A Study Comparing SB4 to Enbrel® in Subjects With Moderate to Severe Rheumatoid Arthritis Despite Methotrexate Therapy

Sponsor

Samsung Bioepis Co., Ltd. (Industry)

Overall Status

Completed

CT.gov ID

NCT01895309

Collaborator

(none)

596

Enrollment

Locations

Arms

Duration (Months)

298

Patients Per Site

10.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomized, double-blind, parallel group, multicentre clinical study to evaluate the efficacy, safety, pharmacokinetics and immunogenicity of SB4 compared to Enbrel in subjects with moderate to severe Rheumatoid Arthritis (RA) despite Methotrexate (MTX) therapy. In some countries, after 52 weeks of treatment with either SB4 or Enbrel, subjects will be enrolled into an open label extension period. Subjects will receive SB4 for an additional 48 weeks.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Enbrel (etanercept) Drug: SB4 (proposed biosimilar to etanercept)	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

596 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomised, Double-blind, Parallel Group, Multicentre Clinical Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Immunogenicity of SB4 Compared to Enbrel® in Subjects With Moderate to Severe Rheumatoid Arthritis Despite Methotrexate Therapy

Study Start Date :

Jun 1, 2013

Actual Primary Completion Date :

Apr 1, 2014

Actual Study Completion Date :

Oct 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SB4 (proposed biosimilar to etanercept) SB4 50 mg/week via subcutaneous injection	Drug: SB4 (proposed biosimilar to etanercept)
Active Comparator: Enbrel (etanercept) Enbrel 50 mg/week via subcutaneous injection	Drug: Enbrel (etanercept)

Arm

Intervention/Treatment

Experimental: SB4 (proposed biosimilar to etanercept)

SB4 50 mg/week via subcutaneous injection

Drug: SB4 (proposed biosimilar to etanercept)

Active Comparator: Enbrel (etanercept)

Enbrel 50 mg/week via subcutaneous injection

Drug: Enbrel (etanercept)

Outcome Measures

Primary Outcome Measures

American College of Rheumatology 20% Response Criteria (ACR20) [Week 24]

Secondary Outcome Measures

ACR20 [Week 52]
American College of Rheumatology 50% Response Criteria (ACR50) [Week 24, Week 52]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosed as having RA according to the revised 1987 ACR criteria for at least 6 months but not exceeding 15 years prior to Screening
Have moderate to severe active disease despite MTX therapy defined as having more than or equal to six swollen joints and more than or equal to six tender joints and either erythrocyte sedimentation rate (ESR, Westergren) ≥ 28 mm/h or serum C-reactive protein ≥ 1.0 mg/dL
Must have been treated with MTX for at least 6 months prior to Randomisation and on a stable dose of MTX 10-25 mg/week given at least 4 weeks prior to Screening
Female subjects who are not pregnant or nursing at Screening and who are not planning to become pregnant from Screening until 2 months after the last dose of investigational product

Exclusion Criteria:

Have been treated previously with any biological agents including any tumour necrosis factor inhibitor
Have a known hypersensitivity to human immunoglobulin proteins or other components of Enbrel or SB4
Have a positive serological test for hepatitis B or hepatitis C or have a known history of infection with human immunodeficiency virus
Have a current diagnosis of active tuberculosis
Have had a serious infection or have been treated with intravenous antibiotics for an infection within 8 weeks or oral antibiotics within 2 weeks prior to Randomisation.
Have any of the following conditions

Other inflammatory or rheumatic diseases.
History of any malignancy within the previous 5 years prior to Screening
History of lymphoproliferative disease including lymphoma.
History of congestive heart failure
Physical incapacitation (ACR functional Class IV or wheelchair-/bed-bound).
History of demyelinating disorders.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site	Kielce		Poland
2	Investigational Site	Southampton	Hampshire	United Kingdom

Sponsors and Collaborators

Samsung Bioepis Co., Ltd.

Investigators

Principal Investigator: Jiri Vencovsky, M.D., Ph.D., Charles University, Czech Republic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Samsung Bioepis Co., Ltd.

ClinicalTrials.gov Identifier:

NCT01895309

Other Study ID Numbers:

SB4-G31-RA

First Posted:

Jul 10, 2013

Last Update Posted:

Aug 17, 2017

Last Verified:

Dec 1, 2015

Keywords provided by Samsung Bioepis Co., Ltd.

Rheumatoid Arthritis

Etanercept

Biosimilar

Additional relevant MeSH terms:

Arthritis

Arthritis, Rheumatoid

Etanercept

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail

Arm/Group Title	SB4 (Proposed Biosimilar to Etanercept)	Enbrel (Etanercept)
Arm/Group Description	SB4 50 mg/week via subcutaneous injection	Enbrel 50 mg/week via subcutaneous injection
Period Title: Overall Study
STARTED	299	297
COMPLETED	259	246
NOT COMPLETED	40	51

Baseline Characteristics

Arm/Group Title	SB4 (Proposed Biosimilar to Etanercept)	Enbrel (Etanercept)	Total
Arm/Group Description	SB4 50 mg/week via subcutaneous injection	Enbrel 50 mg/week via subcutaneous injection	Total of all reporting groups
Overall Participants	299	297	596
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.1 (11.72)	51.6 (11.63)	51.8 (11.67)
Sex: Female, Male (Count of Participants)
Female	249 83.3%	253 85.2%	502 84.2%
Male	50 16.7%	44 14.8%	94 15.8%

Outcome Measures

1. Primary Outcome

Title	American College of Rheumatology 20% Response Criteria (ACR20)
Description
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	SB4 (Proposed Biosimilar to Etanercept)	Enbrel (Etanercept)
Arm/Group Description	SB4 50 mg/week via subcutaneous injection	Enbrel 50 mg/week via subcutaneous injection
Measure Participants	247	236
Number [percentage of participants]	78.1 26.1%	80.5 27.1%

2. Secondary Outcome

Title	ACR20
Description
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	SB4 (Proposed Biosimilar to Etanercept)	Enbrel (Etanercept)
Arm/Group Description	SB4 50 mg/week via subcutaneous injection	Enbrel 50 mg/week via subcutaneous injection
Measure Participants	224	216
Number [percentage of participants]	80.8 27%	81.5 27.4%

3. Secondary Outcome

Title	American College of Rheumatology 50% Response Criteria (ACR50)
Description
Time Frame	Week 24, Week 52

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	SB4 (Proposed Biosimilar to Etanercept) at Week 24	Enbrel (Etanercept) at Week 24	SB4 (Proposed Biosimilar to Etanercept) at Week 52	Enbrel (Etanercept) at Week 52
Arm/Group Description	SB4 50 mg/week via subcutaneous injection SB4 (proposed biosimilar to etanercept)	Enbrel 50 mg/week via subcutaneous injection Enbrel (etanercept)	SB4 50 mg/week via subcutaneous injection SB4 (proposed biosimilar to etanercept)	Enbrel 50 mg/week via subcutaneous injection Enbrel (etanercept)
Measure Participants	247	236	224	216
Number [percentage of participants]	46.2 15.5%	42.4 14.3%	58.5 9.8%	53.2 NaN

Adverse Events

	SB4 (Proposed Biosimilar to Etanercept)		Enbrel (Etanercept)
Time Frame
Adverse Event Reporting Description

Arm/Group Title	SB4 (Proposed Biosimilar to Etanercept)		Enbrel (Etanercept)
Arm/Group Description	SB4 50 mg/week via subcutaneous injection SB4 (proposed biosimilar to etanercept)		Enbrel 50 mg/week via subcutaneous injection Enbrel (etanercept)
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	SB4 (Proposed Biosimilar to Etanercept)		Enbrel (Etanercept)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/299 (6%)		15/297 (5.1%)
Blood and lymphatic system disorders
Neutropenia	0/299 (0%)	0	1/297 (0.3%)	1
Cardiac disorders
Acute Myocardial Infarction	1/299 (0.3%)	1	0/297 (0%)	0
Atrial Fibrillation	1/299 (0.3%)	1	0/297 (0%)	0
Cardiopulmonary Failure	1/299 (0.3%)	1	0/297 (0%)	0
Coronary Artery Disease	0/299 (0%)	0	1/297 (0.3%)	1
Eye disorders
Chorioretinopathy	0/299 (0%)	0	1/297 (0.3%)	1
Gastrointestinal disorders
Enterocolitis	0/299 (0%)	0	1/297 (0.3%)	1
Gastritis	0/299 (0%)	0	1/297 (0.3%)	1
Gastrooesophageal Reflux Disease	0/299 (0%)	0	1/297 (0.3%)	1
General disorders
Device Failure	1/299 (0.3%)	1	0/297 (0%)	0
Hepatobiliary disorders
Bile Duct Stone	1/299 (0.3%)	2	0/297 (0%)	0
Cholangitis	1/299 (0.3%)	1	0/297 (0%)	0
Cholecystitis	1/299 (0.3%)	1	0/297 (0%)	0
Cholelithiasis	1/299 (0.3%)	1	0/297 (0%)	0
Gallbladder Perforation	1/299 (0.3%)	1	0/297 (0%)	0
Infections and infestations
Liver Abscess	1/299 (0.3%)	1	0/297 (0%)	0
Peritonitis	1/299 (0.3%)	1	0/297 (0%)	0
Appendicitis	0/299 (0%)	0	1/297 (0.3%)	1
Cellulitis	0/299 (0%)	0	2/297 (0.7%)	2
Erysipelas	0/299 (0%)	0	1/297 (0.3%)	1
Pneumonia	0/299 (0%)	0	1/297 (0.3%)	1
Injury, poisoning and procedural complications
Femoral Neck Fracture	0/299 (0%)	0	1/297 (0.3%)	1
Musculoskeletal and connective tissue disorders
Rheumatoid Arthritis	1/299 (0.3%)	1	1/297 (0.3%)	1
Still'S Disease Adult Onset	1/299 (0.3%)	2	0/297 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma Gastric	1/299 (0.3%)	1	0/297 (0%)	0
Breast Cancer	1/299 (0.3%)	1	0/297 (0%)	0
Lung Cancer Metastatic	1/299 (0.3%)	1	0/297 (0%)	0
Invasive Ductal Breast Carcinoma	0/299 (0%)	0	1/297 (0.3%)	1
Nervous system disorders
Syncope	1/299 (0.3%)	1	0/297 (0%)	0
Reproductive system and breast disorders
Ovarian Cyst	1/299 (0.3%)	1	0/297 (0%)	0
Uterine Polyp	1/299 (0.3%)	1	0/297 (0%)	0
Vaginal Prolapse	1/299 (0.3%)	1	0/297 (0%)	0
Skin and subcutaneous tissue disorders
Psoriasis	1/299 (0.3%)	1	0/297 (0%)	0
Vascular disorders
Hypertensive Crisis	0/299 (0%)	0	1/297 (0.3%)	1
Other (Not Including Serious) Adverse Events
	SB4 (Proposed Biosimilar to Etanercept)		Enbrel (Etanercept)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	175/299 (58.5%)		179/297 (60.3%)
Blood and lymphatic system disorders
Leukopenia	6/299 (2%)	7	3/297 (1%)	4
Anaemia	5/299 (1.7%)	5	3/297 (1%)	4
Neutropenia	4/299 (1.3%)	4	5/297 (1.7%)	7
Thrombocytopenia	3/299 (1%)	3	0/297 (0%)	0
Lymphopenia	2/299 (0.7%)	2	4/297 (1.3%)	4
Anaemia Of Chronic Disease	1/299 (0.3%)	1	0/297 (0%)	0
Lymphadenopathy	0/299 (0%)	0	3/297 (1%)	4
Cardiac disorders
Tachycardia	2/299 (0.7%)	2	1/297 (0.3%)	1
Acute Myocardial Infarction	1/299 (0.3%)	1	0/297 (0%)	0
Atrial Fibrillation	1/299 (0.3%)	1	0/297 (0%)	0
Cardiopulmonary Failure	1/299 (0.3%)	1	0/297 (0%)	0
Cardiac Failure Congestive	0/299 (0%)	0	1/297 (0.3%)	1
Cardiovascular Insufficiency	0/299 (0%)	0	1/297 (0.3%)	1
Coronary Artery Disease	0/299 (0%)	0	1/297 (0.3%)	1
Mitral Valve Prolapse	0/299 (0%)	0	1/297 (0.3%)	1
Palpitations	0/299 (0%)	0	2/297 (0.7%)	2
Ear and labyrinth disorders
Vertigo	3/299 (1%)	3	1/297 (0.3%)	1
Hypoacusis	1/299 (0.3%)	1	0/297 (0%)	0
Ear Pain	0/299 (0%)	0	1/297 (0.3%)	1
External Ear Inflammation	0/299 (0%)	0	2/297 (0.7%)	2
Tinnitus	0/299 (0%)	0	1/297 (0.3%)	1
Endocrine disorders
Goitre	1/299 (0.3%)	1	1/297 (0.3%)	1
Thyroid Cyst	0/299 (0%)	0	1/297 (0.3%)	1
Eye disorders
Eyelid Oedema	2/299 (0.7%)	3	0/297 (0%)	0
Conjunctival Haemorrhage	1/299 (0.3%)	1	1/297 (0.3%)	1
Conjunctivitis	1/299 (0.3%)	1	0/297 (0%)	0
Dry Eye	1/299 (0.3%)	1	1/297 (0.3%)	1
Eye Irritation	1/299 (0.3%)	1	0/297 (0%)	0
Eyelid Ptosis	1/299 (0.3%)	1	0/297 (0%)	0
Vision Blurred	1/299 (0.3%)	1	0/297 (0%)	0
Cataract	0/299 (0%)	0	1/297 (0.3%)	1
Chorioretinopathy	0/299 (0%)	0	1/297 (0.3%)	1
Presbyopia	0/299 (0%)	0	1/297 (0.3%)	1
Gastrointestinal disorders
Diarrhoea	5/299 (1.7%)	5	7/297 (2.4%)	8
Abdominal Pain Upper	4/299 (1.3%)	5	4/297 (1.3%)	4
Nausea	4/299 (1.3%)	8	1/297 (0.3%)	2
Abdominal Pain	2/299 (0.7%)	2	3/297 (1%)	4
Dyspepsia	2/299 (0.7%)	2	4/297 (1.3%)	4
Abdominal Pain Lower	1/299 (0.3%)	1	0/297 (0%)	0
Constipation	1/299 (0.3%)	1	0/297 (0%)	0
Diverticulum Intestinal	1/299 (0.3%)	1	1/297 (0.3%)	1
Enterocele	1/299 (0.3%)	1	0/297 (0%)	0
Gastrooesophageal Reflux Disease	1/299 (0.3%)	1	2/297 (0.7%)	2
Irritable Bowel Syndrome	1/299 (0.3%)	1	0/297 (0%)	0
Parotid Gland Inflammation	1/299 (0.3%)	1	0/297 (0%)	0
Colitis	0/299 (0%)	0	1/297 (0.3%)	1
Dry Mouth	0/299 (0%)	0	1/297 (0.3%)	1
Enterocolitis	0/299 (0%)	0	1/297 (0.3%)	1
Flatulence	0/299 (0%)	0	2/297 (0.7%)	2
Gastric Ulcer	0/299 (0%)	0	1/297 (0.3%)	1
Gastritis	0/299 (0%)	0	4/297 (1.3%)	5
Gastrointestinal Disorder	0/299 (0%)	0	1/297 (0.3%)	1
Haemorrhoids	0/299 (0%)	0	2/297 (0.7%)	2
Portal Hypertensive Gastropathy	0/299 (0%)	0	1/297 (0.3%)	1
Reflux Gastritis	0/299 (0%)	0	1/297 (0.3%)	1
Retching	0/299 (0%)	0	1/297 (0.3%)	1
Stomatitis	0/299 (0%)	0	1/297 (0.3%)	1
Vomiting	0/299 (0%)	0	3/297 (1%)	3
General disorders
Injection Site Erythema	6/299 (2%)	16	33/297 (11.1%)	85
Influenza Like Illness	3/299 (1%)	5	1/297 (0.3%)	1
Oedema Peripheral	3/299 (1%)	3	3/297 (1%)	4
Asthenia	2/299 (0.7%)	2	5/297 (1.7%)	5
Chest Pain	2/299 (0.7%)	3	2/297 (0.7%)	3
Chills	2/299 (0.7%)	2	0/297 (0%)	0
Fatigue	2/299 (0.7%)	2	4/297 (1.3%)	4
Injection Site Rash	2/299 (0.7%)	2	6/297 (2%)	11
Pain	2/299 (0.7%)	2	1/297 (0.3%)	1
Spinal Pain	2/299 (0.7%)	3	1/297 (0.3%)	1
Device Failure	1/299 (0.3%)	1	0/297 (0%)	0
Injection Site Haematoma	1/299 (0.3%)	1	0/297 (0%)	0
Injection Site Hypersensitivity	1/299 (0.3%)	1	2/297 (0.7%)	10
Injection Site Pruritus	1/299 (0.3%)	1	4/297 (1.3%)	6
Injection Site Reaction	1/299 (0.3%)	1	8/297 (2.7%)	13
Pyrexia	1/299 (0.3%)	1	2/297 (0.7%)	3
Application Site Erythema	0/299 (0%)	0	3/297 (1%)	18
Application Site Reaction	0/299 (0%)	0	1/297 (0.3%)	1
Face Oedema	0/299 (0%)	0	1/297 (0.3%)	1
Feeling Hot	0/299 (0%)	0	1/297 (0.3%)	1
Injection Site Bruising	0/299 (0%)	0	1/297 (0.3%)	1
Injection Site Dermatitis	0/299 (0%)	0	1/297 (0.3%)	2
Injection Site Inflammation	0/299 (0%)	0	2/297 (0.7%)	2
Injection Site Oedema	0/299 (0%)	0	3/297 (1%)	6
Injection Site Pain	0/299 (0%)	0	1/297 (0.3%)	1
Injection Site Swelling	0/299 (0%)	0	1/297 (0.3%)	1
Malaise	0/299 (0%)	0	2/297 (0.7%)	3
Soft Tissue Inflammation	0/299 (0%)	0	1/297 (0.3%)	1
Hepatobiliary disorders
Cholelithiasis	4/299 (1.3%)	4	0/297 (0%)	0
Liver Disorder	3/299 (1%)	3	0/297 (0%)	0
Cholecystitis Chronic	2/299 (0.7%)	3	0/297 (0%)	0
Bile Duct Stone	1/299 (0.3%)	2	0/297 (0%)	0
Biliary Colic	1/299 (0.3%)	1	0/297 (0%)	0
Cholangitis	1/299 (0.3%)	1	0/297 (0%)	0
Cholecystitis	1/299 (0.3%)	1	0/297 (0%)	0
Gallbladder Perforation	1/299 (0.3%)	1	0/297 (0%)	0
Hypertransaminasaemia	1/299 (0.3%)	1	0/297 (0%)	0
Immune system disorders
Allergy To Arthropod Bite	1/299 (0.3%)	1	0/297 (0%)	0
Hypersensitivity	0/299 (0%)	0	1/297 (0.3%)	1
Infections and infestations
Upper Respiratory Tract Infection	24/299 (8%)	28	16/297 (5.4%)	18
Nasopharyngitis	15/299 (5%)	17	16/297 (5.4%)	17
Viral Infection	7/299 (2.3%)	7	5/297 (1.7%)	5
Bronchitis	6/299 (2%)	6	6/297 (2%)	6
Rhinitis	6/299 (2%)	6	4/297 (1.3%)	5
Pharyngitis	5/299 (1.7%)	5	8/297 (2.7%)	9
Urinary Tract Infection	5/299 (1.7%)	5	7/297 (2.4%)	9
Oral Herpes	4/299 (1.3%)	7	5/297 (1.7%)	6
Herpes Zoster	3/299 (1%)	5	1/297 (0.3%)	1
Asymptomatic Bacteriuria	2/299 (0.7%)	3	0/297 (0%)	0
Ear Infection	2/299 (0.7%)	2	0/297 (0%)	0
Otitis Externa	2/299 (0.7%)	2	0/297 (0%)	0
Pharyngotonsillitis	2/299 (0.7%)	2	1/297 (0.3%)	1
Pneumonia	2/299 (0.7%)	2	1/297 (0.3%)	1
Sinusitis	2/299 (0.7%)	2	1/297 (0.3%)	1
Viral Upper Respiratory Tract Infection	2/299 (0.7%)	2	3/297 (1%)	3
Acute Tonsillitis	1/299 (0.3%)	1	0/297 (0%)	0
Bacteriuria	1/299 (0.3%)	1	0/297 (0%)	0
Cellulitis	1/299 (0.3%)	1	2/297 (0.7%)	2
Chronic Tonsillitis	1/299 (0.3%)	1	0/297 (0%)	0
Diverticulitis	1/299 (0.3%)	1	0/297 (0%)	0
Erysipelas	1/299 (0.3%)	1	1/297 (0.3%)	1
Fungal Infection	1/299 (0.3%)	1	0/297 (0%)	0
Furuncle	1/299 (0.3%)	1	0/297 (0%)	0
Gastroenteritis	1/299 (0.3%)	1	2/297 (0.7%)	2
Herpes Simplex	1/299 (0.3%)	1	2/297 (0.7%)	2
Liver Abscess	1/299 (0.3%)	1	0/297 (0%)	0
Localised Infection	1/299 (0.3%)	1	0/297 (0%)	0
Lyme Disease	1/299 (0.3%)	1	0/297 (0%)	0
Otitis Media	1/299 (0.3%)	1	1/297 (0.3%)	1
Peritonitis	1/299 (0.3%)	1	0/297 (0%)	0
Pharyngitis Bacterial	1/299 (0.3%)	1	0/297 (0%)	0
Pyelonephritis	1/299 (0.3%)	1	1/297 (0.3%)	1
Rash Pustular	1/299 (0.3%)	1	0/297 (0%)	0
Respiratory Tract Infection	1/299 (0.3%)	1	1/297 (0.3%)	1
Tinea Pedis	1/299 (0.3%)	1	1/297 (0.3%)	1
Tinea Versicolour	1/299 (0.3%)	1	1/297 (0.3%)	1
Tonsillitis	1/299 (0.3%)	1	2/297 (0.7%)	2
Tooth Infection	1/299 (0.3%)	1	0/297 (0%)	0
Tracheobronchitis	1/299 (0.3%)	1	0/297 (0%)	0
Acute Sinusitis	0/299 (0%)	0	1/297 (0.3%)	1
Appendicitis	0/299 (0%)	0	1/297 (0.3%)	1
Eczema Infected	0/299 (0%)	0	1/297 (0.3%)	1
Gingivitis	0/299 (0%)	0	1/297 (0.3%)	2
Herpes Virus Infection	0/299 (0%)	0	1/297 (0.3%)	2
Influenza	0/299 (0%)	0	1/297 (0.3%)	1
Laryngitis	0/299 (0%)	0	1/297 (0.3%)	1
Lobar Pneumonia	0/299 (0%)	0	1/297 (0.3%)	1
Nail Candida	0/299 (0%)	0	1/297 (0.3%)	1
Onychomycosis	0/299 (0%)	0	1/297 (0.3%)	1
Periodontitis	0/299 (0%)	0	1/297 (0.3%)	1
Peritonitis Bacterial	0/299 (0%)	0	1/297 (0.3%)	1
Pulpitis Dental	0/299 (0%)	0	1/297 (0.3%)	1
Sialoadenitis	0/299 (0%)	0	1/297 (0.3%)	1
Viral Rhinitis	0/299 (0%)	0	1/297 (0.3%)	2
Vulvovaginal Candidiasis	0/299 (0%)	0	1/297 (0.3%)	1
Injury, poisoning and procedural complications
Contusion	2/299 (0.7%)	3	1/297 (0.3%)	1
Head Injury	2/299 (0.7%)	2	0/297 (0%)	0
Arthropod Bite	1/299 (0.3%)	1	0/297 (0%)	0
Hand Fracture	1/299 (0.3%)	1	0/297 (0%)	0
Joint Dislocation	1/299 (0.3%)	1	0/297 (0%)	0
Joint Injury	1/299 (0.3%)	1	0/297 (0%)	0
Ligament Sprain	1/299 (0.3%)	1	1/297 (0.3%)	1
Muscle Strain	1/299 (0.3%)	1	0/297 (0%)	0
Traumatic Fracture	1/299 (0.3%)	1	0/297 (0%)	0
Fall	0/299 (0%)	0	1/297 (0.3%)	1
Femoral Neck Fracture	0/299 (0%)	0	1/297 (0.3%)	1
Fibula Fracture	0/299 (0%)	0	1/297 (0.3%)	1
Injection Related Reaction	0/299 (0%)	0	1/297 (0.3%)	2
Injury	0/299 (0%)	0	1/297 (0.3%)	2
Limb Injury	0/299 (0%)	0	1/297 (0.3%)	2
Lumbar Vertebral Fracture	0/299 (0%)	0	2/297 (0.7%)	2
Thermal Burn	0/299 (0%)	0	1/297 (0.3%)	1
Investigations
Alanine Aminotransferase Increased	18/299 (6%)	25	17/297 (5.7%)	26
Aspartate Aminotransferase Increased	8/299 (2.7%)	13	9/297 (3%)	10
Gamma-Glutamyltransferase Increased	5/299 (1.7%)	11	5/297 (1.7%)	6
Lymphocyte Count Decreased	4/299 (1.3%)	4	6/297 (2%)	8
Transaminases Increased	4/299 (1.3%)	5	4/297 (1.3%)	4
Blood Pressure Increased	3/299 (1%)	4	3/297 (1%)	3
Liver Function Test Abnormal	3/299 (1%)	4	2/297 (0.7%)	2
Blood Alkaline Phosphatase Increased	2/299 (0.7%)	4	0/297 (0%)	0
Blood Glucose Increased	2/299 (0.7%)	2	0/297 (0%)	0
Hepatic Enzyme Increased	2/299 (0.7%)	4	0/297 (0%)	0
Neutrophil Count Decreased	2/299 (0.7%)	2	1/297 (0.3%)	1
White Blood Cell Count Decreased	2/299 (0.7%)	2	1/297 (0.3%)	1
Blood Urine Present	1/299 (0.3%)	1	0/297 (0%)	0
Haemoglobin Decreased	1/299 (0.3%)	1	0/297 (0%)	0
Neutrophil Count Increased	1/299 (0.3%)	1	0/297 (0%)	0
Nitrite Urine Present	1/299 (0.3%)	1	0/297 (0%)	0
Urine Analysis Abnormal	1/299 (0.3%)	1	0/297 (0%)	0
Weight Increased	1/299 (0.3%)	1	0/297 (0%)	0
Blood Calcium Decreased	0/299 (0%)	0	1/297 (0.3%)	2
Blood Phosphorus Decreased	0/299 (0%)	0	2/297 (0.7%)	3
Lymphocyte Count Abnormal	0/299 (0%)	0	1/297 (0.3%)	1
Lymphocyte Count Increased	0/299 (0%)	0	1/297 (0.3%)	1
Platelet Count Decreased	0/299 (0%)	0	1/297 (0.3%)	3
Platelet Count Increased	0/299 (0%)	0	1/297 (0.3%)	1
Metabolism and nutrition disorders
Hypokalaemia	1/299 (0.3%)	1	0/297 (0%)	0
Dyslipidaemia	0/299 (0%)	0	1/297 (0.3%)	1
Hypercholesterolaemia	0/299 (0%)	0	2/297 (0.7%)	2
Hypoglycaemia	0/299 (0%)	0	1/297 (0.3%)	1
Metabolic Syndrome	0/299 (0%)	0	1/297 (0.3%)	1
Type 2 Diabetes Mellitus	0/299 (0%)	0	1/297 (0.3%)	1
Musculoskeletal and connective tissue disorders
Rheumatoid Arthritis	9/299 (3%)	10	10/297 (3.4%)	11
Arthralgia	4/299 (1.3%)	5	5/297 (1.7%)	10
Back Pain	4/299 (1.3%)	5	4/297 (1.3%)	4
Arthritis	2/299 (0.7%)	2	1/297 (0.3%)	1
Musculoskeletal Pain	2/299 (0.7%)	2	1/297 (0.3%)	1
Pain In Extremity	2/299 (0.7%)	2	2/297 (0.7%)	2
Periarthritis	2/299 (0.7%)	2	0/297 (0%)	0
Bursitis	1/299 (0.3%)	1	0/297 (0%)	0
Fracture Delayed Union	1/299 (0.3%)	1	0/297 (0%)	0
Groin Pain	1/299 (0.3%)	2	0/297 (0%)	0
Musculoskeletal Chest Pain	1/299 (0.3%)	1	0/297 (0%)	0
Myalgia	1/299 (0.3%)	1	0/297 (0%)	0
Neck Pain	1/299 (0.3%)	1	1/297 (0.3%)	1
Osteoarthritis	1/299 (0.3%)	1	2/297 (0.7%)	2
Sjogren'S Syndrome	1/299 (0.3%)	1	0/297 (0%)	0
Still'S Disease Adult Onset	1/299 (0.3%)	2	0/297 (0%)	0
Synovitis	1/299 (0.3%)	1	0/297 (0%)	0
Tenosynovitis	1/299 (0.3%)	1	0/297 (0%)	0
Bone Pain	0/299 (0%)	0	1/297 (0.3%)	1
Enthesopathy	0/299 (0%)	0	1/297 (0.3%)	2
Fibromyalgia	0/299 (0%)	0	1/297 (0.3%)	1
Intervertebral Disc Disorder	0/299 (0%)	0	1/297 (0.3%)	1
Joint Swelling	0/299 (0%)	0	1/297 (0.3%)	1
Lumbar Spinal Stenosis	0/299 (0%)	0	1/297 (0.3%)	1
Muscle Spasms	0/299 (0%)	0	1/297 (0.3%)	1
Nuchal Rigidity	0/299 (0%)	0	1/297 (0.3%)	1
Osteopenia	0/299 (0%)	0	1/297 (0.3%)	1
Osteoporosis	0/299 (0%)	0	2/297 (0.7%)	2
Osteoporotic Fracture	0/299 (0%)	0	1/297 (0.3%)	1
Periostitis	0/299 (0%)	0	1/297 (0.3%)	1
Spinal Deformity	0/299 (0%)	0	1/297 (0.3%)	1
Spondylolisthesis	0/299 (0%)	0	1/297 (0.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine Leiomyoma	2/299 (0.7%)	2	1/297 (0.3%)	1
Adenocarcinoma Gastric	1/299 (0.3%)	1	0/297 (0%)	0
Basal Cell Carcinoma	1/299 (0.3%)	1	0/297 (0%)	0
Breast Cancer	1/299 (0.3%)	1	0/297 (0%)	0
Haemangioma Of Liver	1/299 (0.3%)	1	0/297 (0%)	0
Lung Cancer Metastatic	1/299 (0.3%)	1	0/297 (0%)	0
Melanocytic Naevus	1/299 (0.3%)	1	0/297 (0%)	0
Breast Fibroma	0/299 (0%)	0	1/297 (0.3%)	1
Invasive Ductal Breast Carcinoma	0/299 (0%)	0	1/297 (0.3%)	1
Neoplasm	0/299 (0%)	0	1/297 (0.3%)	1
Pyogenic Granuloma	0/299 (0%)	0	1/297 (0.3%)	1
Nervous system disorders
Headache	13/299 (4.3%)	15	8/297 (2.7%)	16
Dizziness	2/299 (0.7%)	3	7/297 (2.4%)	7
Syncope	2/299 (0.7%)	2	1/297 (0.3%)	1
Anosmia	1/299 (0.3%)	1	0/297 (0%)	0
Disturbance In Attention	1/299 (0.3%)	1	0/297 (0%)	0
Dystonia	1/299 (0.3%)	1	0/297 (0%)	0
Hypoaesthesia	1/299 (0.3%)	2	1/297 (0.3%)	1
Migraine	1/299 (0.3%)	1	0/297 (0%)	0
Parosmia	1/299 (0.3%)	1	0/297 (0%)	0
Radiculopathy	1/299 (0.3%)	1	0/297 (0%)	0
Sciatica	1/299 (0.3%)	1	2/297 (0.7%)	3
Stupor	1/299 (0.3%)	1	0/297 (0%)	0
Aphasia	0/299 (0%)	0	1/297 (0.3%)	1
Balance Disorder	0/299 (0%)	0	1/297 (0.3%)	1
Hypertensive Encephalopathy	0/299 (0%)	0	1/297 (0.3%)	1
Loss Of Consciousness	0/299 (0%)	0	1/297 (0.3%)	1
Lumbar Radiculopathy	0/299 (0%)	0	1/297 (0.3%)	1
Paraesthesia	0/299 (0%)	0	1/297 (0.3%)	1
Somnolence	0/299 (0%)	0	2/297 (0.7%)	2
Tremor	0/299 (0%)	0	1/297 (0.3%)	1
Psychiatric disorders
Insomnia	2/299 (0.7%)	2	1/297 (0.3%)	1
Sleep Disorder	2/299 (0.7%)	2	0/297 (0%)	0
Anxiety	1/299 (0.3%)	1	0/297 (0%)	0
Anxiety Disorder	1/299 (0.3%)	1	0/297 (0%)	0
Initial Insomnia	1/299 (0.3%)	1	0/297 (0%)	0
Tachyphrenia	1/299 (0.3%)	1	0/297 (0%)	0
Neurosis	0/299 (0%)	0	1/297 (0.3%)	1
Renal and urinary disorders
Haematuria	2/299 (0.7%)	3	2/297 (0.7%)	3
Calculus Bladder	1/299 (0.3%)	1	0/297 (0%)	0
Renal Cyst	1/299 (0.3%)	1	0/297 (0%)	0
Urinary Tract Inflammation	1/299 (0.3%)	1	0/297 (0%)	0
Reproductive system and breast disorders
Amenorrhoea	1/299 (0.3%)	1	0/297 (0%)	0
Breast Mass	1/299 (0.3%)	1	0/297 (0%)	0
Breast Pain	1/299 (0.3%)	1	0/297 (0%)	0
Breast Swelling	1/299 (0.3%)	1	0/297 (0%)	0
Cervical Polyp	1/299 (0.3%)	1	0/297 (0%)	0
Dysmenorrhoea	1/299 (0.3%)	1	0/297 (0%)	0
Ovarian Cyst	1/299 (0.3%)	1	0/297 (0%)	0
Uterine Polyp	1/299 (0.3%)	1	0/297 (0%)	0
Vaginal Prolapse	1/299 (0.3%)	1	0/297 (0%)	0
Vulvovaginal Pruritus	1/299 (0.3%)	1	0/297 (0%)	0
Breast Induration	0/299 (0%)	0	1/297 (0.3%)	1
Menopausal Symptoms	0/299 (0%)	0	1/297 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	4/299 (1.3%)	4	10/297 (3.4%)	11
Oropharyngeal Pain	4/299 (1.3%)	5	1/297 (0.3%)	1
Upper Respiratory Tract Inflammation	2/299 (0.7%)	2	1/297 (0.3%)	1
Chronic Obstructive Pulmonary Disease	1/299 (0.3%)	1	0/297 (0%)	0
Nasal Congestion	1/299 (0.3%)	1	0/297 (0%)	0
Productive Cough	1/299 (0.3%)	1	0/297 (0%)	0
Rhinitis Allergic	1/299 (0.3%)	1	0/297 (0%)	0
Rhinorrhoea	1/299 (0.3%)	1	0/297 (0%)	0
Sneezing	1/299 (0.3%)	1	0/297 (0%)	0
Tonsillar Hypertrophy	1/299 (0.3%)	1	0/297 (0%)	0
Asthma	0/299 (0%)	0	2/297 (0.7%)	2
Dyspnoea	0/299 (0%)	0	1/297 (0.3%)	1
Nasal Inflammation	0/299 (0%)	0	1/297 (0.3%)	1
Rhinitis Atrophic	0/299 (0%)	0	1/297 (0.3%)	1
Skin and subcutaneous tissue disorders
Rash	6/299 (2%)	6	4/297 (1.3%)	4
Dry Skin	3/299 (1%)	3	1/297 (0.3%)	1
Rash Papular	3/299 (1%)	4	1/297 (0.3%)	2
Alopecia	2/299 (0.7%)	2	3/297 (1%)	4
Erythema	2/299 (0.7%)	4	10/297 (3.4%)	10
Hyperhidrosis	2/299 (0.7%)	2	3/297 (1%)	3
Pruritus	2/299 (0.7%)	2	4/297 (1.3%)	4
Urticaria	2/299 (0.7%)	2	0/297 (0%)	0
Acne	1/299 (0.3%)	1	0/297 (0%)	0
Dermatitis Allergic	1/299 (0.3%)	1	0/297 (0%)	0
Erythema Annulare	1/299 (0.3%)	1	0/297 (0%)	0
Onychoclasis	1/299 (0.3%)	1	0/297 (0%)	0
Psoriasis	1/299 (0.3%)	1	1/297 (0.3%)	1
Rash Pruritic	1/299 (0.3%)	1	0/297 (0%)	0
Rosacea	1/299 (0.3%)	2	0/297 (0%)	0
Skin Mass	1/299 (0.3%)	1	0/297 (0%)	0
Dermatitis	0/299 (0%)	0	1/297 (0.3%)	1
Dermatitis Contact	0/299 (0%)	0	1/297 (0.3%)	1
Prurigo	0/299 (0%)	0	1/297 (0.3%)	1
Umbilical Erythema	0/299 (0%)	0	1/297 (0.3%)	1
Social circumstances
Menopause	0/299 (0%)	0	1/297 (0.3%)	1
Surgical and medical procedures
Tooth Extraction	0/299 (0%)	0	2/297 (0.7%)	2
Vascular disorders
Hypertension	11/299 (3.7%)	16	11/297 (3.7%)	12
Hypotension	2/299 (0.7%)	2	0/297 (0%)	0
Hypertensive Crisis	1/299 (0.3%)	1	1/297 (0.3%)	1
Vasculitis	1/299 (0.3%)	1	0/297 (0%)	0
Pallor	0/299 (0%)	0	1/297 (0.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

At least sixty (60) days prior to submitting or presenting a manuscript or other materials relating to the Study to a publisher, reviewer, or other outside persons, the Site shall provide to Sponsor a copy of all such manuscripts and materials, and allow Sponsor sixty (60) days to review and comment on them. If the Sponsor requests, the Site shall remove any Confidential Information (other than Study results) prior to submitting or presenting the materials.

Results Point of Contact

Name/Title	Director, Clinical Development
Organization	Samsung Bioepis
Phone	+82 31 8061 4534
Email

Responsible Party:

Samsung Bioepis Co., Ltd.

ClinicalTrials.gov Identifier:

NCT01895309

Other Study ID Numbers:

SB4-G31-RA

First Posted:

Jul 10, 2013

Last Update Posted:

Aug 17, 2017

Last Verified:

Dec 1, 2015

A Study Comparing SB4 to Enbrel® in Subjects With Moderate to Severe Rheumatoid Arthritis Despite Methotrexate Therapy

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion Criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

More Information

Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

More Information

Certain Agreements

Results Point of Contact