Orthopedics
  • Saitama, Japan, 343-8577
    • Koshigaya Municipal Hospital
  • Saitama, Japan, 359-1111
    • Medical Corporation Kojyokai Hirose Clinic
  • Sapporo, Japan, 063-0811
    • Hokkaido Medical Center for Rheumatic Diseases
  • Tokyo, Japan, 160-8582
    • Keio University Hospital
  • Tokyo, Japan, 104-8560
    • St. Luke's International Hospital
  • Yamaguchi, Japan, 745-0824
    • Miyasato Clinic
  • Yamaguchi, Japan, 752-0976
    • Tokito Clinic Rheumatology and Orthopaedics, Surgery
  • Aichi
    • Nagoya-shi, Aichi, Japan, 466-8560
      • Nagoya University Hospital
  • Gunma
    • Takasaki-shi, Gunma, Japan, 370-0053
      • Inoue Hospital
  • Hiroshimashi
    • Nishi-ku, Hiroshimashi, Japan, 733-0032
      • Hiroshima Clinic
  • Miyagi
    • Sendai-City, Miyagi, Japan, 981-3135
      • Izumi Himawari Clinica
  • Nagasaki
    • Omura-shi, Nagasaki, Japan, 856-0836
      • Miyashita Rheumatology Clinic
  • Okayama
    • Okayama-Shi, Okayama, Japan, 700-8607
      • Japanese Red Cross Okayama Hospital
• Poland
  • Elblag, Poland, 82-300
    • Centrum Kliniczno Badawcze
  • Gdynia, Poland, 81-384
    • Synexus Polska Sp. z o.o. Oddzial w Gdyni
  • Grodzisk Mazowiecki, Poland, 05825
    • Mazowieckie Centrum Badan Klinicznych (MCBK) SC
  • Katowice, Poland, 40-040
    • Synexus Polska Sp. z o.o. Oddzial w Katowicach
  • Kodz, Poland, 90242
    • Centrum Terapii Wspólczesne
  • Nadarzyn, Poland, 05-830
    • NZOZ Lecznica MAK-MED
  • Olsztyn, Poland, 10696
    • Profmedicus sp. z o.o
  • Poznan, Poland, 60702
    • Centrum Medyczne SYNEXUS POZNAN
  • Poznan, Poland, 61-639
    • Prywatna Praktyka Lekarska Prof UM dr hab. Med. Pawel Hrycaj
  • Warszawa, Poland, 01-192
    • Synexus Polska Sp. z o.o. Oddzial w Warszawie
  • Warszawa, Poland, 01518
    • Centrum Medyczne AMED
  • Wroclaw, Poland, 53-224
    • Biogenes NZOZ
  • Wroclaw, Poland, 53-413
    • Synexus Polska sp. z o.o
• Russian Federation
  • Ekaterinburg, Russian Federation, 620102
    • Sverdlovsk Regional Clinical Hospital #1
  • Krasnoyarsk, Russian Federation, 660022
    • Krasnoyarsk Medical Academy
  • Moscow, Russian Federation, 111539
    • State Healthcare Institution of Moscow City Clinical Hospital #15 n.a. O.M. Filatov
  • Moscow, Russian Federation, 115404
    • Practicheskaya Meditsina, Ltd
  • Petrozavodsk, Russian Federation, 185019
    • Republican Hospital n.a. V.A. Baranov
  • Smolensk, Russian Federation, 214019
    • Smolensk State Medical University (SSMU)
  • St Petersburg, Russian Federation, 198260
    • St. Petersburg State Healthcare Institution "Consultative diagnostic center #85
  • St. Petersburg, Russian Federation, 196084
    • Medical Research Institute, LLC
  • Yaroslavl, Russian Federation, 150003
    • Municipal Healthcare Institution "Emergency Clinical Hospital n.a. N.V. Soloviev
  • Yekaterinburg, Russian Federation, 620149
    • MBI "Central City Clinical Hospital #6
• South Africa
  • Cape Town, South Africa, 7500
    • Dr CI Louw
  • Durban, South Africa, 4001
    • Dr S Nayiager
  • Johannesburg, South Africa, 2193
    • Wits Donald Gordon Clinical Trial Site
  • Mpumalanga, South Africa, 2330
    • Drs Dindar and Partners
  • Pinelands, South Africa, 7405
    • Private Practice - Cathy Spargo
  • Pretoria, South Africa, 0084
    • Emmed Research
  • Pretoria, South Africa, 0002
    • Jakaranda Hospital Pretoria
  • Stellenbosch, South Africa, 7600
    • Winelands Rheumatology Centre
• Spain
  • Madrid, Spain, 28034
    • Hospital Universitario Ramón y Cajal
  • Madrid, Spain, 28046
    • Hospital La Paz
  • Malaga, Spain, 29009
    • Hospital Regional Universitario de Málaga
• United Kingdom
  • Brighton, United Kingdom, BN25PE
    • Royal Sussex County Hospital
  • Harrogate, United Kingdom, HG27SX
    • Harrogate District NHS Foundation Trust
  • Merseyside, United Kingdom, CH495PE
    • Wirral University Teaching Hospital NHS Foundation Trust
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Elite Clinical Studies
    • Phoenix, Arizona, United States, 85020
      • Arizona Research Center
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • NEA Baptist Clinic
  • California
    • Anaheim, California, United States, 92801
      • Dream Team Clinical Research
    • Lakewood, California, United States, 90712
      • Advanced Medical Research
    • Long Beach, California, United States, 90808
      • Pro Health Partners
    • Orange, California, United States, 92868
      • St. Joseph Hospital of Orange
    • Palm Desert, California, United States, 92260
      • Desert Medical Advances
    • Richmond, California, United States, 94801
      • Kaiser Permanente - CA
    • Roseville, California, United States, 95661
      • Med Investigators, Inc
    • Santa Monica, California, United States, 90404
      • Troum Medical Associates
    • Upland, California, United States, 91786
      • Inland Rheumatology Clinical Trials INC
  • Colorado
    • Centennial, Colorado, United States, 80112
      • IMMUNOe International Research Centers
  • Florida
    • Kissimmee, Florida, United States, 34741
      • Hope Clinical Research
    • Orlando, Florida, United States, 32804
      • Advanced Medical Research, Inc
    • Saint Petersburg, Florida, United States, 33708
      • Allergy & Rheumatology Associates LLC
    • Tampa, Florida, United States, 33614
      • HealthPoint Medical Group
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Bluegrass Community Research, Inc
  • Maryland
    • Wheaton, Maryland, United States, 20902
      • The Center for Rheumatology and Bone Research
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • Clinical Pharmacology Study Group
  • Missouri
    • Saint Louis, Missouri, United States, 63128
      • St. Louis Center for Clinical Research
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Arthritis Center of Nebraska
    • Omaha, Nebraska, United States, 68198
      • Pacific Arthritis Center Medical Group
    • Omaha, Nebraska, United States, 68198
      • Rheumatoid Arthritis Investigational Network
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • Great Neck, New York, United States, 11021
      • North Shore University Hospital
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • DJL Clinical Research
    • Wilmington, North Carolina, United States, 28401
      • Pmg Research Of Wilmington Llc
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center For Clinical Research
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Low Country Rheumatology
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • Arthritis Clinic
  • Texas
    • Arlington, Texas, United States, 76015
      • Texas Physicians Medical Research Group
    • Dallas, Texas, United States, 75231
      • Metroplex Clinical Research Center
    • Houston, Texas, United States, 77036
      • Pioneer Research Solutions Inc
  • Washington
    • Spokane, Washington, United States, 99204
      • Arthritis Northwest Rheumatology PLLC
  • Wisconsin
    • Glendale, Wisconsin, United States, 53217
      • Rheumatic Disease Center
    • Onalaska, Wisconsin, United States, 54650
      • Gundersen Lutheran Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Coherus Biosciences, Inc.
• Collaborators: Daiichi Sankyo Co., Ltd.
• Investigators: Study Director: Barbara K Finck, M.D., Coherus Biosciences, Inc.

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: April 14, 2014
• First Submitted That Met QC Criteria: April 15, 2014
• First Posted (Estimate): April 16, 2014

Study Record Updates

• Last Update Posted (Actual): June 26, 2019
• Last Update Submitted That Met QC Criteria: June 7, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Enbrel; Biosimilar; RA; Etanercept; CHS-0214
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Etanercept
• Other Study ID Numbers: CHS-0214-02