Rheumatoid ArthritisPhase 3NCT01895309
A Study Comparing SB4 to Enbrel® in Subjects With Moderate to Severe Rheumatoid Arthritis Despite Methotrexate Therapy
A Phase 3 study testing Enbrel (etanercept) and SB4 (proposed biosimilar to etanercept) in people with Rheumatoid Arthritis, run by Samsung Bioepis Co., Ltd. at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Enbrel (etanercept) and SB4 (proposed biosimilar to etanercept)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 596 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Jun 2013to Oct 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
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
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.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Enbrel (etanercept), SB4 (proposed biosimilar to etanercept)
- Keywords
- Rheumatoid Arthritis, Etanercept, Biosimilar
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Enbrel (etanercept)Drug
SB4 (proposed biosimilar to etanercept)Drug
| Study group | Role | What they receive |
|---|---|---|
| SB4 (proposed biosimilar to etanercept) | Experimental | SB4 50 mg/week via subcutaneous injection Receives: Drug: SB4 (proposed biosimilar to etanercept) |
| Enbrel (etanercept) | Active comparator | Enbrel 50 mg/week via subcutaneous injection Receives: Drug: Enbrel (etanercept) |
What is being measured
The primary outcome is the main question the study is designed to answer.
American College of Rheumatology 20% Response Criteria (ACR20)
Measured: Week 24
Secondary outcomes (2)
ACR20
Measured: Week 52
American College of Rheumatology 50% Response Criteria (ACR50)
Measured: Week 24, Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2013 (estimated)
- Study startJun 2013
- Primary completionApr 2014
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 596 participants (actual)
Sponsor and investigators
- Lead sponsor
- Samsung Bioepis Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jiri Vencovsky, M.D., Ph.D., Principal investigator, Charles University, Czech Republic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01895309
- Sponsor's protocol ID
- SB4-G31-RA
- Status last verified
- Dec 2015
- First submitted
- 3 Jul 2013
- Last updated
- 17 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Emery P, Suh CH, Weinblatt ME, Smolen JS, Keystone EC, Genovese M, Vencovsky J, Kay J, Hong E, Baek Y, Ghil J. Impact of immunogenicity on efficacy and tolerability of tumour necrosis factor inhibitors: pooled analysis of biosimilar studies in rheumatoid arthritis. Scand J Rheumatol. 2020 Sep;49(5):361-370. doi: 10.1080/03009742.2020.1732458. Epub 2020 May 29.
PubMed 32468892Smolen JS, Choe JY, Weinblatt ME, Emery P, Keystone E, Genovese MC, Myung G, Hong E, Baek I, Ghil J. Pooled analysis of TNF inhibitor biosimilar studies comparing radiographic progression by disease activity states in rheumatoid arthritis. RMD Open. 2020 Jan;6(1):e001096. doi: 10.1136/rmdopen-2019-001096.
PubMed 31958281Emery P, Vencovsky J, Sylwestrzak A, Leszczynski P, Porawska W, Baranauskaite A, Tseluyko V, Zhdan VM, Stasiuk B, Milasiene R, Barrera Rodriguez AA, Cheong SY, Ghil J. 52-week results of the phase 3 randomized study comparing SB4 with reference etanercept in patients with active rheumatoid arthritis. Rheumatology (Oxford). 2017 Dec 1;56(12):2093-2101. doi: 10.1093/rheumatology/kex269.
PubMed 28968793Emery P, Vencovsky J, Sylwestrzak A, Leszczynski P, Porawska W, Stasiuk B, Hilt J, Mosterova Z, Cheong SY, Ghil J. Long-term efficacy and safety in patients with rheumatoid arthritis continuing on SB4 or switching from reference etanercept to SB4. Ann Rheum Dis. 2017 Nov 13;76(12):1986-1991. doi: 10.1136/annrheumdis-2017-211591.
PubMed 28794078Emery P, Vencovsky J, Sylwestrzak A, Leszczynski P, Porawska W, Baranauskaite A, Tseluyko V, Zhdan VM, Stasiuk B, Milasiene R, Barrera Rodriguez AA, Cheong SY, Ghil J. A phase III randomised, double-blind, parallel-group study comparing SB4 with etanercept reference product in patients with active rheumatoid arthritis despite methotrexate therapy. Ann Rheum Dis. 2017 Jan;76(1):51-57. doi: 10.1136/annrheumdis-2015-207588. Epub 2015 Jul 6.
PubMed 26150601
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01895309
- Acronym / sponsor ID
- SB4-G31-RA
- Conditions
- Rheumatoid Arthritis
- Keywords
- Rheumatoid Arthritis, Etanercept, Biosimilar
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 596 participants (actual)
- Lead sponsor
- Samsung Bioepis Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- Jun 2013
- Primary completion
- Apr 2014 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 10 Jul 2013 (estimated)
- Results
- Posted 29 Aug 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SB4 (proposed biosimilar to etanercept) | Experimental | Drug: SB4 (proposed biosimilar to etanercept)SB4 50 mg/week via subcutaneous injection |
| Enbrel (etanercept) | Active comparator | Drug: Enbrel (etanercept)Enbrel 50 mg/week via subcutaneous injection |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Enbrel (etanercept) | Drug | Enbrel (etanercept) |
| SB4 (proposed biosimilar to etanercept) | Drug | SB4 (proposed biosimilar to etanercept) |
Primary outcome
American College of Rheumatology 20% Response Criteria (ACR20)
Time frame: Week 24
2 secondary outcomes
ACR20
Time frame: Week 52
American College of Rheumatology 50% Response Criteria (ACR50)
Time frame: Week 24, Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32468892Emery P, Suh CH, Weinblatt ME, Smolen JS, Keystone EC, Genovese M, Vencovsky J, Kay J, Hong E, Baek Y, Ghil J. Impact of immunogenicity on efficacy and tolerability of tumour necrosis factor inhibitors: pooled analysis of biosimilar studies in rheumatoid arthritis. Scand J Rheumatol. 2020 Sep;49(5):361-370. doi: 10.1080/03009742.2020.1732458. Epub 2020 May 29.
- Derived from this study: PubMed 31958281Smolen JS, Choe JY, Weinblatt ME, Emery P, Keystone E, Genovese MC, Myung G, Hong E, Baek I, Ghil J. Pooled analysis of TNF inhibitor biosimilar studies comparing radiographic progression by disease activity states in rheumatoid arthritis. RMD Open. 2020 Jan;6(1):e001096. doi: 10.1136/rmdopen-2019-001096.
- Derived from this study: PubMed 28968793Emery P, Vencovsky J, Sylwestrzak A, Leszczynski P, Porawska W, Baranauskaite A, Tseluyko V, Zhdan VM, Stasiuk B, Milasiene R, Barrera Rodriguez AA, Cheong SY, Ghil J. 52-week results of the phase 3 randomized study comparing SB4 with reference etanercept in patients with active rheumatoid arthritis. Rheumatology (Oxford). 2017 Dec 1;56(12):2093-2101. doi: 10.1093/rheumatology/kex269.
- Derived from this study: PubMed 28794078Emery P, Vencovsky J, Sylwestrzak A, Leszczynski P, Porawska W, Stasiuk B, Hilt J, Mosterova Z, Cheong SY, Ghil J. Long-term efficacy and safety in patients with rheumatoid arthritis continuing on SB4 or switching from reference etanercept to SB4. Ann Rheum Dis. 2017 Nov 13;76(12):1986-1991. doi: 10.1136/annrheumdis-2017-211591.
- Derived from this study: PubMed 26150601Emery P, Vencovsky J, Sylwestrzak A, Leszczynski P, Porawska W, Baranauskaite A, Tseluyko V, Zhdan VM, Stasiuk B, Milasiene R, Barrera Rodriguez AA, Cheong SY, Ghil J. A phase III randomised, double-blind, parallel-group study comparing SB4 with etanercept reference product in patients with active rheumatoid arthritis despite methotrexate therapy. Ann Rheum Dis. 2017 Jan;76(1):51-57. doi: 10.1136/annrheumdis-2015-207588. Epub 2015 Jul 6.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jiri Vencovsky, M.D., Ph.D. principal investigator
Charles University, Czech Republic
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Enbrel (etanercept) and SB4 (proposed biosimilar to etanercept) in people with Rheumatoid Arthritis, run by Samsung Bioepis Co., Ltd. at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Poland, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Aug 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
American College of Rheumatology 20% Response Criteria (ACR20) (time frame: Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01895309, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2017.