Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis, Etanercept, Biosimilar
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.
Interventions
DRUGSB4 (proposed biosimilar to etanercept)
Sponsors
Samsung Bioepis Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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 1. Other inflammatory or rheumatic diseases. 2. History of any malignancy within the previous 5 years prior to Screening 3. History of lymphoproliferative disease including lymphoma. 4. History of congestive heart failure 5. Physical incapacitation (ACR functional Class IV or wheelchair-/bed-bound). 6. History of demyelinating disorders.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| American College of Rheumatology 20% Response Criteria (ACR20) | Week 24 |
Secondary
| Measure | Time frame |
|---|---|
| ACR20 | Week 52 |
| American College of Rheumatology 50% Response Criteria (ACR50) | Week 24, Week 52 |
Countries
Poland, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SB4 (Proposed Biosimilar to Etanercept) SB4 50 mg/week via subcutaneous injection | 299 |
| Enbrel (Etanercept) Enbrel 50 mg/week via subcutaneous injection | 297 |
| Total | 596 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 13 | 17 |
| Overall Study | Lack of Efficacy | 1 | 3 |
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | Physician Decision | 15 | 10 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 9 | 18 |
Baseline characteristics
| Characteristic | SB4 (Proposed Biosimilar to Etanercept) | Enbrel (Etanercept) | Total |
|---|---|---|---|
| Age, Continuous | 52.1 years STANDARD_DEVIATION 11.72 | 51.6 years STANDARD_DEVIATION 11.63 | 51.8 years STANDARD_DEVIATION 11.67 |
| Sex: Female, Male Female | 249 Participants | 253 Participants | 502 Participants |
| Sex: Female, Male Male | 50 Participants | 44 Participants | 94 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 175 / 299 | 179 / 297 |
| serious Total, serious adverse events | 18 / 299 | 15 / 297 |
Outcome results
Primary
American College of Rheumatology 20% Response Criteria (ACR20)
Time frame: Week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SB4 (Proposed Biosimilar to Etanercept) | American College of Rheumatology 20% Response Criteria (ACR20) | 78.1 percentage of participants |
| Enbrel (Etanercept) | American College of Rheumatology 20% Response Criteria (ACR20) | 80.5 percentage of participants |
Secondary
ACR20
Time frame: Week 52
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SB4 (Proposed Biosimilar to Etanercept) | ACR20 | 80.8 percentage of participants |
| Enbrel (Etanercept) | ACR20 | 81.5 percentage of participants |
Secondary
American College of Rheumatology 50% Response Criteria (ACR50)
Time frame: Week 24, Week 52
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SB4 (Proposed Biosimilar to Etanercept) | American College of Rheumatology 50% Response Criteria (ACR50) | 46.2 percentage of participants |
| Enbrel (Etanercept) | American College of Rheumatology 50% Response Criteria (ACR50) | 42.4 percentage of participants |
| SB4 (Proposed Biosimilar to Etanercept) at Week 52 | American College of Rheumatology 50% Response Criteria (ACR50) | 58.5 percentage of participants |
| Enbrel (Etanercept) at Week 52 | American College of Rheumatology 50% Response Criteria (ACR50) | 53.2 percentage of participants |