A Study Comparing SB4 to Enbrel® in Subjects with Moderate to Severe Rheumatoid Arthritis despite Methotrexate Therapy

• Register: EUCTR
• Last refreshed on: 4 August 2015
• Main ID: EUCTR2012-005026-30-PL
• Date of registration: 08/03/2013
• Prospective Registration: Yes
• Primary sponsor: Samsung Bioepis Co., Ltd.
• Public title: A Study Comparing SB4 to Enbrel® in Subjects with Moderate to Severe Rheumatoid Arthritis despite Methotrexate Therapy
• Scientific 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
• Date of first enrolment: 17/05/2013
• Target sample size: 596
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-005026-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: Open label Extension period added as Protocol Amendment 3.1 If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Bulgaria, Colombia, Czech Republic, Hungary, India, Korea, Republic of, Lithuania, Mexico, Poland, Ukraine, United Kingdom

Contacts

• Name: Quintiles Contact Centre
• Affiliation: Quintiles Limited

• Name: Quintiles Contact Centre
• Affiliation: Quintiles Limited

Key inclusion & exclusion criteria

Inclusion criteria:
1. Are male or female aged 18–75 years at the time of signing the consent form.
2. Have been diagnosed as having RA according to the revised 1987 American College of Rheumatology (ACR) criteria
3. Have more than or equal to six swollen joints, more than or equal to six tender joints (from the 66/68 joint count system) at Screening and Randomisation and either erythrocyte sedimentation rate (Westergren) = 28 mm/h or serum C-reactive protein = 1.0 mg/dL at Screening.
4. 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 orally or parenterally for at least 4 weeks prior to Screening.
5. 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 (IP).
Subjects must meet all of the following criteria to be enrolled in the
open-label, extension period:
1. Have completed the scheduled Week 52 visit of the randomised, double-blind period of SB4-G31-RA study, may benefit from SB4 treatment at the discretion of the Investigator and are willing to
participate in the open-label, extension period.
2. Must be able to provide informed consent for the open-label, extension period, which must be obtained prior to the first administration of IP for the open-label, extension period.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 520
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 76

Exclusion criteria:
1. Have been treated previously with any biological agents including any tumour necrosis factor inhibitor.
2. Have a known hypersensitivity to human immunoglobulin proteins or other components of Enbrel or SB4.
3. Have a positive serological test for hepatitis B or hepatitis C or have a known history of infection with human immunodeficiency virus.
4. Have a current diagnosis of active tuberculosis
5. 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.
6. Have any of the following conditions
a. Other inflammatory or rheumatic diseases.
b. History of any malignancy within the previous 5 years prior to Screening
c. History of lymphoproliferative disease including lymphoma.
d. History of congestive heart failure
e. Physical incapacitation (ACR functional Class IV or wheelchair-/bed-bound).
f History of demyelinating disorders.
Subjects meeting any of the following criteria must not be enrolled in the
open-label, extension period:
1. Have been withdrawn from SB4-G31-RA Study for any reason.
2. Have had any significant medical conditions, such as an occurrence of a serious adverse event (SAE) or intolerance of SB4 or Enbrel during the 52 weeks of randomised, double-blind period which may render the subjects undesirable to participate in the study at the discretion of the Investigator.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Subjects with Moderate to Severe Rheumatoid Arthritis despite Methotrexate Therapy. The intended use of SB4 is Rheumatoid Arthritis (RA), Juvenile Idiopathic Arthritis (JIA), Psoriatic Arthritis (PsA), Ankylosing Spondylitis (AS), plaque Psoriasis (PsO) and paediatric plaque PsO.
MedDRA version: 17.1 Level: SOC Classification code 10021428 Term: Immune system disorders System Organ Class: 10021428 - Immune system disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: SB4 (etanercept biosimilar)
Product Code: SB4
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: ETANERCEPT
CAS Number: 185243-69-0
Current Sponsor code: SB4
Other descriptive name: TNFR:Fc
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-

Trade Name: Enbrel®
Product Name: Enbrel®
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: ETANERCEPT
CAS Number: 185243-69-0
Other descriptive name: TNFR:Fc
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Secondary Objective: The secondary objectives are:
? To evaluate efficacy of SB4 compared to Enbrel using relevant efficacy endpoints other than ACR 20 at Week 24 in subjects with moderate to severe RA despite MTX therapy
? To evaluate safety and tolerability of SB4 compared to Enbrel in subjects with moderate to severe RA despite MTX therapy
? To evaluate pharmacokinetics of SB4 compared to Enbrel in subjects with moderate to severe RA despite MTX therapy
? To evaluate immunogenicity of SB4 compared to Enbrel in subjects with moderate to severe RA despite MTX therapy
The secondary objectives for the open-label, extension period are:
• To evaluate long-term safety and tolerability of SB4 in subjects with RA treated previously with SB4 or Enbrel
• To evaluate long-term immunogenicity of SB4 in subjects with RA treated previously with SB4 or Enbrel
• To evaluate long-term efficacy of SB4 in subjects with RA treated previously with SB4 or Enbrel

Main Objective: The primary objective of this study is to demonstrate the equivalence of SB4 to Enbrel® at Week 24, in terms of American College of Rheumatology 20% response criteria (ACR 20) response rate in subjects with moderate to severe rheumatoid arthritis (RA) despite methotrexate (MTX) therapy.

Timepoint(s) of evaluation of this end point: Week 24

Primary end point(s): The primary endpoint for the study is the ACR 20 response at Week 24

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: ? The ACR 20 response at Week 52
? The ACR 50 response and ACR 70 response at Week 24 and Week 52
? The numeric index of the ACR response (ACR-N) at Week 24 and Week 52
? The area under the curve (AUC) of ACR-N up to Week 24
? The disease activity score based on a 28 joint count (DAS28 score) at Week 24 and Week 52
? The European League Against Rheumatism response at Week 24 and Week 52
? The AUC of the change in DAS28 from Baseline up to Week 24? Major clinical response (ACR 70 response for 6 consecutive months) at Week 52
? Change from baseline in modified Total Sharp Score at Week 52

Secondary end point(s): The secondary efficacy endpoints are:
? The ACR 20 response at Week 52
? The ACR 50 response and ACR 70 response at Week 24 and Week 52
? The numeric index of the ACR response (ACR-N) at Week 24 and Week 52
? The area under the curve (AUC) of ACR-N up to Week 24
? The disease activity score based on a 28 joint count (DAS28 score) at Week 24 and Week 52
? The European League Against Rheumatism response at Week 24 and Week 52
? The AUC of the change in DAS28 from Baseline up to Week 24? Major clinical response (ACR 70 response for 6 consecutive months) at Week 52
? Change from baseline in modified Total Sharp Score at Week 52
The secondary endpoints for the open-label, extension period:
• The ACR20, ACR50 and ACR70 response at Week 76 andWeek 100
• The ACR-N at Week 76 and Week 100
• The change in DAS28 score from Week 0 at Week 76 andWeek 100
• The EULAR response at Week 76 and Week 100
• The change from Week 0 in mTSS at Week 100

Secondary ID(s)

2012-005026-30-HU

SB4-G31-RA

Source(s) of Monetary Support

Samsung Bioepis Co., Ltd.