Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis, Infliximab, Biosimilar
Brief summary
This is a randomized, double-blind, parallel group, multicentre clinical study to evaluate the efficacy, safety, pharmacokinetics and immunogenicity of SB2 compared to Remicade in subjects with moderate to severe Rheumatoid Arthritis (RA) despite Methotrexate (MTX) therapy.
Interventions
DRUGSB2 (proposed biosimilar to infliximab)
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 * 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 6 months after the last dose of investigational product Inclusion Criteria for Transition-Extension Period: * Have been enrolled and completed the scheduled Week 54 visit of the randomised, double-blind period of the SB2-G31-RA study * In the opinion of the Investigator, subjects who may benefit from continuing IP treatment (either SB2 or Remicade), understand the implications of taking part in the study and willing to participate in the transition-extension period
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 Remicade or SB2 * 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 30 |
Secondary
| Measure | Time frame |
|---|---|
| ACR20 | Week 54, Week 78 |
| American College of Rheumatology 50% Response Criteria (ACR50) | Week 30, Week 54, Week 78 |
| Disease Activity Score Based on a 28 Joint Count (DAS28) | Week 30, Week 54, Week 78 |
Countries
Bulgaria, Lithuania
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SB2 (Proposed Biosimilar to Inflixmab) SB2 3 mg/kg at week 0, 2, 6 then every 8 weeks thereafter via intravenous infusion up to Week 70
SB2 (proposed biosimilar to infliximab) | 291 |
| Remicade (Infliximab) Remicade 3 mg/kg at week 0, 2, 6 then every 8 weeks thereafter via intravenous infusion up to Week 46
At Week 54, subjects were randomised again in a 1:1 ratio to either continue on Remicade (Remicade/Remicade) or be transitioned to SB2 (Remicade/SB2) up to Week 70. | 293 |
| Total | 584 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Randomised, Double-blind | Adverse Event | 27 | 21 | 0 | 0 |
| Randomised, Double-blind | Lack of Efficacy | 5 | 6 | 0 | 0 |
| Randomised, Double-blind | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Randomised, Double-blind | Physician Decision | 4 | 4 | 0 | 0 |
| Randomised, Double-blind | Pregnancy | 0 | 1 | 0 | 0 |
| Randomised, Double-blind | Protocol Violation | 1 | 5 | 0 | 0 |
| Randomised, Double-blind | Subjects from Eastern Ukraine sites | 4 | 4 | 0 | 0 |
| Randomised, Double-blind | Withdrawal by Subject | 23 | 26 | 0 | 0 |
| Transition-extension | Adverse Event | 3 | 0 | 3 | 1 |
| Transition-extension | Lost to Follow-up | 3 | 0 | 1 | 2 |
| Transition-extension | Physician Decision | 2 | 0 | 0 | 1 |
| Transition-extension | Withdrawal by Subject | 7 | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | SB2 (Proposed Biosimilar to Inflixmab) | Remicade (Infliximab) | Total |
|---|---|---|---|
| Age, Continuous | 51.6 years STANDARD_DEVIATION 11.92 | 52.6 years STANDARD_DEVIATION 11.74 | 52.1 years STANDARD_DEVIATION 11.83 |
| Sex: Female, Male Female | 232 Participants | 236 Participants | 468 Participants |
| Sex: Female, Male Male | 59 Participants | 57 Participants | 116 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 290 | 1 / 293 |
| other Total, other adverse events | 201 / 290 | 203 / 293 |
| serious Total, serious adverse events | 36 / 290 | 38 / 293 |
Outcome results
Primary
American College of Rheumatology 20% Response Criteria (ACR20)
Time frame: Week 30
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SB2 (Proposed Biosimilar to Inflixmab) | American College of Rheumatology 20% Response Criteria (ACR20) | 64.1 percentage of participants |
| Remicade (Infliximab) | American College of Rheumatology 20% Response Criteria (ACR20) | 66.0 percentage of participants |
Secondary
ACR20
Time frame: Week 54, Week 78
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SB2 (Proposed Biosimilar to Inflixmab) | ACR20 | 65.3 percentage of participants |
| Remicade (Infliximab) | ACR20 | 69.2 percentage of participants |
| SB2 at Week 78 | ACR20 | 68.3 percentage of participants |
| Remicade (Infliximab), Switch to SB2 at Week 78 | ACR20 | 63.5 percentage of participants |
| Remicade (Infliximab), Continue as Remicade | ACR20 | 68.8 percentage of participants |
Secondary
American College of Rheumatology 50% Response Criteria (ACR50)
Time frame: Week 30, Week 54, Week 78
Secondary
Disease Activity Score Based on a 28 Joint Count (DAS28)
Time frame: Week 30, Week 54, Week 78