Rheumatoid Arthritis
Conditions
Brief summary
The purpose of this study is to determine the PK/PD, efficacy and safety of GP2013 in patients with severe rheumatoid arthritis.
Interventions
BIOLOGICALGP2013
1000 mg iv infusion on two separate occasions, two weeks apart (i.e. on Day 1 and on Day 15)
BIOLOGICALMabThera
1000 mg iv infusion on two separate occasions, two weeks apart (i.e. on Day 1 and on Day 15)
BIOLOGICALRituxan
1000 mg iv infusion on two separate occasions, two weeks apart (i.e. on Day 1 and on Day 15)
Sponsors
Novartis Pharmaceuticals
Sandoz
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
* Rheumatoid arthritis as defined by the 1987 ACR classification * Severe active seropositive disease * Inadequate response or intolerance to other DMARDs and anti-TNFs * Treatment with Methotrexate
Exclusion criteria
* Patients with systemic manifestations of rheumatoid arthritis * Female patients nursing * Women of childbearing potential unless using birth control * Active infection * Known immunodeficiency syndrome * Positive Hepatitis B surface antigen or antibodies to Hepatitis C * History of cancer Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC(0-inf) of GP2013, MabThera and Rituxan Following IV Infusion in Patients With RA | From baseline to 24 weeks | Area under the curve AUC(0-inf) calculated based on serum samples, collected from baseline up to 24 weeks: Day 1, 4, 8, 15, 18, 29, 57, 85,113 and 169 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Serum Concentration (Cmax) of GP2013, MabThera and Rituxan Following IV Infusion in Patients With RA | From baseline to week 24 | Maximum serum concentration (Cmax) after the first infusion of GP2013, MabThera and Rituxan in patients with RA. Samples collected from baseline up to 24 weeks: Day 1, 4, 8, 15, 18, 29, 57, 85,113 and 169. |
| Area Under the Effect Curve From Baseline to Day 14 (AUEC(0-14d)) of Percent B-cells of GP2013, MabThera and Rituxan in Patients With RA | 14 days | Area under the effect curve of percent change of peripheral B-cell count from baseline to Day 14 (AUEC(0-14d)) of GP2013, MabThera and Rituxan in patients with RA |
| Change From Baseline in DAS28(CRP) at Week 24 | 24 weeks | Change from baseline in Disease Activity Score 28 joint count - C-reactive proteine DAS28(CRP) at Week 24. In order to calculate the DAS28(CRP) the number of tender joints and swollen joints were assessed using 28-joint count (tender28 and swollen28).The patient's global assessment of disease activity (GH) measured on a Visual Analogue Scale (VAS from 0mm - best to 100mm - worst) was obtained. DAS28(CRP) = 0.56 \* sqrt(tender28) + 0.28\* sqrt(swollen28) + 0.36 \* ln(CRP+1) + 0.014 \* GH + 0.96 The DAS28(CRP) provides a number on a scale from 0 to 10 indicating the current activity of the RA, while lower values correspond with less disease activity. A decrease in DAS28 signifies a clinical improvement. |
| Summary of Disease Activity According to CDAI | At week 24 | In order to calculate the Clinical Disease Activity Index (CDAI) the number of tender and swollen joints were assessed using the 28 -joint count (tender28 and swollen28). The patient's global assessment of disease activity and the physician's global assessment of disease activity were measured using a Visual Analogue Scale (VAS) of 10 cm (from 0=best to 10=worst). CDAI = tender28 + swollen28 + patient's global assessment (in cm) + physician's global assessment (in cm) |
| Summary of Disease Activity According to SDAI | At week 24 | In order to calculate the Simplified Disease Activity Index (SDAI) the number of tender and swollen joints were assessed using the 28 -joint count (tender28 and swollen28). The patient's global assessment of disease activity and the physician's global assessment of disease activity were measured using a Visual Analogue Scale (VAS) of 10 cm (from 0=best to 10=worst). SDAI = CDAI + CRP (in mg/dL) (CDAI = tender28 + swollen28 + patient's global assessment (in cm) + physician's global assessment (in cm)) |
| Participant Response as Assessed by EULAR Response Criteria | At week 24 | Present DAS28 ≤ 3.2 (low): good response (if improvement \> 1.2), moderate response (if improvement \>0.6 and ≤ 1.2), no response (if improvement ≤ 0.6). Present DAS28 \> 3.2 to ≤ 5.1 (moderate): moderate response (if improvement \> 1.2), moderate response (if improvement \>0.6 and ≤ 1.2), no response (if improvement ≤ 0.6). Present DAS28 \> 5.1 (high): moderate response (if improvement \> 1.2), no response (if improvement \>0.6 and ≤ 1.2), no response (if improvement ≤ 0.6). |
| Number of Patients With ACR20 (CRP) Response | 24 weeks | A patient will be considered as improved according the ACR20 criteria * at least 20 % improvement from baseline in tender joint count, using the 68-joint count * at least 20 % improvement from baseline in swollen joint count, using the 66-joint count * and at least 20% improvement from baseline in a least 3 of the following 5 measures: * Patient's assessment of RA pain (VAS 100 mm) * Patient's global assessment of disease activity (VAS 100 mm) * Physician's global assessment of disease activity (VAS 100 mm) * Patient self-assessed disability (Health Assessment Questionnaire disability index) * Acute phase reactant (C-reactive protein or erythrocyte sedimentation rate) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With at Least One Anti-Drug-Antibody (ADA) Positive Serum Sample | through study completion, an average of 1 year | Number of patients with at least one post-baseline Anti-Drug-Antibody (ADA) positive serum sample until the last study visit. Sampling was at Day 1, 29, 113, 169, 267, 365, optional visit 1 (could be at any time between day 169 - week 24 and day 365 - week 52 for patients, who received a 2nd treatment course) and optional visit 2 (only applicable for patients, who received a 2nd treatment course, 26 weeks thereafter, if this was after day 365 - week 52). |
Countries
Argentina, Austria, Belgium, Brazil, Estonia, France, Germany, Hungary, India, Italy, Romania, Spain, Turkey (Türkiye), United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GP2013 GP2013: 1000 mg iv infusion on two separate occasions, two weeks apart (i.e. on Day 1 and on Day 15) | 133 |
| MabThera MabThera: 1000 mg iv infusion on two separate occasions, two weeks apart (i.e. on Day 1 and on Day 15) | 87 |
| Rituxan Rituxan: 1000 mg iv infusion on two separate occasions, two weeks apart (i.e. on Day 1 and on Day 15) | 92 |
| Total | 312 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 5 | 3 |
| Overall Study | Death | 1 | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 3 | 1 |
| Overall Study | Protocol Violation | 3 | 2 | 0 |
| Overall Study | Unsatisfactory therapeutic effect | 6 | 3 | 4 |
| Overall Study | Withdrawal by Subject | 5 | 5 | 3 |
Baseline characteristics
| Characteristic | MabThera | Total | Rituxan | GP2013 |
|---|---|---|---|---|
| Age, Continuous | 52.17 years STANDARD_DEVIATION 12.531 | 54.10 years STANDARD_DEVIATION 11.701 | 54.95 years STANDARD_DEVIATION 10.75 | 54.42 years STANDARD_DEVIATION 11.779 |
| Anti-drug antibodies (ADA) Missing | 0 Participants | 3 Participants | 2 Participants | 1 Participants |
| Anti-drug antibodies (ADA) Negative | 85 Participants | 304 Participants | 87 Participants | 132 Participants |
| Anti-drug antibodies (ADA) Positive | 2 Participants | 5 Participants | 3 Participants | 0 Participants |
| Body Mass Index (BMI) | 27.25 kg/m2 STANDARD_DEVIATION 6 | 28.02 kg/m2 STANDARD_DEVIATION 6.353 | 29.66 kg/m2 STANDARD_DEVIATION 6.606 | 27.37 kg/m2 STANDARD_DEVIATION 6.23 |
| Disease Activity Score 28 joint count - C-reactive proteine (DAS28-CRP) | 5.85 units on a scale STANDARD_DEVIATION 0.88 | 5.86 units on a scale STANDARD_DEVIATION 0.935 | 5.91 units on a scale STANDARD_DEVIATION 1.009 | 5.83 units on a scale STANDARD_DEVIATION 0.922 |
| Dose of methotrexate at baseline | 14.65 mg/week STANDARD_DEVIATION 5.154 | 15.03 mg/week STANDARD_DEVIATION 4.939 | 15.29 mg/week STANDARD_DEVIATION 4.888 | 15.09 mg/week STANDARD_DEVIATION 4.856 |
| Duration of Rheumatoid Arthritis(RA) | 10.81 years STANDARD_DEVIATION 7.137 | 10.78 years STANDARD_DEVIATION 7.874 | 11.10 years STANDARD_DEVIATION 8.299 | 10.53 years STANDARD_DEVIATION 8.074 |
| Number of patients having received 1, 2 or >2 TNF inhibitor therapies. 1 | 70 Participants | 252 Participants | 73 Participants | 109 Participants |
| Number of patients having received 1, 2 or >2 TNF inhibitor therapies. 2 | 16 Participants | 47 Participants | 13 Participants | 18 Participants |
| Number of patients having received 1, 2 or >2 TNF inhibitor therapies. >2 | 1 Participants | 13 Participants | 6 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 24 Participants | 0 Participants | 12 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 13 Participants | 6 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 13 Participants | 11 Participants | 2 Participants |
| Race (NIH/OMB) White | 68 Participants | 260 Participants | 75 Participants | 117 Participants |
| Region of Enrollment Argentina | 3 participants | 20 participants | 9 participants | 8 participants |
| Region of Enrollment Austria | 10 participants | 20 participants | 3 participants | 7 participants |
| Region of Enrollment Belgium | 4 participants | 5 participants | 0 participants | 1 participants |
| Region of Enrollment Brazil | 12 participants | 50 participants | 19 participants | 19 participants |
| Region of Enrollment Estonia | 0 participants | 2 participants | 1 participants | 1 participants |
| Region of Enrollment France | 1 participants | 5 participants | 0 participants | 4 participants |
| Region of Enrollment Germany | 17 participants | 62 participants | 14 participants | 31 participants |
| Region of Enrollment Hungary | 0 participants | 4 participants | 1 participants | 3 participants |
| Region of Enrollment India | 12 participants | 24 participants | 0 participants | 12 participants |
| Region of Enrollment Italy | 3 participants | 11 participants | 3 participants | 5 participants |
| Region of Enrollment Romania | 8 participants | 23 participants | 6 participants | 9 participants |
| Region of Enrollment Russia | 0 participants | 17 participants | 11 participants | 6 participants |
| Region of Enrollment Spain | 16 participants | 33 participants | 4 participants | 13 participants |
| Region of Enrollment Turkey | 1 participants | 7 participants | 2 participants | 4 participants |
| Region of Enrollment United States | 0 participants | 29 participants | 19 participants | 10 participants |
| Sex: Female, Male Female | 73 Participants | 262 Participants | 78 Participants | 111 Participants |
| Sex: Female, Male Male | 14 Participants | 50 Participants | 14 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 133 | 0 / 87 | 1 / 92 |
| other Total, other adverse events | 87 / 133 | 56 / 87 | 60 / 92 |
| serious Total, serious adverse events | 16 / 133 | 14 / 87 | 9 / 92 |
Outcome results
Primary
AUC(0-inf) of GP2013, MabThera and Rituxan Following IV Infusion in Patients With RA
Area under the curve AUC(0-inf) calculated based on serum samples, collected from baseline up to 24 weeks: Day 1, 4, 8, 15, 18, 29, 57, 85,113 and 169
Time frame: From baseline to 24 weeks
Population: PK Analysis Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GP2013 | AUC(0-inf) of GP2013, MabThera and Rituxan Following IV Infusion in Patients With RA | 7627.44 day*mcg/mL | Geometric Coefficient of Variation 38.6 |
| MabThera | AUC(0-inf) of GP2013, MabThera and Rituxan Following IV Infusion in Patients With RA | 6896.97 day*mcg/mL | Geometric Coefficient of Variation 40.56 |
| Rituxan | AUC(0-inf) of GP2013, MabThera and Rituxan Following IV Infusion in Patients With RA | 7536.89 day*mcg/mL | Geometric Coefficient of Variation 40.28 |
Comparison: PK bioequivalence is defined as AUC(0-inf) of the drugs being comparable, i.e. the two-sided 90% CI for the ratio of the geometric means (GP2013/MabThera) is within the predefined bioequivalence limits of 0.8 to 1.25.90% CI: [1.01, 1.21]
Comparison: PK bioequivalence is defined as AUC(0-inf) of the drugs being comparable, i.e. the two-sided 90% CI for the ratio of the geometric means (GP2013/MabThera) is within the predefined bioequivalence limits of 0.8 to 1.25.90% CI: [0.925, 1.108]
Comparison: PK bioequivalence is defined as AUC(0-inf) of the drugs being comparable, i.e. the two-sided 90% CI for the ratio of the geometric means (GP2013/MabThera) is within the predefined bioequivalence limits of 0.8 to 1.25.90% CI: [0.989, 1.208]
Secondary
Area Under the Effect Curve From Baseline to Day 14 (AUEC(0-14d)) of Percent B-cells of GP2013, MabThera and Rituxan in Patients With RA
Area under the effect curve of percent change of peripheral B-cell count from baseline to Day 14 (AUEC(0-14d)) of GP2013, MabThera and Rituxan in patients with RA
Time frame: 14 days
Population: PK analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GP2013 | Area Under the Effect Curve From Baseline to Day 14 (AUEC(0-14d)) of Percent B-cells of GP2013, MabThera and Rituxan in Patients With RA | 1226.53 % * day | Geometric Coefficient of Variation 2.83 |
| MabThera | Area Under the Effect Curve From Baseline to Day 14 (AUEC(0-14d)) of Percent B-cells of GP2013, MabThera and Rituxan in Patients With RA | 1201.15 % * day | Geometric Coefficient of Variation 8.91 |
| Rituxan | Area Under the Effect Curve From Baseline to Day 14 (AUEC(0-14d)) of Percent B-cells of GP2013, MabThera and Rituxan in Patients With RA | 1240.57 % * day | Geometric Coefficient of Variation 1.95 |
Comparison: To conclude equivalence the 95% CI must be entirely within the standard equivalencelimits of 0.8-1.2595% CI: [0.974, 1.004]
Comparison: To conclude equivalence the 95% CI must be entirely within the standard equivalencelimits of 0.8-1.2595% CI: [1.003, 1.04]
Comparison: To conclude equivalence the 95% CI must be entirely within the standard equivalence limits of 0.8-1.2595% CI: [1.016, 1.05]
Secondary
Change From Baseline in DAS28(CRP) at Week 24
Change from baseline in Disease Activity Score 28 joint count - C-reactive proteine DAS28(CRP) at Week 24. In order to calculate the DAS28(CRP) the number of tender joints and swollen joints were assessed using 28-joint count (tender28 and swollen28).The patient's global assessment of disease activity (GH) measured on a Visual Analogue Scale (VAS from 0mm - best to 100mm - worst) was obtained. DAS28(CRP) = 0.56 \* sqrt(tender28) + 0.28\* sqrt(swollen28) + 0.36 \* ln(CRP+1) + 0.014 \* GH + 0.96 The DAS28(CRP) provides a number on a scale from 0 to 10 indicating the current activity of the RA, while lower values correspond with less disease activity. A decrease in DAS28 signifies a clinical improvement.
Time frame: 24 weeks
Population: PP analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GP2013 | Change From Baseline in DAS28(CRP) at Week 24 | -2.07 units on a scale | Standard Error 0.103 |
| MabThera | Change From Baseline in DAS28(CRP) at Week 24 | -2.23 units on a scale | Standard Error 0.143 |
| Rituxan | Change From Baseline in DAS28(CRP) at Week 24 | -1.99 units on a scale | Standard Error 0.126 |
| GP2013 Part I | Change From Baseline in DAS28(CRP) at Week 24 | -2.16 units on a scale | Standard Error 0.142 |
Comparison: To conclude non-inferiority the upper 95% CI should be less than or equal to 0.6. This margin was statistically justified by the results of the REFLEX (Randomized Evaluation of Long-Term Efficacy of Rituximab in RA) trial (Cohen et al 2006) providing a 95% CI for the mean difference between rituximab/MTX and MTX alone of (-1.74;-1.25). The margin of 0.6 was determined by retaining more than 50% of the reference treatment effect which was considered clinically acceptable.95% CI: [-0.397, 0.24]
Comparison: To conclude non-inferiority the upper 95% CI should be less than or equal to 0.6. This margin was statistically justified by the results of the REFLEX (Randomized Evaluation of Long-Term Efficacy of Rituximab in RA) trial (Cohen et al 2006) providing a 95% CI for the mean difference between rituximab/MTX and MTX alone of (-1.74;-1.25). The margin of 0.6 was determined by retaining more than 50% of the reference treatment effect which was considered clinically acceptable.95% CI: [-0.328, 0.462]
Secondary
Maximum Serum Concentration (Cmax) of GP2013, MabThera and Rituxan Following IV Infusion in Patients With RA
Maximum serum concentration (Cmax) after the first infusion of GP2013, MabThera and Rituxan in patients with RA. Samples collected from baseline up to 24 weeks: Day 1, 4, 8, 15, 18, 29, 57, 85,113 and 169.
Time frame: From baseline to week 24
Population: PK Analysis Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GP2013 | Maximum Serum Concentration (Cmax) of GP2013, MabThera and Rituxan Following IV Infusion in Patients With RA | 361.53 mcg/mL | Geometric Coefficient of Variation 40.82 |
| MabThera | Maximum Serum Concentration (Cmax) of GP2013, MabThera and Rituxan Following IV Infusion in Patients With RA | 319.80 mcg/mL | Geometric Coefficient of Variation 42.75 |
| Rituxan | Maximum Serum Concentration (Cmax) of GP2013, MabThera and Rituxan Following IV Infusion in Patients With RA | 335.88 mcg/mL | Geometric Coefficient of Variation 42.65 |
Comparison: To conclude bioequivalence the 90% CI must be entirely within the standard equivalence limits of 0.8-1.25.90% CI: [0.979, 1.184]
Comparison: To conclude bioequivalence the 90% CI must be entirely within the standard equivalence limits of 0.8-1.2590% CI: [1.027, 1.244]
Comparison: To conclude bioequivalence the 90% CI must be entirely within the standard equivalence limits of 0.8-1.25.90% CI: [0.946, 1.167]
Secondary
Number of Patients With ACR20 (CRP) Response
A patient will be considered as improved according the ACR20 criteria * at least 20 % improvement from baseline in tender joint count, using the 68-joint count * at least 20 % improvement from baseline in swollen joint count, using the 66-joint count * and at least 20% improvement from baseline in a least 3 of the following 5 measures: * Patient's assessment of RA pain (VAS 100 mm) * Patient's global assessment of disease activity (VAS 100 mm) * Physician's global assessment of disease activity (VAS 100 mm) * Patient self-assessed disability (Health Assessment Questionnaire disability index) * Acute phase reactant (C-reactive protein or erythrocyte sedimentation rate)
Time frame: 24 weeks
Population: PP analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GP2013 | Number of Patients With ACR20 (CRP) Response | 86 Participants |
| MabThera | Number of Patients With ACR20 (CRP) Response | 55 Participants |
| Rituxan | Number of Patients With ACR20 (CRP) Response | 50 Participants |
| GP2013 Part I | Number of Patients With ACR20 (CRP) Response | 56 Participants |
Comparison: To conclude non-inferiority the lower 95% CI should be greater than -15.0%.95% CI: [-3.54, 23.08]
Comparison: To conclude non-inferiority the lower 95% CI should be greater than -15.0%.95% CI: [-14.74, 13.6]
Secondary
Participant Response as Assessed by EULAR Response Criteria
Present DAS28 ≤ 3.2 (low): good response (if improvement \> 1.2), moderate response (if improvement \>0.6 and ≤ 1.2), no response (if improvement ≤ 0.6). Present DAS28 \> 3.2 to ≤ 5.1 (moderate): moderate response (if improvement \> 1.2), moderate response (if improvement \>0.6 and ≤ 1.2), no response (if improvement ≤ 0.6). Present DAS28 \> 5.1 (high): moderate response (if improvement \> 1.2), no response (if improvement \>0.6 and ≤ 1.2), no response (if improvement ≤ 0.6).
Time frame: At week 24
Population: PP analysis set
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GP2013 | Participant Response as Assessed by EULAR Response Criteria | Good response | 0 Participants |
| GP2013 | Participant Response as Assessed by EULAR Response Criteria | No response | 15 Participants |
| GP2013 | Participant Response as Assessed by EULAR Response Criteria | Moderate response | 101 Participants |
| MabThera | Participant Response as Assessed by EULAR Response Criteria | Good response | 0 Participants |
| MabThera | Participant Response as Assessed by EULAR Response Criteria | No response | 16 Participants |
| MabThera | Participant Response as Assessed by EULAR Response Criteria | Moderate response | 61 Participants |
| Rituxan | Participant Response as Assessed by EULAR Response Criteria | Moderate response | 67 Participants |
| Rituxan | Participant Response as Assessed by EULAR Response Criteria | Good response | 0 Participants |
| Rituxan | Participant Response as Assessed by EULAR Response Criteria | No response | 9 Participants |
| GP2013 Part I | Participant Response as Assessed by EULAR Response Criteria | Good response | 0 Participants |
| GP2013 Part I | Participant Response as Assessed by EULAR Response Criteria | No response | 12 Participants |
| GP2013 Part I | Participant Response as Assessed by EULAR Response Criteria | Moderate response | 63 Participants |
Secondary
Summary of Disease Activity According to CDAI
In order to calculate the Clinical Disease Activity Index (CDAI) the number of tender and swollen joints were assessed using the 28 -joint count (tender28 and swollen28). The patient's global assessment of disease activity and the physician's global assessment of disease activity were measured using a Visual Analogue Scale (VAS) of 10 cm (from 0=best to 10=worst). CDAI = tender28 + swollen28 + patient's global assessment (in cm) + physician's global assessment (in cm)
Time frame: At week 24
Population: PP analysis set
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GP2013 | Summary of Disease Activity According to CDAI | High disease activity | 26 Participants |
| GP2013 | Summary of Disease Activity According to CDAI | Moderate disease activity | 45 Participants |
| GP2013 | Summary of Disease Activity According to CDAI | Low disease activity | 41 Participants |
| GP2013 | Summary of Disease Activity According to CDAI | Remission | 7 Participants |
| MabThera | Summary of Disease Activity According to CDAI | Remission | 3 Participants |
| MabThera | Summary of Disease Activity According to CDAI | Low disease activity | 25 Participants |
| MabThera | Summary of Disease Activity According to CDAI | Moderate disease activity | 32 Participants |
| MabThera | Summary of Disease Activity According to CDAI | High disease activity | 20 Participants |
| Rituxan | Summary of Disease Activity According to CDAI | Low disease activity | 30 Participants |
| Rituxan | Summary of Disease Activity According to CDAI | Remission | 6 Participants |
| Rituxan | Summary of Disease Activity According to CDAI | Moderate disease activity | 24 Participants |
| Rituxan | Summary of Disease Activity According to CDAI | High disease activity | 18 Participants |
| GP2013 Part I | Summary of Disease Activity According to CDAI | Moderate disease activity | 26 Participants |
| GP2013 Part I | Summary of Disease Activity According to CDAI | High disease activity | 18 Participants |
| GP2013 Part I | Summary of Disease Activity According to CDAI | Remission | 12 Participants |
| GP2013 Part I | Summary of Disease Activity According to CDAI | Low disease activity | 19 Participants |
Secondary
Summary of Disease Activity According to SDAI
In order to calculate the Simplified Disease Activity Index (SDAI) the number of tender and swollen joints were assessed using the 28 -joint count (tender28 and swollen28). The patient's global assessment of disease activity and the physician's global assessment of disease activity were measured using a Visual Analogue Scale (VAS) of 10 cm (from 0=best to 10=worst). SDAI = CDAI + CRP (in mg/dL) (CDAI = tender28 + swollen28 + patient's global assessment (in cm) + physician's global assessment (in cm))
Time frame: At week 24
Population: PP analysis set
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GP2013 | Summary of Disease Activity According to SDAI | High disease activity | 20 Participants |
| GP2013 | Summary of Disease Activity According to SDAI | Remission | 8 Participants |
| GP2013 | Summary of Disease Activity According to SDAI | Moderate disease activity | 48 Participants |
| GP2013 | Summary of Disease Activity According to SDAI | Low disease activity | 41 Participants |
| MabThera | Summary of Disease Activity According to SDAI | Moderate disease activity | 34 Participants |
| MabThera | Summary of Disease Activity According to SDAI | Low disease activity | 26 Participants |
| MabThera | Summary of Disease Activity According to SDAI | High disease activity | 15 Participants |
| MabThera | Summary of Disease Activity According to SDAI | Remission | 2 Participants |
| Rituxan | Summary of Disease Activity According to SDAI | Moderate disease activity | 27 Participants |
| Rituxan | Summary of Disease Activity According to SDAI | High disease activity | 13 Participants |
| Rituxan | Summary of Disease Activity According to SDAI | Low disease activity | 31 Participants |
| Rituxan | Summary of Disease Activity According to SDAI | Remission | 6 Participants |
| GP2013 Part I | Summary of Disease Activity According to SDAI | High disease activity | 15 Participants |
| GP2013 Part I | Summary of Disease Activity According to SDAI | Moderate disease activity | 29 Participants |
| GP2013 Part I | Summary of Disease Activity According to SDAI | Remission | 12 Participants |
| GP2013 Part I | Summary of Disease Activity According to SDAI | Low disease activity | 18 Participants |
Other Pre-specified
Number of Patients With at Least One Anti-Drug-Antibody (ADA) Positive Serum Sample
Number of patients with at least one post-baseline Anti-Drug-Antibody (ADA) positive serum sample until the last study visit. Sampling was at Day 1, 29, 113, 169, 267, 365, optional visit 1 (could be at any time between day 169 - week 24 and day 365 - week 52 for patients, who received a 2nd treatment course) and optional visit 2 (only applicable for patients, who received a 2nd treatment course, 26 weeks thereafter, if this was after day 365 - week 52).
Time frame: through study completion, an average of 1 year
Population: Patients with positive ADA results at randomization were excluded from analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GP2013 | Number of Patients With at Least One Anti-Drug-Antibody (ADA) Positive Serum Sample | 21 participants |
| MabThera | Number of Patients With at Least One Anti-Drug-Antibody (ADA) Positive Serum Sample | 18 participants |
| Rituxan | Number of Patients With at Least One Anti-Drug-Antibody (ADA) Positive Serum Sample | 11 participants |