Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis, Adalimumab
Brief summary
This is a randomised, double-blind, parallel group, multicentre clinical study to evaluate the efficacy, safety, tolerability, pharmacokinetics and immunogenicity of SB5 compared to Humira® in subjects with moderate to severe RA despite MTX therapy.
Detailed description
Investigational product: SB5 40 mg (0.8 mL of 50 mg/mL) Indication studied: Rheumatoid arthritis
Interventions
DRUGSB5 (proposed biosimilar to adalimumab)
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
* Are male or female aged 18-75 years at the time of signing the informed consent form. * Have been diagnosed as having RA according to the revised 1987 American College of Rheumatology (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: 1. More than or equal to six swollen joints and more than or equal to six tender joints (from the 66/68 joint count system) at Screening and Randomisation. 2. Either erythrocyte sedimentation rate (Westergren) ≥ 28 mm/h or serum C-reactive protein ≥ 10 mg/dL at Screening. * Must have been treated with MTX for a total of at least 6 months prior to Randomisation and must have been on both: a stable route of administration (oral or parenteral) and stable dose of MTX (10-25 mg/week) for at least 4 weeks prior to Screening. * Female subjects who are not pregnant or nursing at Screening and Randomisation and who are not planning to become pregnant from Screening until 5 months after the last dose of IP.
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 Humira or SB5. * 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 (TB), have been recently exposed to a person with active TB, or are considered to have latent TB. * 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 a history of chronic or recurrent infection. * Have any of the following conditions: 1. History of congestive heart failure (New York Heart Association Class III/IV). 2. History of acute myocardial infarction or unstable angina within the previous 12 months prior to Screening. 3. History of demyelinating disorders. 4. History of any malignancy within the previous 5 years prior to Screening. 5. History of lymphoproliferative disease including lymphoma. 6. Any other disease or disorder which, in the opinion of the Investigator, will put the subject at risk if they are enrolled. * Have physical incapacitation (ACR functional Class IV or wheelchair-/bed-bound).
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 |
| Disease Activity Score Based on a 28 Joint Count (DAS28) | Week 24, Week 52 |
Countries
Lithuania, Poland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SB5 (Proposed Biosimilar to Adalimumab) SB5 40 mg every other week via subcutaneous injection
SB5 (proposed biosimilar to adalimumab) | 271 |
| Humira (Adalimumab) Humira 40 mg every other week via subcutaneous injection
Humira (adalimumab)
SB5 (proposed biosimilar to adalimumab) | 273 |
| Total | 544 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Randomised, Double-blind | Adverse Event | 2 | 9 | 0 | 0 |
| Randomised, Double-blind | Lack of Efficacy | 1 | 2 | 0 | 0 |
| Randomised, Double-blind | Other | 3 | 0 | 0 | 0 |
| Randomised, Double-blind | Withdrawal by Subject | 11 | 8 | 0 | 0 |
| Transition-extension | Adverse Event | 2 | 0 | 2 | 3 |
| Transition-extension | Lack of Efficacy | 0 | 0 | 1 | 1 |
| Transition-extension | Lost to Follow-up | 1 | 0 | 0 | 0 |
| Transition-extension | Other | 1 | 0 | 1 | 0 |
| Transition-extension | Withdrawal by Subject | 2 | 0 | 4 | 1 |
Baseline characteristics
| Characteristic | SB5 (Proposed Biosimilar to Adalimumab) | Humira (Adalimumab) | Total |
|---|---|---|---|
| Age, Continuous | 49.8 years STANDARD_DEVIATION 12.67 | 52.5 years STANDARD_DEVIATION 11.91 | 51.2 years STANDARD_DEVIATION 12.36 |
| Sex: Female, Male Female | 217 Participants | 224 Participants | 441 Participants |
| Sex: Female, Male Male | 54 Participants | 49 Participants | 103 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 268 | 0 / 273 |
| other Total, other adverse events | 35 / 268 | 44 / 273 |
| serious Total, serious adverse events | 9 / 268 | 16 / 273 |
Outcome results
Primary
American College of Rheumatology 20% Response Criteria (ACR20)
Time frame: Week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SB5 (Proposed Biosimilar to Adalimumab) | American College of Rheumatology 20% Response Criteria (ACR20) | 72.4 percentage of participants |
| Humira (Adalimumab) | American College of Rheumatology 20% Response Criteria (ACR20) | 72.2 percentage of participants |
Secondary
ACR20
Time frame: Week 52
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SB5 (Proposed Biosimilar to Adalimumab) | ACR20 | 76.9 percentage of participants |
| Humira (Adalimumab) | ACR20 | 81.1 percentage of participants |
| Humira (Adalimumab), Continue as Humira | ACR20 | 71.2 percentage of participants |
Secondary
American College of Rheumatology 50% Response Criteria (ACR50)
Time frame: Week 24, Week 52
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SB5 (Proposed Biosimilar to Adalimumab) | American College of Rheumatology 50% Response Criteria (ACR50) | 38.1 percentage of participants |
| Humira (Adalimumab) | American College of Rheumatology 50% Response Criteria (ACR50) | 39.7 percentage of participants |
| Humira (Adalimumab), Continue as Humira | American College of Rheumatology 50% Response Criteria (ACR50) | 49.1 percentage of participants |
| Humira (Adalimumab), Switch to SB5 at Week 52 | American College of Rheumatology 50% Response Criteria (ACR50) | 53.8 percentage of participants |
| Humira (Adalimumab), Continue as Humira at Week 52 | American College of Rheumatology 50% Response Criteria (ACR50) | 51.4 percentage of participants |
Secondary
Disease Activity Score Based on a 28 Joint Count (DAS28)
Time frame: Week 24, Week 52