Rheumatoid Arthritis
Conditions
Brief summary
The primary objective of this study is to assess the safety and tolerability of combined treatment with atacicept and rituximab in subjects with active rheumatoid arthritis (RA) receiving re-treatment with rituximab.
Interventions
BIOLOGICALRituximab
Rituximab will be administered as an intravenous infusion at a dose of 1000 mg at Weeks 1 and 3.
DRUGAtacicept
Atacicept will be administered at a dose of 150 mg subcutaneously once a week from Week 7 to 32.
Placebo matched to atacicept will be administered subcutaneously once a week from Week 7 to 32.
Sponsors
Merck KGaA, Darmstadt, Germany
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
* Male and female subjects * Greater than and equal to (\>=) 18 years of age at the time of Informed Consent * Who have rheumatoid arthritis satisfying American College of Rheumatology (ACR) criteria with a disease history of at least 12 months * Subjects must have active disease defined by DAS28 \>3.2 * Subjects must have received previous treatment with rituximab and must be candidates for re-treatment with rituximab * Female subjects of childbearing potential must be willing to avoid pregnancy by using an adequate method of contraception for 4 weeks before study day 1 (SD1), during the treatment period and for 12 months after the last dose of rituximab, and must have a negative urine pregnancy test at the screening visit and SD1 * Other protocol defined inclusion criteria could apply
Exclusion criteria
* Current neurological disease excluding migraine * Inflammatory joint disease other than rheumatoid arthritis * Any contraindication to rituximab as per national label * Use of disease-modifying anti-rheumatic drugs (DMARDs; including methotrexate) for less than 3 months or change in dosing regimen within 28 days before SD1, or methotrexate dose regimen \>25 mg/week * Participation in any interventional clinical trial within 1 month before SD1 (or within 5 half-lives of the investigated compound before SD1, whichever is longer) * Prednisone dose regimen \>10 mg/day (or equivalent), or change in steroid dosing regimen within 28 days before SD1 * Active or latent tuberculosis within the year before screening or major infection requiring hospitalization or intravenous anti-infectives within 28 days before SD1 * Serum Immunoglobulin G (IgG) below 6 gram per liter (g/L) * Known hypersensitivity to atacicept or to any of the components of the formulated atacicpet * Known hypersensitivity to rituximab, to any of the components of the formulated rituximab or to murine proteins * Breastfeeding or pregnancy * Other protocol defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Anti-pneumococcus Titer at Week 32 | Baseline, Week 32 | Percent change from baseline was calculated as (\[Week 32 value minus baseline value\] multiplied by 100) divided by baseline value. |
| Percentage of Participants With Immunoglobulin G (IgG) Level Less Than 3 Gram Per Liter (g/L) | Week 64 | — |
| Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Baseline, Week 32 | Vital signs assessed included blood pressure (systolic and diastolic), pulse and body temperature. Routine safety lab parameters evaluated included red blood cell (RBC), hemoglobin, hematocrit, platelets, mean cellular hemoglobin (MCH), MCH concentration, MCH volume, white blood cell (WBC), lymphocytes, monocytes, eosinophils, basophils, neutrophils, gamma glutamyl transferase (GGT), alanine aminotransferase (ALT), albumin, alkaline phosphatase (AP), aspartate aminotransferase (AST), bilirubin, calcium, creatinine, glucose, potassium, total protein, sodium, uric acid, and blood urea nitrogen. Percent change from baseline was calculated as (\[Week 32 value minus baseline value\] multiplied by 100) divided by baseline value. |
| Percent Change From Baseline in Anti-tetanus and Anti-diphteria Immunization Titer at Week 32 | Baseline, Week 32 | Percent change from baseline was calculated as (\[Week 32 value minus baseline value\] multiplied by 100) divided by baseline value. |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline up to Week 64 | An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. An SAE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Disease Activity Score in 28 Joints (DAS28) Based on CRP (DAS28-CRP) at Week 32 | Baseline, Week 32 | DAS28-CRP incorporates non-graded joint counts for tenderness and swelling based on a total of 28 joints, CRP as a marker of inflammation, and a general health assessment using a 100 mm visual analog scale (the participant's global assessment of disease activity). DAS28 score ranges between 0 and 10 representing current disease activity. A value above 5.1 represents high disease activity, a value below 3.2 represents low disease activity, and a value below 2.6 represents remission. |
| Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Baseline, Week 3, 7, 12, 16, 26 and 32 | Flow cytometric analysis of lymphocyte populations using four-color fluorescence-activated cell sorting was performed for the analysis of total, mature and memory B cell levels. |
| Percentage of Participants Achieving American College of Rheumatology 20 Response Based on C-reactive Protein (ACR20-CRP), ACR50-CRP and ACR70-CRP at Week 32 | Week 32 | ACR20-CRP response: greater than or equal to (\>=) 20 percent (%) improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with \>=20% improvement in at least 3 of the following: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP). ACR50-CRP and ACR70-CRP response are defined as \>=50% and \>=70% improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) respectively together with \>=50% and \>=70% improvement in at least 3 of the following respectively: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) CRP. |
Countries
France, Netherlands, Sweden, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rituximab Plus Atacicept Rituximab was administered as an intravenous infusion at a dose of 1000 milligram (mg) at Weeks 1 and 3, followed by atacicept 150 mg subcutaneously once a week from Week 7 to 32. | 18 |
| Rituximab Plus Placebo Rituximab was administered as an intravenous infusion at a dose of 1000 milligram (mg) at Weeks 1 and 3, followed by placebo matched to atacicept subcutaneously once a week from Week 7 to 32. | 9 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Other | 1 | 0 |
Baseline characteristics
| Characteristic | Rituximab Plus Atacicept | Rituximab Plus Placebo | Total |
|---|---|---|---|
| Age, Continuous | 57.0 years STANDARD_DEVIATION 11 | 57.7 years STANDARD_DEVIATION 11.5 | 57.2 years STANDARD_DEVIATION 11 |
| Gender Female | 12 Participants | 8 Participants | 20 Participants |
| Gender Male | 6 Participants | 1 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 17 / 18 | 9 / 9 |
| serious Total, serious adverse events | 6 / 18 | 2 / 9 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. An SAE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Time frame: Baseline up to Week 64
Population: Safety population included all participants who received at least one dose of atacicept or placebo.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab Plus Atacicept | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 17 Participants |
| Rituximab Plus Atacicept | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 6 Participants |
| Rituximab Plus Placebo | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 2 Participants |
| Rituximab Plus Placebo | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 9 Participants |
Primary
Percentage of Participants With Immunoglobulin G (IgG) Level Less Than 3 Gram Per Liter (g/L)
Time frame: Week 64
Population: Safety population included all participants who received at least one dose of atacicept or placebo. Here. N (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab Plus Atacicept | Percentage of Participants With Immunoglobulin G (IgG) Level Less Than 3 Gram Per Liter (g/L) | 0 percentage of participants |
| Rituximab Plus Placebo | Percentage of Participants With Immunoglobulin G (IgG) Level Less Than 3 Gram Per Liter (g/L) | 0 percentage of participants |
Primary
Percent Change From Baseline in Anti-pneumococcus Titer at Week 32
Percent change from baseline was calculated as (\[Week 32 value minus baseline value\] multiplied by 100) divided by baseline value.
Time frame: Baseline, Week 32
Population: Safety population included all participants who received at least one dose of atacicept or placebo. Here, N (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rituximab Plus Atacicept | Percent Change From Baseline in Anti-pneumococcus Titer at Week 32 | -18.49 percent change |
| Rituximab Plus Placebo | Percent Change From Baseline in Anti-pneumococcus Titer at Week 32 | 0.00 percent change |
Primary
Percent Change From Baseline in Anti-tetanus and Anti-diphteria Immunization Titer at Week 32
Percent change from baseline was calculated as (\[Week 32 value minus baseline value\] multiplied by 100) divided by baseline value.
Time frame: Baseline, Week 32
Population: Safety population included all participants who received at least one dose of atacicept or placebo. Here. N (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Rituximab Plus Atacicept | Percent Change From Baseline in Anti-tetanus and Anti-diphteria Immunization Titer at Week 32 | Anti-tetanus Immunization Titer | -17.98 percent change |
| Rituximab Plus Atacicept | Percent Change From Baseline in Anti-tetanus and Anti-diphteria Immunization Titer at Week 32 | Anti-diphtheria Immunization Titer | -33.68 percent change |
| Rituximab Plus Placebo | Percent Change From Baseline in Anti-tetanus and Anti-diphteria Immunization Titer at Week 32 | Anti-tetanus Immunization Titer | 0.00 percent change |
| Rituximab Plus Placebo | Percent Change From Baseline in Anti-tetanus and Anti-diphteria Immunization Titer at Week 32 | Anti-diphtheria Immunization Titer | 8.41 percent change |
Primary
Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32
Vital signs assessed included blood pressure (systolic and diastolic), pulse and body temperature. Routine safety lab parameters evaluated included red blood cell (RBC), hemoglobin, hematocrit, platelets, mean cellular hemoglobin (MCH), MCH concentration, MCH volume, white blood cell (WBC), lymphocytes, monocytes, eosinophils, basophils, neutrophils, gamma glutamyl transferase (GGT), alanine aminotransferase (ALT), albumin, alkaline phosphatase (AP), aspartate aminotransferase (AST), bilirubin, calcium, creatinine, glucose, potassium, total protein, sodium, uric acid, and blood urea nitrogen. Percent change from baseline was calculated as (\[Week 32 value minus baseline value\] multiplied by 100) divided by baseline value.
Time frame: Baseline, Week 32
Population: Safety population included all participants who received at least one dose of atacicept or placebo. Here, N (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure and 'n' signifies those participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Diastolic Blood Pressure (n = 12, 9) | 1.09 Percent change | Standard Deviation 11.19 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Temperature (n = 10, 8) | 0.23 Percent change | Standard Deviation 1.05 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Hemoglobin (n = 12, 9) | 2.55 Percent change | Standard Deviation 5.32 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Platelets (n = 12, 9) | -6.80 Percent change | Standard Deviation 21.21 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | MCH Concentration (n = 12, 9) | -0.18 Percent change | Standard Deviation 2.01 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Systolic Blood Pressure (n = 12, 9) | 3.74 Percent change | Standard Deviation 11.76 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Pulse (n = 12, 9) | 10.21 Percent change | Standard Deviation 19.93 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | RBC (n = 12, 9) | 3.10 Percent change | Standard Deviation 5.3 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Hematocrit (n = 12, 9) | 2.39 Percent change | Standard Deviation 6.3 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | MCH (n = 12, 9) | -0.32 Percent change | Standard Deviation 5.03 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | MCH Volume (n = 12, 9) | -0.06 Percent change | Standard Deviation 4.98 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | WBC(n = 12, 9) | -14.59 Percent change | Standard Deviation 36.85 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Lymphocytes (n = 12, 9) | 0.27 Percent change | Standard Deviation 30.11 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Monocytes (n = 12, 9) | 5.01 Percent change | Standard Deviation 70.44 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Eosinophils (n = 12, 9) | 34.11 Percent change | Standard Deviation 103.78 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Basophils (n = 12, 9) | -20.45 Percent change | Standard Deviation 58.61 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Neutrophils (n = 12, 9) | -11.29 Percent change | Standard Deviation 57.75 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | GGT (n = 12, 9) | -3.21 Percent change | Standard Deviation 30.37 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | ALT (n = 12, 9) | 17.52 Percent change | Standard Deviation 27.89 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Albumin (n = 12, 9) | 6.22 Percent change | Standard Deviation 6.34 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | AP (n = 12, 9) | 4.85 Percent change | Standard Deviation 18.86 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | AST (n = 12, 9) | 14.53 Percent change | Standard Deviation 30.87 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Bilirubin Total (n = 12, 9) | 15.09 Percent change | Standard Deviation 42.78 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Calcium (n = 12, 9) | -1.07 Percent change | Standard Deviation 5.04 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Creatinine (n = 12, 9) | -3.29 Percent change | Standard Deviation 10.3 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Glucose (n = 12, 9) | 3.71 Percent change | Standard Deviation 18.55 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Potassium (n = 12, 9) | -0.93 Percent change | Standard Deviation 6.34 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Total Protein (n = 12, 9) | -2.83 Percent change | Standard Deviation 7.08 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Sodium (n = 12, 9) | 1.21 Percent change | Standard Deviation 1.46 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Uric Acid (n = 12, 9) | -2.95 Percent change | Standard Deviation 12.6 |
| Rituximab Plus Atacicept | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Blood Urea Nitrogen (n = 12, 9) | 1.63 Percent change | Standard Deviation 27.04 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Blood Urea Nitrogen (n = 12, 9) | -7.42 Percent change | Standard Deviation 26.02 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Basophils (n = 12, 9) | 32.41 Percent change | Standard Deviation 117.44 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | RBC (n = 12, 9) | 4.94 Percent change | Standard Deviation 7.18 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Calcium (n = 12, 9) | 2.61 Percent change | Standard Deviation 4.72 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Hemoglobin (n = 12, 9) | 4.93 Percent change | Standard Deviation 6.18 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Hematocrit (n = 12, 9) | 6.05 Percent change | Standard Deviation 6.15 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Neutrophils (n = 12, 9) | -13.09 Percent change | Standard Deviation 24.01 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Total Protein (n = 12, 9) | 4.17 Percent change | Standard Deviation 6.57 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | MCH Concentration (n = 12, 9) | -1.41 Percent change | Standard Deviation 1.47 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | MCH Volume (n = 12, 9) | 1.39 Percent change | Standard Deviation 2.73 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Monocytes (n = 12, 9) | 1.88 Percent change | Standard Deviation 38.51 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | ALT (n = 12, 9) | 17.79 Percent change | Standard Deviation 53.23 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | GGT (n = 12, 9) | 10.17 Percent change | Standard Deviation 53.33 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Systolic Blood Pressure (n = 12, 9) | -6.29 Percent change | Standard Deviation 13.8 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Pulse (n = 12, 9) | -8.54 Percent change | Standard Deviation 11.98 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Diastolic Blood Pressure (n = 12, 9) | 4.89 Percent change | Standard Deviation 10.09 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Creatinine (n = 12, 9) | 5.89 Percent change | Standard Deviation 5.26 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Temperature (n = 10, 8) | -0.44 Percent change | Standard Deviation 0.86 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Uric Acid (n = 12, 9) | -0.72 Percent change | Standard Deviation 6.1 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Albumin (n = 12, 9) | 6.43 Percent change | Standard Deviation 8.1 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Platelets (n = 12, 9) | -2.49 Percent change | Standard Deviation 37.62 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Glucose (n = 12, 9) | 7.99 Percent change | Standard Deviation 22.71 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | MCH (n = 12, 9) | 0.22 Percent change | Standard Deviation 3.21 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | AP (n = 12, 9) | -5.41 Percent change | Standard Deviation 16.48 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Sodium (n = 12, 9) | 0.25 Percent change | Standard Deviation 1.63 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | WBC(n = 12, 9) | -9.70 Percent change | Standard Deviation 19.15 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | AST (n = 12, 9) | 6.73 Percent change | Standard Deviation 36.47 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Lymphocytes (n = 12, 9) | -5.68 Percent change | Standard Deviation 23 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Potassium (n = 12, 9) | 4.67 Percent change | Standard Deviation 9.37 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Bilirubin Total (n = 12, 9) | 4.76 Percent change | Standard Deviation 14.29 |
| Rituximab Plus Placebo | Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 | Eosinophils (n = 12, 9) | -7.51 Percent change | Standard Deviation 34.58 |
Secondary
Change From Baseline in Disease Activity Score in 28 Joints (DAS28) Based on CRP (DAS28-CRP) at Week 32
DAS28-CRP incorporates non-graded joint counts for tenderness and swelling based on a total of 28 joints, CRP as a marker of inflammation, and a general health assessment using a 100 mm visual analog scale (the participant's global assessment of disease activity). DAS28 score ranges between 0 and 10 representing current disease activity. A value above 5.1 represents high disease activity, a value below 3.2 represents low disease activity, and a value below 2.6 represents remission.
Time frame: Baseline, Week 32
Population: ITT population included all randomized participants. Here 'n' signifies those participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab Plus Atacicept | Change From Baseline in Disease Activity Score in 28 Joints (DAS28) Based on CRP (DAS28-CRP) at Week 32 | Baseline (n = 18, 9) | 5.50 Units on a scale | Standard Deviation 0.99 |
| Rituximab Plus Atacicept | Change From Baseline in Disease Activity Score in 28 Joints (DAS28) Based on CRP (DAS28-CRP) at Week 32 | Change at Week 32 (n = 12, 9) | 3.85 Units on a scale | Standard Deviation 0.98 |
| Rituximab Plus Placebo | Change From Baseline in Disease Activity Score in 28 Joints (DAS28) Based on CRP (DAS28-CRP) at Week 32 | Baseline (n = 18, 9) | 5.81 Units on a scale | Standard Deviation 1.04 |
| Rituximab Plus Placebo | Change From Baseline in Disease Activity Score in 28 Joints (DAS28) Based on CRP (DAS28-CRP) at Week 32 | Change at Week 32 (n = 12, 9) | 4.25 Units on a scale | Standard Deviation 1.1 |
Secondary
Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells
Flow cytometric analysis of lymphocyte populations using four-color fluorescence-activated cell sorting was performed for the analysis of total, mature and memory B cell levels.
Time frame: Baseline, Week 3, 7, 12, 16, 26 and 32
Population: Safety population included all participants who received at least one dose of atacicept or placebo. Here 'n' signifies those participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Rituximab Plus Atacicept | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Total B cells (Week 7: n=17, 8) | -100.00 percent change |
| Rituximab Plus Atacicept | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Total B cells (Week 26: n=12, 9) | -100.00 percent change |
| Rituximab Plus Atacicept | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Mature B Cells (Week 32: n=12, 9) | -99.35 percent change |
| Rituximab Plus Atacicept | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Total B cells (Week 32: n=12, 9) | -86.99 percent change |
| Rituximab Plus Atacicept | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Memory B cells (Week 12: n=16, 9) | -100.00 percent change |
| Rituximab Plus Atacicept | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Mature B Cells (Week 3: n=18, 9) | -100.00 percent change |
| Rituximab Plus Atacicept | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Mature B Cells (Week 12: n=16, 9) | -100.00 percent change |
| Rituximab Plus Atacicept | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Mature B Cells (Week 16: n=15, 9) | -100.00 percent change |
| Rituximab Plus Atacicept | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Memory B cells (Week 16: n=15, 9) | -100.00 percent change |
| Rituximab Plus Atacicept | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Memory B cells (Week 3: n=18, 9) | -100.00 percent change |
| Rituximab Plus Atacicept | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Total B cells (Week 3: n=18, 9) | -100.00 percent change |
| Rituximab Plus Atacicept | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Memory B cells (Week 7: n=17, 8) | -100.00 percent change |
| Rituximab Plus Atacicept | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Mature B Cells (Week 7: n=17, 8) | -100.00 percent change |
| Rituximab Plus Atacicept | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Total B cells (Week 12: n=16, 9) | -100.00 percent change |
| Rituximab Plus Atacicept | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Memory B cells (Week 26: n=12, 9) | -100.00 percent change |
| Rituximab Plus Atacicept | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Mature B Cells (Week 26: n=12, 9) | -100.00 percent change |
| Rituximab Plus Atacicept | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Memory B cells (Week 32: n=12, 9) | -83.33 percent change |
| Rituximab Plus Atacicept | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Total B cells (Week 16: n=15, 9) | -100.00 percent change |
| Rituximab Plus Placebo | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Memory B cells (Week 32: n=12, 9) | -50.00 percent change |
| Rituximab Plus Placebo | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Mature B Cells (Week 3: n=18, 9) | -100.00 percent change |
| Rituximab Plus Placebo | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Mature B Cells (Week 7: n=17, 8) | -100.00 percent change |
| Rituximab Plus Placebo | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Mature B Cells (Week 16: n=15, 9) | -100.00 percent change |
| Rituximab Plus Placebo | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Mature B Cells (Week 26: n=12, 9) | -100.00 percent change |
| Rituximab Plus Placebo | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Memory B cells (Week 12: n=16, 9) | -100.00 percent change |
| Rituximab Plus Placebo | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Total B cells (Week 7: n=17, 8) | -99.69 percent change |
| Rituximab Plus Placebo | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Total B cells (Week 12: n=16, 9) | -100.00 percent change |
| Rituximab Plus Placebo | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Total B cells (Week 16: n=15, 9) | -100.00 percent change |
| Rituximab Plus Placebo | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Total B cells (Week 26: n=12, 9) | -94.74 percent change |
| Rituximab Plus Placebo | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Total B cells (Week 32: n=12, 9) | -68.11 percent change |
| Rituximab Plus Placebo | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Mature B Cells (Week 12: n=16, 9) | -100.00 percent change |
| Rituximab Plus Placebo | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Mature B Cells (Week 32: n=12, 9) | -84.47 percent change |
| Rituximab Plus Placebo | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Memory B cells (Week 3: n=18, 9) | -100.00 percent change |
| Rituximab Plus Placebo | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Memory B cells (Week 7: n=17, 8) | -100.00 percent change |
| Rituximab Plus Placebo | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Memory B cells (Week 16: n=15, 9) | -100.00 percent change |
| Rituximab Plus Placebo | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Memory B cells (Week 26: n=12, 9) | -88.89 percent change |
| Rituximab Plus Placebo | Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells | Total B cells (Week 3: n=18, 9) | -100.00 percent change |
Secondary
Percentage of Participants Achieving American College of Rheumatology 20 Response Based on C-reactive Protein (ACR20-CRP), ACR50-CRP and ACR70-CRP at Week 32
ACR20-CRP response: greater than or equal to (\>=) 20 percent (%) improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with \>=20% improvement in at least 3 of the following: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP). ACR50-CRP and ACR70-CRP response are defined as \>=50% and \>=70% improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) respectively together with \>=50% and \>=70% improvement in at least 3 of the following respectively: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) CRP.
Time frame: Week 32
Population: ITT population included all randomized participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab Plus Atacicept | Percentage of Participants Achieving American College of Rheumatology 20 Response Based on C-reactive Protein (ACR20-CRP), ACR50-CRP and ACR70-CRP at Week 32 | ACR70-CRP | 5.6 percentage of participants |
| Rituximab Plus Atacicept | Percentage of Participants Achieving American College of Rheumatology 20 Response Based on C-reactive Protein (ACR20-CRP), ACR50-CRP and ACR70-CRP at Week 32 | ACR20-CRP | 33.3 percentage of participants |
| Rituximab Plus Atacicept | Percentage of Participants Achieving American College of Rheumatology 20 Response Based on C-reactive Protein (ACR20-CRP), ACR50-CRP and ACR70-CRP at Week 32 | ACR50-CRP | 11.1 percentage of participants |
| Rituximab Plus Placebo | Percentage of Participants Achieving American College of Rheumatology 20 Response Based on C-reactive Protein (ACR20-CRP), ACR50-CRP and ACR70-CRP at Week 32 | ACR20-CRP | 22.2 percentage of participants |
| Rituximab Plus Placebo | Percentage of Participants Achieving American College of Rheumatology 20 Response Based on C-reactive Protein (ACR20-CRP), ACR50-CRP and ACR70-CRP at Week 32 | ACR50-CRP | 11.1 percentage of participants |
| Rituximab Plus Placebo | Percentage of Participants Achieving American College of Rheumatology 20 Response Based on C-reactive Protein (ACR20-CRP), ACR50-CRP and ACR70-CRP at Week 32 | ACR70-CRP | 0 percentage of participants |