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

Rheumatoid Arthritis Clinical Trial

— CHS-0214-02  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02115750
• Other study ID #: CHS-0214-02
• Status: Completed
• Phase: Phase 3
• Start date: May 2014
• Est. completion date: May 2016

Study information

• Verified date: June 2019
• Source: Coherus Biosciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 647
• Est. completion date: May 2016
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Etanercept
Head-to-head comparison
• CHS-0214

Locations

Country	Name	City	State
Belarus	Brest Regional Clinical Hospital	Brest
Belarus	Gomel Regional Clinical Hospital	Gomel
Belarus	Grodno Regional Clinical Hospital	Grodno
Belarus	City Clinical Hospital #1 - Belarus	Minsk
Belarus	City Clinical Hospital #9 - Belarus	Minsk
Belarus	Vitebsk Regional Clinical Hospital	Vitebsk
France	Hôpital Michallon - CHU de Grenobl	Grenoble
France	CHU Bicetre	Le Kremlin-Bicetre
France	Centre Hospitalier Regional D'Orleans	Orleans Cedex
France	Hopital Cochin-Saint Vincent de Paul	Paris
France	Hopital de Saint Etienne	Saint-Etienne
Germany	Asklepios Klinikum Bad Abbach	Bad Abbach
Germany	Klinische Forschung Dresden GmbH	Dresden
Germany	Center of Innovative Diagnostics and Therapeutics Rheumatology/Immunology	Frankfurt
Germany	Universitätsmedizin Göttingen	Gottingen
Germany	SMO.MD GmbH - Zentrum fuer klinische Studien	Magdeburg
Hungary	St. Rokus Hospital, BAJA	Baja
Hungary	DRC Gyogzszervizsgalo Kozpont	Balatonfured
Hungary	Orszagos Reumatologiai es Fizioterapias Intezet	Budapest
Hungary	Qualiclinic Kft	Budapest
Hungary	Békés Megyei Pándy Kálmán Kórház	Gyula
Hungary	University of Szeged, Faculty of Medicine	Szeged
Hungary	Rakoczi Ferenc Korhaz-CRU Hungary (KFT)	Szikszo
Israel	Rambam Medical Center	Haifa
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Israel	Sheba Medical Center	Tel Hashomer
Israel	Assaf Harofeh Medical Center	Zerifin
Japan	Japanese Red Cross Nagoya Daiichi Hospital	Aichi
Japan	Yamada Rheumatology Clinic	Ehime
Japan	Kondo Clinic for Rheumatism and Orthopaedics	Fukuoka
Japan	Medical Co. LTA PS Clinic	Fukuoka
Japan	St Mary;s Hospital	Fukuoka
Japan	University of Occupational and Environmental Health Hospital	Fukuoka
Japan	Shono Rheumatism Clinic	Fukuoka-shi
Japan	Hiroshima Rheumatology Clinic	Hiroshima
Japan	Matsubara Mayflower Hospital	Hyogo
Japan	Medical Corporation Nakayama Clinic	Hyogo
Japan	Yoshida Orthopaedic and Rheumatology Clinic	Iwate
Japan	Eiraku Clinic	Kagoshima
Japan	Izumihara Rheumatic and Medical Clinic	Kagoshima
Japan	Kawasaki Rheumatism and Internal Medicine Clinic	Kanagawa
Japan	Kumamoto Orthopaedic Hospital	Kumamoto
Japan	Munakata Yasuhiko Clinic	Miyagi
Japan	Sendai Taihaku Hospital	Miyagi
Japan	Yu-Family Clinic	Miyagi
Japan	Kai Clinic	Miyazaki
Japan	Zenjinkai Shimin no Mori Hospital	Miyazaki
Japan	Komagamine Orthopaedic Rheumatic Clinic	Morioka Iwate
Japan	Nagasaki Medical Hospital of Rheumatology	Nagasaki
Japan	Nagasaki University Hospital	Nagasaki
Japan	SaSebo Chuo Hospital	Nagasaki
Japan	Nagoya University Hospital	Nagoya-shi	Aichi
Japan	Hiroshima Clinic	Nishi-ku	Hiroshimashi
Japan	Oribe Clinic of Rheumatism and Medicine	Oita
Japan	Otsuka Clinica of Rheumatism and Medicine	Oita
Japan	Japanese Red Cross Okayama Hospital	Okayama-Shi	Okayama
Japan	Miyashita Rheumatology Clinic	Omura-shi	Nagasaki
Japan	Rinku Hashimoto Rheumatology Orthopedics	Osaka
Japan	Koshigaya Municipal Hospital	Saitama
Japan	Medical Corporation Kojyokai Hirose Clinic	Saitama
Japan	Hokkaido Medical Center for Rheumatic Diseases	Sapporo
Japan	Izumi Himawari Clinica	Sendai-City	Miyagi
Japan	Inoue Hospital	Takasaki-shi	Gunma
Japan	Keio University Hospital	Tokyo
Japan	St. Luke's International Hospital	Tokyo
Japan	Miyasato Clinic	Yamaguchi
Japan	Tokito Clinic Rheumatology and Orthopaedics, Surgery	Yamaguchi
Poland	Centrum Kliniczno Badawcze	Elblag
Poland	Synexus Polska Sp. z o.o. Oddzial w Gdyni	Gdynia
Poland	Mazowieckie Centrum Badan Klinicznych (MCBK) SC	Grodzisk Mazowiecki
Poland	Synexus Polska Sp. z o.o. Oddzial w Katowicach	Katowice
Poland	Centrum Terapii Wspólczesne	Kodz
Poland	NZOZ Lecznica MAK-MED	Nadarzyn
Poland	Profmedicus sp. z o.o	Olsztyn
Poland	Centrum Medyczne SYNEXUS Poznan	Poznan
Poland	Prywatna Praktyka Lekarska Prof UM dr hab. Med. Pawel Hrycaj	Poznan
Poland	Centrum Medyczne AMED	Warszawa
Poland	Synexus Polska Sp. z o.o. Oddzial w Warszawie	Warszawa
Poland	Biogenes NZOZ	Wroclaw
Poland	Synexus Polska Sp. z o.o	Wroclaw
Russian Federation	Sverdlovsk Regional Clinical Hospital #1	Ekaterinburg
Russian Federation	Krasnoyarsk Medical Academy	Krasnoyarsk
Russian Federation	Practicheskaya Meditsina, Ltd	Moscow
Russian Federation	State Healthcare Institution of Moscow City Clinical Hospital #15 n.a. O.M. Filatov	Moscow
Russian Federation	Republican Hospital n.a. V.A. Baranov	Petrozavodsk
Russian Federation	Smolensk State Medical University (SSMU)	Smolensk
Russian Federation	St. Petersburg State Healthcare Institution "Consultative diagnostic center #85	St Petersburg
Russian Federation	Medical Research Institute, LLC	St. Petersburg
Russian Federation	Municipal Healthcare Institution "Emergency Clinical Hospital n.a. N.V. Soloviev	Yaroslavl
Russian Federation	MBI "Central City Clinical Hospital #6	Yekaterinburg
South Africa	Dr CI Louw	Cape Town
South Africa	Dr S Nayiager	Durban
South Africa	Wits Donald Gordon Clinical Trial Site	Johannesburg
South Africa	Drs Dindar and Partners	Mpumalanga
South Africa	Private Practice - Cathy Spargo	Pinelands
South Africa	Emmed Research	Pretoria
South Africa	Jakaranda Hospital Pretoria	Pretoria
South Africa	Winelands Rheumatology Centre	Stellenbosch
Spain	Hospital La Paz	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Regional Universitario de Málaga	Malaga
United Kingdom	Royal Sussex County Hospital	Brighton
United Kingdom	Harrogate District NHS Foundation Trust	Harrogate
United Kingdom	Wirral University Teaching Hospital NHS Foundation Trust	Merseyside
United States	Dream Team Clinical Research	Anaheim	California
United States	Texas Physicians Medical Research Group	Arlington	Texas
United States	Montefiore Medical Center	Bronx	New York
United States	IMMUNOe International Research Centers	Centennial	Colorado
United States	Low Country Rheumatology	Charleston	South Carolina
United States	DJL Clinical Research	Charlotte	North Carolina
United States	Metroplex Clinical Research Center	Dallas	Texas
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Rheumatic Disease Center	Glendale	Wisconsin
United States	North Shore University Hospital	Great Neck	New York
United States	Pioneer Research Solutions Inc	Houston	Texas
United States	Arthritis Clinic	Jackson	Tennessee
United States	NEA Baptist Clinic	Jonesboro	Arkansas
United States	Hope Clinical Research	Kissimmee	Florida
United States	Advanced Medical Research	Lakewood	California
United States	Bluegrass Community Research, Inc	Lexington	Kentucky
United States	Arthritis Center of Nebraska	Lincoln	Nebraska
United States	Pro Health Partners	Long Beach	California
United States	Pacific Arthritis Center Medical Group	Omaha	Nebraska
United States	Rheumatoid Arthritis Investigational Network	Omaha	Nebraska
United States	Gundersen Lutheran Medical Center	Onalaska	Wisconsin
United States	St. Joseph Hospital of Orange	Orange	California
United States	Advanced Medical Research, Inc	Orlando	Florida
United States	Desert Medical Advances	Palm Desert	California
United States	Arizona Research Center	Phoenix	Arizona
United States	Elite Clinical Studies	Phoenix	Arizona
United States	Kaiser Permanente - CA	Richmond	California
United States	Med Investigators, Inc	Roseville	California
United States	St. Louis Center for Clinical Research	Saint Louis	Missouri
United States	Allergy & Rheumatology Associates LLC	Saint Petersburg	Florida
United States	Troum Medical Associates	Santa Monica	California
United States	Arthritis Northwest Rheumatology PLLC	Spokane	Washington
United States	HealthPoint Medical Group	Tampa	Florida
United States	Inland Rheumatology Clinical Trials Inc	Upland	California
United States	The Center for Rheumatology and Bone Research	Wheaton	Maryland
United States	PMG Research of Wilmington LLC	Wilmington	North Carolina
United States	Clinical Pharmacology Study Group	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Coherus Biosciences, Inc.	Daiichi Sankyo Co., Ltd.

Countries where clinical trial is conducted

United States,  Belarus,  France,  Germany,  Hungary,  Israel,  Japan,  Poland,  Russian Federation,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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