Trial Outcomes & Findings for Atacicept in Combination With Rituximab in Subjects With Rheumatoid Arthritis (August III) (NCT NCT00664521)
NCT ID: NCT00664521
Last Updated: 2016-12-30
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
27 participants
Primary outcome timeframe
Baseline up to Week 64
Results posted on
2016-12-30
Participant Flow
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
18
|
9
|
|
Overall Study
COMPLETED
|
12
|
8
|
|
Overall Study
NOT COMPLETED
|
6
|
1
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
Adverse Event
|
4
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Other
|
1
|
0
|
Baseline Characteristics
Atacicept in Combination With Rituximab in Subjects With Rheumatoid Arthritis (August III)
Baseline characteristics by cohort
| Measure |
Rituximab Plus Atacicept
n=18 Participants
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.
|
Rituximab Plus Placebo
n=9 Participants
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.
|
Total
n=27 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
57.0 years
STANDARD_DEVIATION 11.0 • n=5 Participants
|
57.7 years
STANDARD_DEVIATION 11.5 • n=7 Participants
|
57.2 years
STANDARD_DEVIATION 11.0 • n=5 Participants
|
|
Gender
Female
|
12 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Gender
Male
|
6 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Week 64Population: Safety population included all participants who received at least one dose of atacicept or placebo.
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.
Outcome measures
| Measure |
Rituximab Plus Atacicept
n=18 Participants
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.
|
Rituximab Plus Placebo
n=9 Participants
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.
|
|---|---|---|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
SAEs
|
6 Participants
|
2 Participants
|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
AEs
|
17 Participants
|
9 Participants
|
PRIMARY outcome
Timeframe: Week 64Population: 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.
Outcome measures
| Measure |
Rituximab Plus Atacicept
n=11 Participants
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.
|
Rituximab Plus Placebo
n=5 Participants
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.
|
|---|---|---|
|
Percentage of Participants With Immunoglobulin G (IgG) Level Less Than 3 Gram Per Liter (g/L)
|
0 percentage of participants
|
0 percentage of participants
|
PRIMARY outcome
Timeframe: Baseline, Week 32Population: 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.
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.
Outcome measures
| Measure |
Rituximab Plus Atacicept
n=12 Participants
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.
|
Rituximab Plus Placebo
n=9 Participants
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.
|
|---|---|---|
|
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
|
-6.29 Percent change
Standard Deviation 13.80
|
|
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
|
4.89 Percent change
Standard Deviation 10.09
|
|
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
|
-8.54 Percent change
Standard Deviation 11.98
|
|
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
|
-0.44 Percent change
Standard Deviation 0.86
|
|
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 5.30
|
4.94 Percent change
Standard Deviation 7.18
|
|
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
|
4.93 Percent change
Standard Deviation 6.18
|
|
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 6.30
|
6.05 Percent change
Standard Deviation 6.15
|
|
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
|
-2.49 Percent change
Standard Deviation 37.62
|
|
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
|
-1.41 Percent change
Standard Deviation 1.47
|
|
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
|
1.39 Percent change
Standard Deviation 2.73
|
|
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
|
-5.68 Percent change
Standard Deviation 23.00
|
|
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
|
1.88 Percent change
Standard Deviation 38.51
|
|
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
|
-7.51 Percent change
Standard Deviation 34.58
|
|
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
|
-13.09 Percent change
Standard Deviation 24.01
|
|
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
|
4.67 Percent change
Standard Deviation 9.37
|
|
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
|
0.22 Percent change
Standard Deviation 3.21
|
|
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
|
2.61 Percent change
Standard Deviation 4.72
|
|
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
|
32.41 Percent change
Standard Deviation 117.44
|
|
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
|
10.17 Percent change
Standard Deviation 53.33
|
|
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
|
17.79 Percent change
Standard Deviation 53.23
|
|
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
|
-9.70 Percent change
Standard Deviation 19.15
|
|
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
|
6.43 Percent change
Standard Deviation 8.10
|
|
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
|
-5.41 Percent change
Standard Deviation 16.48
|
|
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
|
6.73 Percent change
Standard Deviation 36.47
|
|
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
|
4.76 Percent change
Standard Deviation 14.29
|
|
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 10.30
|
5.89 Percent change
Standard Deviation 5.26
|
|
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
|
7.99 Percent change
Standard Deviation 22.71
|
|
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
|
4.17 Percent change
Standard Deviation 6.57
|
|
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
|
0.25 Percent change
Standard Deviation 1.63
|
|
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 12.60
|
-0.72 Percent change
Standard Deviation 6.10
|
|
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
|
-7.42 Percent change
Standard Deviation 26.02
|
PRIMARY outcome
Timeframe: Baseline, Week 32Population: 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.
Percent change from baseline was calculated as (\[Week 32 value minus baseline value\] multiplied by 100) divided by baseline value.
Outcome measures
| Measure |
Rituximab Plus Atacicept
n=10 Participants
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.
|
Rituximab Plus Placebo
n=9 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in Anti-tetanus and Anti-diphteria Immunization Titer at Week 32
Anti-tetanus Immunization Titer
|
-17.98 percent change
Interval -34.29 to 0.0
|
0.00 percent change
Interval -7.67 to 23.68
|
|
Percent Change From Baseline in Anti-tetanus and Anti-diphteria Immunization Titer at Week 32
Anti-diphtheria Immunization Titer
|
-33.68 percent change
Interval -50.0 to 0.0
|
8.41 percent change
Interval 0.39 to 33.93
|
PRIMARY outcome
Timeframe: Baseline, Week 32Population: 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.
Percent change from baseline was calculated as (\[Week 32 value minus baseline value\] multiplied by 100) divided by baseline value.
Outcome measures
| Measure |
Rituximab Plus Atacicept
n=10 Participants
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.
|
Rituximab Plus Placebo
n=9 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in Anti-pneumococcus Titer at Week 32
|
-18.49 percent change
Interval -35.18 to 0.0
|
0.00 percent change
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: Week 32Population: ITT population included all randomized participants.
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.
Outcome measures
| Measure |
Rituximab Plus Atacicept
n=18 Participants
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.
|
Rituximab Plus Placebo
n=9 Participants
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.
|
|---|---|---|
|
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
|
22.2 percentage of participants
|
|
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
|
11.1 percentage of participants
|
|
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
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Week 32Population: ITT population included all randomized participants. Here 'n' signifies those participants who were evaluable for the specified category.
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.
Outcome measures
| Measure |
Rituximab Plus Atacicept
n=18 Participants
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.
|
Rituximab Plus Placebo
n=9 Participants
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.
|
|---|---|---|
|
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
|
5.81 Units on a scale
Standard Deviation 1.04
|
|
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
|
4.25 Units on a scale
Standard Deviation 1.10
|
SECONDARY outcome
Timeframe: Baseline, Week 3, 7, 12, 16, 26 and 32Population: 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.
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.
Outcome measures
| Measure |
Rituximab Plus Atacicept
n=18 Participants
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.
|
Rituximab Plus Placebo
n=9 Participants
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.
|
|---|---|---|
|
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
Interval -100.0 to -68.33
|
-100.00 percent change
Interval -100.0 to -100.0
|
|
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
Interval -100.0 to -100.0
|
-100.00 percent change
Interval -100.0 to -66.67
|
|
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
Interval -100.0 to -82.5
|
-88.89 percent change
Interval -100.0 to -25.0
|
|
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
Interval -100.0 to -25.0
|
-50.00 percent change
Interval -100.0 to -44.44
|
|
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
Interval -100.0 to -100.0
|
-100.00 percent change
Interval -100.0 to -100.0
|
|
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
Interval -100.0 to -100.0
|
-99.69 percent change
Interval -100.0 to -96.96
|
|
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
Interval -100.0 to -100.0
|
-100.00 percent change
Interval -100.0 to -100.0
|
|
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
Interval -100.0 to -100.0
|
-100.00 percent change
Interval -100.0 to -100.0
|
|
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
Interval -100.0 to -93.06
|
-94.74 percent change
Interval -100.0 to -71.43
|
|
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
Interval -98.26 to -50.0
|
-68.11 percent change
Interval -100.0 to -35.0
|
|
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
Interval -100.0 to -100.0
|
-100.00 percent change
Interval -100.0 to -100.0
|
|
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
Interval -100.0 to -100.0
|
-100.00 percent change
Interval -100.0 to -100.0
|
|
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
Interval -100.0 to -47.78
|
-100.00 percent change
Interval -100.0 to -100.0
|
|
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
Interval -100.0 to -100.0
|
-100.00 percent change
Interval -100.0 to -100.0
|
|
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
Interval -100.0 to -100.0
|
-100.00 percent change
Interval -100.0 to -85.11
|
|
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
Interval -100.0 to -22.73
|
-84.47 percent change
Interval -100.0 to -48.94
|
|
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
Interval -100.0 to -100.0
|
-100.00 percent change
Interval -100.0 to -100.0
|
|
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
Interval -100.0 to -66.67
|
-100.00 percent change
Interval -100.0 to -100.0
|
Adverse Events
Rituximab Plus Atacicept
Serious events: 6 serious events
Other events: 17 other events
Deaths: 0 deaths
Rituximab Plus Placebo
Serious events: 2 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Rituximab Plus Atacicept
n=18 participants at risk
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.
|
Rituximab Plus Placebo
n=9 participants at risk
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.
|
|---|---|---|
|
Nervous system disorders
Transient ischaemic attack
|
5.6%
1/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Nervous system disorders
Demyelination
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Nervous system disorders
Nervous system disorder
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Nervous system disorders
Ruptured cerebral aneurysm
|
0.00%
0/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Cardiac disorders
Atrial fibrillation
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Cardiac disorders
Cardiac arrest
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Cardiac disorders
Ventricular fibrillation
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Musculoskeletal and connective tissue disorders
Arthropathy
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Injury, poisoning and procedural complications
Joint capsule rupture
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Injury, poisoning and procedural complications
Pelvic fracture
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Eye disorders
Visual impairment
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Immune system disorders
Drug hypersensitivity
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Infections and infestations
Gastroenteritis
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Glioma
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
Other adverse events
| Measure |
Rituximab Plus Atacicept
n=18 participants at risk
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.
|
Rituximab Plus Placebo
n=9 participants at risk
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.
|
|---|---|---|
|
Infections and infestations
Upper respiratory tract infection
|
16.7%
3/18 • Baseline up to Week 64
|
33.3%
3/9 • Baseline up to Week 64
|
|
Infections and infestations
Influenza
|
11.1%
2/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Infections and infestations
Rhinitis
|
11.1%
2/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Infections and infestations
Urinary tract infection
|
5.6%
1/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Infections and infestations
Viral upper respiratory tract infection
|
5.6%
1/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Infections and infestations
Nasopharyngitis
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Infections and infestations
Herpes virus infection
|
0.00%
0/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Infections and infestations
Conjunctivitis viral
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Infections and infestations
Cystitis
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Infections and infestations
Fungal skin infection
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Infections and infestations
Herpes zoster
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Infections and infestations
Hordeolum
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Infections and infestations
Lower respiratory tract infection
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Infections and infestations
Pharyngitis
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
General disorders
Injection site reaction
|
38.9%
7/18 • Baseline up to Week 64
|
22.2%
2/9 • Baseline up to Week 64
|
|
General disorders
Injection site erythema
|
22.2%
4/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
General disorders
Injection site pruritus
|
22.2%
4/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
General disorders
Injection site swelling
|
11.1%
2/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
General disorders
Fatigue
|
5.6%
1/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
General disorders
Pyrexia
|
5.6%
1/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
General disorders
Injection site pain
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
General disorders
Asthenia
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
General disorders
Device dislocation
|
0.00%
0/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
General disorders
Injection site irritation
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
General disorders
Mucosal inflammation
|
0.00%
0/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
General disorders
Oedema peripheral
|
0.00%
0/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
16.7%
3/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
11.1%
2/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
11.1%
2/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Musculoskeletal and connective tissue disorders
Foot deformity
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Musculoskeletal and connective tissue disorders
Myopathy
|
0.00%
0/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Musculoskeletal and connective tissue disorders
Osteoporosis
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Musculoskeletal and connective tissue disorders
Plantar fasciitis
|
0.00%
0/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid nodule
|
0.00%
0/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
16.7%
3/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Skin and subcutaneous tissue disorders
Rash
|
11.1%
2/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
11.1%
2/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Skin and subcutaneous tissue disorders
Eczema
|
5.6%
1/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Skin and subcutaneous tissue disorders
Drug eruption
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Skin and subcutaneous tissue disorders
Increased tendency to bruise
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Skin and subcutaneous tissue disorders
Pruritus generalised
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Skin and subcutaneous tissue disorders
Rosacea
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
0.00%
0/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Skin and subcutaneous tissue disorders
Skin nodule
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Gastrointestinal disorders
Diarrhoea
|
11.1%
2/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Gastrointestinal disorders
Abdominal pain
|
11.1%
2/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Gastrointestinal disorders
Dry mouth
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Gastrointestinal disorders
Nausea
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Gastrointestinal disorders
Enteritis
|
0.00%
0/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Gastrointestinal disorders
Gastritis
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Gastrointestinal disorders
Glossodynia
|
0.00%
0/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Gastrointestinal disorders
Irritable bowel syndrome
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Gastrointestinal disorders
Mouth ulceration
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Gastrointestinal disorders
Vomiting
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Nervous system disorders
Headache
|
22.2%
4/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Nervous system disorders
Dizziness
|
11.1%
2/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Nervous system disorders
Brain oedema
|
0.00%
0/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Nervous system disorders
Migraine
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Nervous system disorders
Presyncope
|
0.00%
0/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Nervous system disorders
Subarachnoid haemorrhage
|
0.00%
0/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.6%
1/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
5.6%
1/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal blistering
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Eye disorders
Cataract
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Eye disorders
Dry eye
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Eye disorders
Eye pruritus
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Eye disorders
Vision blurred
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Immune system disorders
Drug hypersensitivity
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Immune system disorders
Food allergy
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Immune system disorders
Type I hypersensitivity
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Vascular disorders
Arteriosclerosis
|
0.00%
0/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Vascular disorders
Hot flush
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Vascular disorders
Hypertension
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Blood and lymphatic system disorders
Hypochromic anaemia
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Blood and lymphatic system disorders
Spontaneous haematoma
|
0.00%
0/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Injury, poisoning and procedural complications
Fall
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Injury, poisoning and procedural complications
Overdose
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Injury, poisoning and procedural complications
Wound
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Reproductive system and breast disorders
Breast mass
|
0.00%
0/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Reproductive system and breast disorders
Genital haemorrhage
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Cardiac disorders
Tachycardia
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Investigations
Weight increased
|
0.00%
0/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Metabolism and nutrition disorders
Gout
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign bone neoplasm
|
0.00%
0/18 • Baseline up to Week 64
|
11.1%
1/9 • Baseline up to Week 64
|
|
Psychiatric disorders
Insomnia
|
5.6%
1/18 • Baseline up to Week 64
|
0.00%
0/9 • Baseline up to Week 64
|
Additional Information
Merck KGaA Communication Center
Merck Serono, a division of Merck KGaA
Phone: +49-6151-72-5200
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Prior to publishing results, Institution and Principal Investigator (PI) must first provide Sponsor with a copy of proposed publication for review at least 30 days prior to submission. If Institution and PI do not agree to modification, they shall so notify Sponsor and postpone submission for additional 60 days to allow Sponsor to seek legal remedies or file patent applications. There is a need for coordinated approach to any publication of results from sites for any multi-site study.
- Publication restrictions are in place
Restriction type: OTHER