Rheumatoid Arthritis
Conditions
Keywords
MSB11456, RoActemra®
Brief summary
The purpose of the study is to compare the efficacy, safety and immunogenicity of MSB11456 and EU approved RoActemra® in participants with moderately to severely active rheumatoid arthritis. Participants will be randomized at the beginning of the Core Treatment Period (Baseline to Week 24) to receive either MSB11456 or EU approved RoActemra® once a week (QW). At the beginning of the Extended Treatment Period (Week 24 to Week 52), participants who received RoActemra® will be re-randomized to either continue receiving RoActemra® QW or switch to receive MSB11456 QW.
Interventions
DRUGMSB11456
Participants will receive MSB11456 subcutaneously, once a week.
Participants will receive EU-approved RoActemra® subcutaneously, once a week.
Sponsors
Fresenius Kabi SwissBioSim GmbH
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Are ≥18 years of age. * Diagnosis of rheumatoid arthritis according to the revised 1987 ACR/European League Against Rheumatism (EULAR) Classification 2010 criteria with disease duration of ≥6 months. * Have moderately to severely active rheumatoid arthritis. * Must have been treated with methotrexate for at least 12 consecutive weeks immediately prior to randomization and are on a stable dose between 10 and 25 mg/week methotrexate for the last 8 weeks prior to screening. * Have had previous inadequate clinical response to at least one modifying anti-rheumatic drug. * Women of childbearing potential (i.e., considered fertile following menarche and until becoming postmenopausal unless permanently sterile) can participate only if they have a negative serum pregnancy test at screening and a negative urine pregnancy test at Day -1 before randomization. Women of childbearing potential must have used and agree to use a highly effective contraception (i.e., methods with a failure rate of less than 1% per year), for 4 weeks before randomization and must agree to continue to practice adequate contraception for 3 months after the last study drug administration. * Must voluntarily give written informed consent before any study-related activities are performed. Participants must read and fully understand the Informed Consent Form and the requirements of the study. Participants must be willing to comply with all study visits and assessments. Participants must be willing to complete each study procedure. Note: A separate Informed Consent Form (containing important information about COVID 19, clinical research study participation and participant consent) will be provided to and signed by each participant to provide information on the general risks of study participation related to COVID-19 and to document that it is understood by the participant. Another separate Informed Consent Form will be required to be understood and signed by partners of male participating patients who become pregnant during the study or within 10 weeks after the participating patient's last dose of study drug.
Exclusion criteria
* American College of Rheumatology functional class IV as defined by the ACR classification of functional status or wheelchair/bedbound. * Previously received tocilizumab, an investigational or licensed biosimilar of tocilizumab or any interleukin-6 acting drugs. * Prior use of targeted synthetic disease-modifying anti-rheumatic drugs like janus kinase inhibitors. * Prior use of more than 2 biologic treatments for rheumatoid arthritis. * Received a live or attenuated vaccine within 4 weeks prior to randomization. * Participant is considered by the Investigator, for any reason, to be an unsuitable candidate for the study. Investigator should specifically evaluate the participant's eligibility taking into consideration COVID-19 risk factors and situation. * Has a serious and/or unstable and/or poorly controlled medical condition such as but not limited to poorly controlled diabetes, unstable ischemic heart disease, uncontrolled hypertension or other cardiovascular, cerebrovascular, cardiovascular, gastrointestinal disease, hepatic, renal, hematological, endocrine, nervous system or pulmonary disease or other relevant medical condition or a history of clinically significant disease or any other condition that, in the opinion of the Investigator, would put the participant at risk by participation in the study. * Confirmed or, based on the signs and symptoms observed at the time of assessment, suspected active COVID-19 infection at the time of screening and/or randomization. * Has had any infection as follows: 1. Herpes zoster or any opportunistic invasive infection within 6 months of screening. 2. Frequent, chronic or recurrent infections. 3. A positive test for human immunodeficiency virus subtype 1 (HIV-1) or 2 (HIV-2), hepatitis C antibody, hepatitis B surface antigen and/or core antibody for immunoglobulin G and/or immunoglobulin M or total immunoglobulin at screening. 4. A serious infection within 8 weeks prior to randomization. 5. Required treatment with oral antibiotics and/or anti-fungal drugs within 14 days prior to randomization. * Medical evidence of active or latent tuberculosis as indicated by a positive QuantiFERON®-TB Gold Plus test, chest X-ray and/or clinical examination or has had active or latent tuberculosis disease at any time in the past. * Received a COVID 19 vaccine within 4 weeks prior to randomization, are receiving ongoing COVID-19 vaccination at the time of screening or plan to receive COVID-19 vaccination before the completion of the Week 30 visit of the study. COVID-19 vaccination is considered ongoing if a multidose regimen has been started but has not been completed.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Baseline; Week 24 | The DAS28-ESR is a measure of disease activity in 28 joints that consists of a composite numerical score of the following variables: Tender Joint Count (TJC), Swollen Joint Count (SJC), erythrocyte sedimentation rate (ESR) and Patient's Global Assessment of Disease Activity. The DAS28-ESR score was derived using the formula: DAS28-ESR = 0.56\*√(TJC28) + 0.28\*√(SJC28) + 0.014\*GH + 0.70\*Ln(ESR), where, TJC28 = 28 joint count for tenderness, SJC28 = 28 joint count for swelling, Ln(ESR) = natural logarithm of ESR, GH = the general health component of the DAS (i.e., Patient's Global Assessment of Disease Activity on a scale of 1 to 100 where 100 is maximal activity). Higher values mean a higher disease activity. The level of disease activity can be interpreted as: * Remission (score of \<2.6). * Low (score of ≤2.6 to \<3.2). * Moderate (score of ≤3.2 to ≤5.1). * High (score of \>5.1) A negative change from baseline indicates an improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With 20% Improvement in American College of Rheumatology (ACR20) Response | Baseline; Week 24 | ACR20 was defined as the number of participants with at least 20% improvement from baseline in number of tender and swollen joints (68/66 joint count), and at least 20% improvement from baseline in three or more of the 5 ACR Core Set measures: * Patient's Assessment of Arthritis Pain * Physical Function Assessment (Health Assessment Questionnaire-Disability Index) * Acute phase reactant level (erythrocyte sedimentation rate or C-reactive protein) * Patient's Global Assessment of Disease Activity and * Physician's Global Assessment of Disease Activity |
| Number of Participants Who Experienced One or More Treatment-Emergent Adverse Event (TEAE) | Baseline to end of study, up to Week 63 | — |
| Number of Participants Who Experienced One or More Treatment-Emergent Serious Adverse Event (TESAE) | Baseline to end of study, up to Week 63 | — |
| Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16; Extended Period Baseline (Week 24), Week 30, Week 42, and Week 52 | The DAS28-ESR is a measure of disease activity in 28 joints that consists of a composite numerical score of the following variables: TJC, SJC, ESR and Patient's Global Assessment of Disease Activity. The DAS28-ESR score was derived using the formula: DAS28-ESR = 0.56\*√(TJC28) + 0.28\*√(SJC28) + 0.014\*GH + 0.70\*Ln(ESR), where, TJC28 = 28 joint count for tenderness, SJC28 = 28 joint count for swelling, Ln(ESR) = natural logarithm of ESR, GH = the general health component of the DAS (i.e., Patient's Global Assessment of Disease Activity on a scale of 1 to 100 where 100 is maximal activity). Higher values mean a higher disease activity. The level of disease activity can be interpreted as: * Remission (score of \<2.6). * Low (score of ≤2.6 to \<3.2). * Moderate (score of ≤3.2 to ≤5.1). * High (score of \>5.1) A negative change from baseline indicates an improvement. For weeks 30, 42 and 52, the extended baseline (week 24) was used for the change in DAS28-ESR calculation. |
| Anti-Drug Antibodies (ADAs) Titer Levels | Baseline, Week 2, Week 12, Week 24, Week 30, Week 52 and Week 55 | — |
| Percentage of Participants With Neutralizing Antibodies (NAb) | Baseline, Week 2, Week 12, Week 24, Week 30, Week 52 and Week 55 | — |
| Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) | Baseline, Week 2, Week 12, Week 24, Week 30, Week 52 and Week 55 | — |
Countries
Bulgaria, Czechia, Georgia, Hungary, Moldova, Poland, Russia, Serbia, Slovakia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Core Treatment Period: MSB11456 Participants received MSB11456 subcutaneously, once a week during the core treatment period (Baseline to Week 24). | 302 |
| Core Treatment Period: RoActemra® Participants received EU-approved RoActemra® subcutaneously, once a week during the core treatment period (Baseline to Week 24). | 302 |
| Total | 604 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Week 0 to Week 24 | Adverse Event | 14 | 10 | 0 | 0 | 0 |
| Week 0 to Week 24 | Death | 0 | 2 | 0 | 0 | 0 |
| Week 0 to Week 24 | Discontinued treatment prior to Week 24 | 4 | 4 | 0 | 0 | 0 |
| Week 0 to Week 24 | Subject Did Not Meet Eligibility But Was Randomized | 0 | 1 | 0 | 0 | 0 |
| Week 0 to Week 24 | Withdrawal By Sponsor's Decision | 1 | 0 | 0 | 0 | 0 |
| Week 0 to Week 24 | Withdrawal by Subject | 16 | 9 | 0 | 0 | 0 |
| Week 24 to Week 63 | Adverse Event | 0 | 0 | 13 | 8 | 6 |
| Week 24 to Week 63 | Death | 0 | 0 | 0 | 1 | 1 |
| Week 24 to Week 63 | Lost to Follow-up | 0 | 0 | 1 | 1 | 1 |
| Week 24 to Week 63 | Miscellaneous | 0 | 0 | 3 | 2 | 1 |
| Week 24 to Week 63 | Withdrawal by Subject | 0 | 0 | 6 | 4 | 6 |
Baseline characteristics
| Characteristic | Core Treatment Period: MSB11456 | Total | Core Treatment Period: RoActemra® |
|---|---|---|---|
| Age, Continuous | 51.2 years STANDARD_DEVIATION 12.72 | 52.2 years STANDARD_DEVIATION 12.08 | 53.2 years STANDARD_DEVIATION 11.33 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 300 Participants | 600 Participants | 300 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 302 Participants | 604 Participants | 302 Participants |
| Region of Enrollment Bulgaria | 18 participants | 34 participants | 16 participants |
| Region of Enrollment Czechia | 19 participants | 44 participants | 25 participants |
| Region of Enrollment Georgia | 43 participants | 94 participants | 51 participants |
| Region of Enrollment Hungary | 19 participants | 42 participants | 23 participants |
| Region of Enrollment Moldova | 14 participants | 23 participants | 9 participants |
| Region of Enrollment Poland | 156 participants | 303 participants | 147 participants |
| Region of Enrollment Russia | 21 participants | 40 participants | 19 participants |
| Region of Enrollment Serbia | 7 participants | 18 participants | 11 participants |
| Region of Enrollment Slovakia | 5 participants | 6 participants | 1 participants |
| Sex: Female, Male Female | 250 Participants | 498 Participants | 248 Participants |
| Sex: Female, Male Male | 52 Participants | 106 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 302 | 1 / 139 | 3 / 163 |
| other Total, other adverse events | 163 / 302 | 82 / 139 | 92 / 163 |
| serious Total, serious adverse events | 51 / 302 | 20 / 139 | 33 / 163 |
Outcome results
Primary
Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR)
The DAS28-ESR is a measure of disease activity in 28 joints that consists of a composite numerical score of the following variables: Tender Joint Count (TJC), Swollen Joint Count (SJC), erythrocyte sedimentation rate (ESR) and Patient's Global Assessment of Disease Activity. The DAS28-ESR score was derived using the formula: DAS28-ESR = 0.56\*√(TJC28) + 0.28\*√(SJC28) + 0.014\*GH + 0.70\*Ln(ESR), where, TJC28 = 28 joint count for tenderness, SJC28 = 28 joint count for swelling, Ln(ESR) = natural logarithm of ESR, GH = the general health component of the DAS (i.e., Patient's Global Assessment of Disease Activity on a scale of 1 to 100 where 100 is maximal activity). Higher values mean a higher disease activity. The level of disease activity can be interpreted as: * Remission (score of \<2.6). * Low (score of ≤2.6 to \<3.2). * Moderate (score of ≤3.2 to ≤5.1). * High (score of \>5.1) A negative change from baseline indicates an improvement.
Time frame: Baseline; Week 24
Population: ITT Analysis Set: includes all randomized participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Core Treatment Period: MSB11456 | Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | -3.53 score on a scale | Standard Error 0.106 |
| Core Treatment Period: RoActemra® | Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | -3.54 score on a scale | Standard Error 0.106 |
90% CI: [-0.16, 0.18]
Secondary
Anti-Drug Antibodies (ADAs) Titer Levels
Time frame: Baseline, Week 2, Week 12, Week 24, Week 30, Week 52 and Week 55
Population: All participants who received at least one dose of study drug (MBS11456 or EU-approved RoActemra) in either the Core Treatment Period or the Extended Treatment Period and had a valid ADA result at the specific time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Core Treatment Period: MSB11456 | Anti-Drug Antibodies (ADAs) Titer Levels | Baseline | 71.4 titer |
| Core Treatment Period: MSB11456 | Anti-Drug Antibodies (ADAs) Titer Levels | Overall (includes all time points except Baseline) | 106.3 titer |
| Core Treatment Period: MSB11456 | Anti-Drug Antibodies (ADAs) Titer Levels | Week 2 | 81.2 titer |
| Core Treatment Period: MSB11456 | Anti-Drug Antibodies (ADAs) Titer Levels | Week 24 (Extended Treatment Period Baseline) | 138.4 titer |
| Core Treatment Period: MSB11456 | Anti-Drug Antibodies (ADAs) Titer Levels | Week 12 | 113.8 titer |
| Core Treatment Period: RoActemra® | Anti-Drug Antibodies (ADAs) Titer Levels | Week 24 (Extended Treatment Period Baseline) | 102.9 titer |
| Core Treatment Period: RoActemra® | Anti-Drug Antibodies (ADAs) Titer Levels | Overall (includes all time points except Baseline) | 104.0 titer |
| Core Treatment Period: RoActemra® | Anti-Drug Antibodies (ADAs) Titer Levels | Baseline | 130.4 titer |
| Core Treatment Period: RoActemra® | Anti-Drug Antibodies (ADAs) Titer Levels | Week 2 | 88.1 titer |
| Core Treatment Period: RoActemra® | Anti-Drug Antibodies (ADAs) Titer Levels | Week 12 | 123.1 titer |
| Core Treatment Period: MSB11456; Extended Treatment Period: MSB11456 | Anti-Drug Antibodies (ADAs) Titer Levels | Week 24 (Extended Treatment Period Baseline) | 127.7 titer |
| Core Treatment Period: MSB11456; Extended Treatment Period: MSB11456 | Anti-Drug Antibodies (ADAs) Titer Levels | Week 30 | 173.0 titer |
| Core Treatment Period: MSB11456; Extended Treatment Period: MSB11456 | Anti-Drug Antibodies (ADAs) Titer Levels | Week 55 | 251.2 titer |
| Core Treatment Period: MSB11456; Extended Treatment Period: MSB11456 | Anti-Drug Antibodies (ADAs) Titer Levels | Overall (includes all time points except Baseline) | 215.4 titer |
| Core Treatment Period: MSB11456; Extended Treatment Period: MSB11456 | Anti-Drug Antibodies (ADAs) Titer Levels | Week 52 | 230.9 titer |
| Core Treatment Period: RoActemra®; Extended Treatment Period: MSB11456 | Anti-Drug Antibodies (ADAs) Titer Levels | Overall (includes all time points except Baseline) | 166.3 titer |
| Core Treatment Period: RoActemra®; Extended Treatment Period: MSB11456 | Anti-Drug Antibodies (ADAs) Titer Levels | Week 55 | 200.8 titer |
| Core Treatment Period: RoActemra®; Extended Treatment Period: MSB11456 | Anti-Drug Antibodies (ADAs) Titer Levels | Week 24 (Extended Treatment Period Baseline) | 106.1 titer |
| Core Treatment Period: RoActemra®; Extended Treatment Period: MSB11456 | Anti-Drug Antibodies (ADAs) Titer Levels | Week 52 | 174.7 titer |
| Core Treatment Period: RoActemra®; Extended Treatment Period: MSB11456 | Anti-Drug Antibodies (ADAs) Titer Levels | Week 30 | 130.6 titer |
| Core Treatment Period: EU-approved RoActemra®; Extended Treatment Period: EU-approved RoActemra® | Anti-Drug Antibodies (ADAs) Titer Levels | Overall (includes all time points except Baseline) | 101.1 titer |
| Core Treatment Period: EU-approved RoActemra®; Extended Treatment Period: EU-approved RoActemra® | Anti-Drug Antibodies (ADAs) Titer Levels | Week 24 (Extended Treatment Period Baseline) | 95.6 titer |
| Core Treatment Period: EU-approved RoActemra®; Extended Treatment Period: EU-approved RoActemra® | Anti-Drug Antibodies (ADAs) Titer Levels | Week 30 | 93.7 titer |
| Core Treatment Period: EU-approved RoActemra®; Extended Treatment Period: EU-approved RoActemra® | Anti-Drug Antibodies (ADAs) Titer Levels | Week 52 | 96.7 titer |
| Core Treatment Period: EU-approved RoActemra®; Extended Treatment Period: EU-approved RoActemra® | Anti-Drug Antibodies (ADAs) Titer Levels | Week 55 | 112.4 titer |
Secondary
Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR)
The DAS28-ESR is a measure of disease activity in 28 joints that consists of a composite numerical score of the following variables: TJC, SJC, ESR and Patient's Global Assessment of Disease Activity. The DAS28-ESR score was derived using the formula: DAS28-ESR = 0.56\*√(TJC28) + 0.28\*√(SJC28) + 0.014\*GH + 0.70\*Ln(ESR), where, TJC28 = 28 joint count for tenderness, SJC28 = 28 joint count for swelling, Ln(ESR) = natural logarithm of ESR, GH = the general health component of the DAS (i.e., Patient's Global Assessment of Disease Activity on a scale of 1 to 100 where 100 is maximal activity). Higher values mean a higher disease activity. The level of disease activity can be interpreted as: * Remission (score of \<2.6). * Low (score of ≤2.6 to \<3.2). * Moderate (score of ≤3.2 to ≤5.1). * High (score of \>5.1) A negative change from baseline indicates an improvement. For weeks 30, 42 and 52, the extended baseline (week 24) was used for the change in DAS28-ESR calculation.
Time frame: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16; Extended Period Baseline (Week 24), Week 30, Week 42, and Week 52
Population: ITT Analysis Set: includes all randomized participants in either the Core Treatment period or the Extended Treatment period and who had a result at baseline and at each specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Core Treatment Period: MSB11456 | Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Week 8 | -2.75 score on a scale | Standard Deviation 1.22 |
| Core Treatment Period: MSB11456 | Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Week 4 | -1.96 score on a scale | Standard Deviation 1.184 |
| Core Treatment Period: MSB11456 | Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Week 2 | -1.24 score on a scale | Standard Deviation 1.022 |
| Core Treatment Period: MSB11456 | Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Week 16 | -3.41 score on a scale | Standard Deviation 1.288 |
| Core Treatment Period: MSB11456 | Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Week 12 | -3.13 score on a scale | Standard Deviation 1.249 |
| Core Treatment Period: RoActemra® | Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Week 16 | -3.32 score on a scale | Standard Deviation 1.242 |
| Core Treatment Period: RoActemra® | Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Week 2 | -1.21 score on a scale | Standard Deviation 0.949 |
| Core Treatment Period: RoActemra® | Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Week 4 | -1.98 score on a scale | Standard Deviation 1.135 |
| Core Treatment Period: RoActemra® | Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Week 8 | -2.69 score on a scale | Standard Deviation 1.26 |
| Core Treatment Period: RoActemra® | Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Week 12 | -3.09 score on a scale | Standard Deviation 1.279 |
| Core Treatment Period: MSB11456; Extended Treatment Period: MSB11456 | Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Week 42 | -0.34 score on a scale | Standard Deviation 1.042 |
| Core Treatment Period: MSB11456; Extended Treatment Period: MSB11456 | Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Week 30 | -0.16 score on a scale | Standard Deviation 0.801 |
| Core Treatment Period: MSB11456; Extended Treatment Period: MSB11456 | Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Week 52 | -0.42 score on a scale | Standard Deviation 1.185 |
| Core Treatment Period: RoActemra®; Extended Treatment Period: MSB11456 | Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Week 42 | -0.08 score on a scale | Standard Deviation 1.026 |
| Core Treatment Period: RoActemra®; Extended Treatment Period: MSB11456 | Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Week 30 | -0.13 score on a scale | Standard Deviation 0.756 |
| Core Treatment Period: RoActemra®; Extended Treatment Period: MSB11456 | Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Week 52 | -0.31 score on a scale | Standard Deviation 1.064 |
| Core Treatment Period: EU-approved RoActemra®; Extended Treatment Period: EU-approved RoActemra® | Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Week 30 | -0.02 score on a scale | Standard Deviation 0.863 |
| Core Treatment Period: EU-approved RoActemra®; Extended Treatment Period: EU-approved RoActemra® | Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Week 52 | -0.37 score on a scale | Standard Deviation 1.086 |
| Core Treatment Period: EU-approved RoActemra®; Extended Treatment Period: EU-approved RoActemra® | Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) | Week 42 | -0.27 score on a scale | Standard Deviation 1.031 |
Secondary
Number of Participants Who Experienced One or More Treatment-Emergent Adverse Event (TEAE)
Time frame: Baseline to end of study, up to Week 63
Population: Safety Analysis Set: all participants who received at least one dose of study drug (MBS11456 or EU-approved RoActemra).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Core Treatment Period: MSB11456 | Number of Participants Who Experienced One or More Treatment-Emergent Adverse Event (TEAE) | 237 Participants |
| Core Treatment Period: RoActemra® | Number of Participants Who Experienced One or More Treatment-Emergent Adverse Event (TEAE) | 105 Participants |
| Core Treatment Period: MSB11456; Extended Treatment Period: MSB11456 | Number of Participants Who Experienced One or More Treatment-Emergent Adverse Event (TEAE) | 125 Participants |
Secondary
Number of Participants Who Experienced One or More Treatment-Emergent Serious Adverse Event (TESAE)
Time frame: Baseline to end of study, up to Week 63
Population: Safety Analysis Set: all participants who received at least one dose of study drug (MBS11456 or EU-approved RoActemra).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Core Treatment Period: MSB11456 | Number of Participants Who Experienced One or More Treatment-Emergent Serious Adverse Event (TESAE) | 51 Participants |
| Core Treatment Period: RoActemra® | Number of Participants Who Experienced One or More Treatment-Emergent Serious Adverse Event (TESAE) | 20 Participants |
| Core Treatment Period: MSB11456; Extended Treatment Period: MSB11456 | Number of Participants Who Experienced One or More Treatment-Emergent Serious Adverse Event (TESAE) | 33 Participants |
Secondary
Number of Participants With 20% Improvement in American College of Rheumatology (ACR20) Response
ACR20 was defined as the number of participants with at least 20% improvement from baseline in number of tender and swollen joints (68/66 joint count), and at least 20% improvement from baseline in three or more of the 5 ACR Core Set measures: * Patient's Assessment of Arthritis Pain * Physical Function Assessment (Health Assessment Questionnaire-Disability Index) * Acute phase reactant level (erythrocyte sedimentation rate or C-reactive protein) * Patient's Global Assessment of Disease Activity and * Physician's Global Assessment of Disease Activity
Time frame: Baseline; Week 24
Population: ITT Analysis Set: includes all randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Core Treatment Period: MSB11456 | Number of Participants With 20% Improvement in American College of Rheumatology (ACR20) Response | 244 Participants |
| Core Treatment Period: RoActemra® | Number of Participants With 20% Improvement in American College of Rheumatology (ACR20) Response | 256 Participants |
95% CI: [-9.97, 2.11]
Secondary
Percentage of Participants With Neutralizing Antibodies (NAb)
Time frame: Baseline, Week 2, Week 12, Week 24, Week 30, Week 52 and Week 55
Population: All participants who received at least one dose of study drug (MBS11456 or EU-approved RoActemra) in either the Core Treatment Period or the Extended Treatment Period and had a valid ADA result at the specific time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Core Treatment Period: MSB11456 | Percentage of Participants With Neutralizing Antibodies (NAb) | Week 24 (Extended Treatment Period Baseline) | 2.9 percentage of participants |
| Core Treatment Period: MSB11456 | Percentage of Participants With Neutralizing Antibodies (NAb) | Overall (includes all time points except Baseline) | 8.4 percentage of participants |
| Core Treatment Period: MSB11456 | Percentage of Participants With Neutralizing Antibodies (NAb) | Baseline | 0 percentage of participants |
| Core Treatment Period: MSB11456 | Percentage of Participants With Neutralizing Antibodies (NAb) | Week 12 | 2.5 percentage of participants |
| Core Treatment Period: MSB11456 | Percentage of Participants With Neutralizing Antibodies (NAb) | Week 2 | 3.8 percentage of participants |
| Core Treatment Period: RoActemra® | Percentage of Participants With Neutralizing Antibodies (NAb) | Week 24 (Extended Treatment Period Baseline) | 4.9 percentage of participants |
| Core Treatment Period: RoActemra® | Percentage of Participants With Neutralizing Antibodies (NAb) | Week 12 | 4.1 percentage of participants |
| Core Treatment Period: RoActemra® | Percentage of Participants With Neutralizing Antibodies (NAb) | Overall (includes all time points except Baseline) | 11.3 percentage of participants |
| Core Treatment Period: RoActemra® | Percentage of Participants With Neutralizing Antibodies (NAb) | Week 2 | 3.4 percentage of participants |
| Core Treatment Period: RoActemra® | Percentage of Participants With Neutralizing Antibodies (NAb) | Baseline | 0 percentage of participants |
| Core Treatment Period: MSB11456; Extended Treatment Period: MSB11456 | Percentage of Participants With Neutralizing Antibodies (NAb) | Week 52 | 1.6 percentage of participants |
| Core Treatment Period: MSB11456; Extended Treatment Period: MSB11456 | Percentage of Participants With Neutralizing Antibodies (NAb) | Week 55 | 7.0 percentage of participants |
| Core Treatment Period: MSB11456; Extended Treatment Period: MSB11456 | Percentage of Participants With Neutralizing Antibodies (NAb) | Overall (includes all time points except Baseline) | 13.2 percentage of participants |
| Core Treatment Period: MSB11456; Extended Treatment Period: MSB11456 | Percentage of Participants With Neutralizing Antibodies (NAb) | Week 30 | 6.1 percentage of participants |
| Core Treatment Period: MSB11456; Extended Treatment Period: MSB11456 | Percentage of Participants With Neutralizing Antibodies (NAb) | Week 24 (Extended Treatment Period Baseline) | 3.8 percentage of participants |
| Core Treatment Period: RoActemra®; Extended Treatment Period: MSB11456 | Percentage of Participants With Neutralizing Antibodies (NAb) | Week 52 | 2.4 percentage of participants |
| Core Treatment Period: RoActemra®; Extended Treatment Period: MSB11456 | Percentage of Participants With Neutralizing Antibodies (NAb) | Week 24 (Extended Treatment Period Baseline) | 5.8 percentage of participants |
| Core Treatment Period: RoActemra®; Extended Treatment Period: MSB11456 | Percentage of Participants With Neutralizing Antibodies (NAb) | Week 30 | 9.7 percentage of participants |
| Core Treatment Period: RoActemra®; Extended Treatment Period: MSB11456 | Percentage of Participants With Neutralizing Antibodies (NAb) | Week 55 | 6.6 percentage of participants |
| Core Treatment Period: RoActemra®; Extended Treatment Period: MSB11456 | Percentage of Participants With Neutralizing Antibodies (NAb) | Overall (includes all time points except Baseline) | 16.8 percentage of participants |
| Core Treatment Period: EU-approved RoActemra®; Extended Treatment Period: EU-approved RoActemra® | Percentage of Participants With Neutralizing Antibodies (NAb) | Week 55 | 9.0 percentage of participants |
| Core Treatment Period: EU-approved RoActemra®; Extended Treatment Period: EU-approved RoActemra® | Percentage of Participants With Neutralizing Antibodies (NAb) | Overall (includes all time points except Baseline) | 11.9 percentage of participants |
| Core Treatment Period: EU-approved RoActemra®; Extended Treatment Period: EU-approved RoActemra® | Percentage of Participants With Neutralizing Antibodies (NAb) | Week 30 | 3.0 percentage of participants |
| Core Treatment Period: EU-approved RoActemra®; Extended Treatment Period: EU-approved RoActemra® | Percentage of Participants With Neutralizing Antibodies (NAb) | Week 52 | 1.6 percentage of participants |
| Core Treatment Period: EU-approved RoActemra®; Extended Treatment Period: EU-approved RoActemra® | Percentage of Participants With Neutralizing Antibodies (NAb) | Week 24 (Extended Treatment Period Baseline) | 5.9 percentage of participants |
Secondary
Percentage of Participants With Positive Anti-Drug Antibodies (ADAs)
Time frame: Baseline, Week 2, Week 12, Week 24, Week 30, Week 52 and Week 55
Population: All participants who received at least one dose of study drug (MBS11456 or EU-approved RoActemra) in either the Core Treatment Period or the Extended Treatment Period and had a valid ADA result at the specific time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Core Treatment Period: MSB11456 | Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) | Baseline | 6.6 percentage of participants |
| Core Treatment Period: MSB11456 | Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) | Overall (includes all time points expect Baseline) | 96.0 percentage of participants |
| Core Treatment Period: MSB11456 | Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) | Week 2 | 87.1 percentage of participants |
| Core Treatment Period: MSB11456 | Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) | Week 24 (Extended Treatment Period Baseline) | 76.3 percentage of participants |
| Core Treatment Period: MSB11456 | Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) | Week 12 | 79.0 percentage of participants |
| Core Treatment Period: RoActemra® | Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) | Week 24 (Extended Treatment Period Baseline) | 68.6 percentage of participants |
| Core Treatment Period: RoActemra® | Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) | Overall (includes all time points expect Baseline) | 96.3 percentage of participants |
| Core Treatment Period: RoActemra® | Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) | Baseline | 8.3 percentage of participants |
| Core Treatment Period: RoActemra® | Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) | Week 2 | 88.7 percentage of participants |
| Core Treatment Period: RoActemra® | Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) | Week 12 | 74.3 percentage of participants |
| Core Treatment Period: MSB11456; Extended Treatment Period: MSB11456 | Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) | Week 24 (Extended Treatment Period Baseline) | 86.8 percentage of participants |
| Core Treatment Period: MSB11456; Extended Treatment Period: MSB11456 | Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) | Week 30 | 76.7 percentage of participants |
| Core Treatment Period: MSB11456; Extended Treatment Period: MSB11456 | Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) | Week 55 | 81.4 percentage of participants |
| Core Treatment Period: MSB11456; Extended Treatment Period: MSB11456 | Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) | Overall (includes all time points expect Baseline) | 97.4 percentage of participants |
| Core Treatment Period: MSB11456; Extended Treatment Period: MSB11456 | Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) | Week 52 | 80.9 percentage of participants |
| Core Treatment Period: RoActemra®; Extended Treatment Period: MSB11456 | Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) | Overall (includes all time points expect Baseline) | 97.1 percentage of participants |
| Core Treatment Period: RoActemra®; Extended Treatment Period: MSB11456 | Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) | Week 55 | 82.8 percentage of participants |
| Core Treatment Period: RoActemra®; Extended Treatment Period: MSB11456 | Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) | Week 24 (Extended Treatment Period Baseline) | 77.7 percentage of participants |
| Core Treatment Period: RoActemra®; Extended Treatment Period: MSB11456 | Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) | Week 52 | 76.8 percentage of participants |
| Core Treatment Period: RoActemra®; Extended Treatment Period: MSB11456 | Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) | Week 30 | 73.1 percentage of participants |
| Core Treatment Period: EU-approved RoActemra®; Extended Treatment Period: EU-approved RoActemra® | Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) | Overall (includes all time points expect Baseline) | 94.1 percentage of participants |
| Core Treatment Period: EU-approved RoActemra®; Extended Treatment Period: EU-approved RoActemra® | Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) | Week 24 (Extended Treatment Period Baseline) | 87.5 percentage of participants |
| Core Treatment Period: EU-approved RoActemra®; Extended Treatment Period: EU-approved RoActemra® | Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) | Week 30 | 65.9 percentage of participants |
| Core Treatment Period: EU-approved RoActemra®; Extended Treatment Period: EU-approved RoActemra® | Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) | Week 52 | 61.1 percentage of participants |
| Core Treatment Period: EU-approved RoActemra®; Extended Treatment Period: EU-approved RoActemra® | Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) | Week 55 | 77.9 percentage of participants |