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A Study of Rituximab (MabThera®/Rituxan®) in Patients With Rheumatoid Arthritis and Inadequate Response to Methotrexate (SCORE)

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ClinicalTrials.gov Identifier: NCT00578305
Recruitment Status : Completed
First Posted : December 21, 2007
Results First Posted : April 10, 2015
Last Update Posted : April 10, 2015
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Biological: Rituximab
Drug: Placebo
Drug: Methylprednisolone
Drug: Methotrexate
Drug: Folic acid or folate
Enrollment 185
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Rituximab 500 mg Rituximab 1000 mg Placebo
Hide Arm/Group Description Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally. Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally. Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Period Title: Double-blind Treatment Phase
Started 62 60 63
Treated 62 60 63
Completed 59 56 49
Not Completed 3 4 14
Period Title: Extension Phase
Started 53 50 43
Completed 49 [1] 49 [1] 40 [1]
Not Completed 4 1 3
[1]
Some participants completed the study in this period and did not enter the safety follow-up period.
Period Title: Safety Follow-up Phase
Started 57 [1] 54 [1] 54 [1]
Completed 11 9 8
Not Completed 46 45 46
[1]
Some participants entered safety follow-up directly from the double-blind treatment period.
Arm/Group Title Rituximab 500 mg Rituximab 1000 mg Placebo Total
Hide Arm/Group Description Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally. Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally. Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally. Total of all reporting groups
Overall Number of Baseline Participants 62 60 63 185
Hide Baseline Analysis Population Description
Safety population: All participants who received any part of an infusion of the study drug during the main study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 62 participants 60 participants 63 participants 185 participants
48.7  (11.10) 50.7  (11.65) 50.3  (11.94) 49.9  (11.54)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 62 participants 60 participants 63 participants 185 participants
Female
45
  72.6%
50
  83.3%
48
  76.2%
143
  77.3%
Male
17
  27.4%
10
  16.7%
15
  23.8%
42
  22.7%
1.Primary Outcome
Title Change in Magnetic Resonance Imaging (MRI) Erosion Score From Baseline to Week 24
Hide Description The erosion score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI scoring (RAMRIS) system in magnetic resonance images with and without gadolinium of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists. Each location was scored in 0.5 increments from 0 to 10 with each integer unit increment representing a 10% loss of articular bone using the following scale. 0.0=normal, no erosion; 0.5=1-5% erosion; 1.0=6-10% erosion; 1.5=11-15% erosion; 2.0=16-20% erosion; etc, up to 10.0=96-100% erosion. The individual scores were summed and normalized to a range of 0 to 100 with a higher score indicating more erosion. A negative change score indicates improvement.
Time Frame Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
Arm/Group Title Rituximab 500 mg Rituximab 1000 mg Placebo
Hide Arm/Group Description:
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Overall Number of Participants Analyzed 59 58 60
Mean (Standard Deviation)
Unit of Measure: Units on a scale
0.13  (2.258) 0.39  (1.807) 1.33  (2.235)
2.Secondary Outcome
Title Change in Magnetic Resonance Imaging (MRI) Erosion Score From Baseline to Weeks 12 and 52
Hide Description The erosion score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI scoring (RAMRIS) system in magnetic resonance images with and without gadolinium of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists. Each location was scored in 0.5 increments from 0 to 10 with each integer unit increment representing a 10% loss of articular bone using the following scale. 0.0=normal, no erosion; 0.5=1-5% erosion; 1.0=6-10% erosion; 1.5=11-15% erosion; 2.0=16-20% erosion; etc, up to 10.0=96-100% erosion. The individual scores were summed and normalized to a range of 0 to 100 with a higher score indicating more erosion. A negative change score indicates improvement.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
Arm/Group Title Rituximab 500 mg Rituximab 1000 mg Placebo
Hide Arm/Group Description:
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Overall Number of Participants Analyzed 60 62 63
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Week 12 (n = 58, 58, 56) 0.42  (1.693) 0.13  (1.764) 0.33  (4.122)
Week 52 (n = 56, 57, 58) 0.11  (2.623) -0.30  (2.372) 3.02  (4.456)
3.Secondary Outcome
Title Change in Magnetic Resonance Imaging (MRI) Synovitis Score From Baseline to Weeks 12, 24, and Week 52
Hide Description The synovitis score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI scoring (RAMRIS) system in magnetic resonance images of 3 wrist regions and 5 metacarpophalangeal joints in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists. Each location was scored in 0.5 increments from 0 to 3 with each integer unit increment representing a 33% enhancement of the maximum volume of enhancing tissue in the synovial compartment using the following scale: 0.0=normal, no synovitis; 0.5=1-17% estimated volume of enhancement; 1.0=18-33%; 1.5=34-50%; 2.0=51-67%; 2.5=68-83%; 3.0=84-100% estimated volume of enhancement. The individual scores were summed and normalized to a range of 0 to 100 with a higher score indicating more synovitis. A negative change score indicates improvement.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
Arm/Group Title Rituximab 500 mg Rituximab 1000 mg Placebo
Hide Arm/Group Description:
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Overall Number of Participants Analyzed 62 60 63
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Week 12 (n = 58, 58, 56) -0.50  (1.701) -1.15  (1.866) -0.22  (2.050)
Week 24 (n = 61, 59, 59) -1.14  (1.923) -1.81  (2.289) 0.20  (2.257)
Week 52 (n = 61, 59, 59) -2.03  (2.562) -2.73  (3.120) -0.01  (2.700)
4.Secondary Outcome
Title Change in Magnetic Resonance Imaging (MRI) Osteitis Score From Baseline to Weeks 12, 24, and Week 52
Hide Description The osteitis score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI scoring (RAMRIS) system in magnetic resonance images of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Each location was scored in 0.5 increments from 0 to 3 with each integer unit increment representing a 33% increase in the volume of the peripheral 1 cm of original (eroded + residual) articular bone using the following scale: 0.0=normal, no osteitis; 0.5=1-17% involvement of original articular bone; 1.0=18-33%; 1.5=34-50%; 2.0=51-67%; 2.5=68-83%; 3.0=84-100% involvement of original articular bone. The individual scores were summed and normalized to a range of 0 to 100 with a higher score indicating more synovitis. A negative change score indicates improvement.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
Arm/Group Title Rituximab 500 mg Rituximab 1000 mg Placebo
Hide Arm/Group Description:
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Overall Number of Participants Analyzed 62 60 63
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Week 12 (n = 58, 58, 56) -2.11  (5.049) -1.88  (5.366) -0.14  (3.940)
Week 24 (n = 61, 59, 59) -2.91  (5.687) -2.86  (5.976) 0.07  (5.574)
Week 52 (n = 61, 59, 59) -4.75  (7.413) -3.83  (6.255) -0.22  (6.390)
5.Secondary Outcome
Title Percentage of Participants With no Newly Eroded Joints at Weeks 24 and 52
Hide Description No newly eroded joints was defined as no new erosions in joints which were scored 0 at baseline. The erosion score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI scoring (RAMRIS) system in magnetic resonance images with and without gadolinium of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists. Each location was scored in 0.5 increments from 0 to 10 with each integer unit increment representing a 10% loss of articular bone using the following scale. 0.0=normal, no erosion; 0.5=1-5% erosion; 1.0=6-10% erosion; 1.5=11-15% erosion; 2.0=16-20% erosion; etc, up to 10.0=96-100% erosion.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
Arm/Group Title Rituximab 500 mg Rituximab 1000 mg Placebo
Hide Arm/Group Description:
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Overall Number of Participants Analyzed 62 60 63
Measure Type: Number
Unit of Measure: Percentage of participants
Week 24 77.4 73.3 55.5
Week 52 77.4 40 60.3
6.Secondary Outcome
Title Percentage of Participants With no Progression/no Worsening in Bone Erosion at Weeks 24 and 52
Hide Description There were 2 definitions of no progression/no worsening in bone erosion. A participant met the criterion for definition 1 when there was a change in the magnetic resonance imaging erosion score ≤ 0. A participant met the criteria for definition 2 when there was either (1) no change from Baseline in the MRI erosion score, (2) an increase in erosion score and the size of the increase in score was smaller than the smallest detectable change, or (3) a drop in the erosion score. The erosion score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI scoring (RAMRIS) system in magnetic resonance images with and without gadolinium of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
Arm/Group Title Rituximab 500 mg Rituximab 1000 mg Placebo
Hide Arm/Group Description:
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Overall Number of Participants Analyzed 62 60 63
Measure Type: Number
Unit of Measure: Percentage of participants
Week 24 (Definition 1) 50.0 51.7 33.3
Week 24 (Definition 2) 88.7 96.7 81.0
Week 52 (Definition 1) 48.4 55.0 27.0
Week 52 (Definition 2) 85.5 93.3 55.6
7.Secondary Outcome
Title Percentage of Participants With Improvement in Synovitis at Weeks 24 and 52
Hide Description There were 2 definitions of improvement in synovitis. A participant met the criterion for definition 1 when there was a drop in the magnetic resonance imaging synovitis score from Baseline > 0.5. A participant met the criterion for definition 2 when there was a drop in the magnetic resonance imaging synovitis score from Baseline > than the smallest detectable change. The synovitis score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI (RAMRIS) scoring system in magnetic resonance images with and without gadolinium of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
Arm/Group Title Rituximab 500 mg Rituximab 1000 mg Placebo
Hide Arm/Group Description:
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Overall Number of Participants Analyzed 62 60 63
Measure Type: Number
Unit of Measure: Percentage of participants
Week 24 (Definition 1) 41.9 56.7 22.2
Week 24 (Definition 2) 41.9 56.7 22.2
Week 52 (Definition 1) 54.8 60.0 25.4
Week 52 (Definition 2) 54.8 60.0 25.4
8.Secondary Outcome
Title Percentage of Participants With Improvement in Osteitis at Weeks 24 and 52
Hide Description There were 2 definitions of improvement in osteitis. A participant met the criterion for definition 1 when there was a drop in the magnetic resonance imaging osteitis score from Baseline > 0.5. A participant met the criterion for definition 2 when there was a drop in the magnetic resonance imaging osteitis score from Baseline > than the smallest detectable change. The osteitis score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI (RAMRIS) scoring system in magnetic resonance images with and without gadolinium of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
Arm/Group Title Rituximab 500 mg Rituximab 1000 mg Placebo
Hide Arm/Group Description:
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Overall Number of Participants Analyzed 62 60 63
Measure Type: Number
Unit of Measure: Percentage of participants
Week 24 (Definition 1) 50.0 51.7 22.2
Week 24 (Definition 2) 50.0 51.7 22.2
Week 52 (Definition 1) 58.1 51.7 27.0
Week 52 (Definition 2) 58.1 51.7 27.0
9.Secondary Outcome
Title Change From Baseline in the Disease Activity Score 28 (DAS28) at Weeks 24 and 52
Hide Description The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, C-reactive protein level (CRP), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(CRO)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints, GH = a participant's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity [symptom-free and no arthritis symptoms], right end = maximum disease activity [maximum arthritis disease activity]). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A negative change score indicates improvement.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
Arm/Group Title Rituximab 500 mg Rituximab 1000 mg Placebo
Hide Arm/Group Description:
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Overall Number of Participants Analyzed 62 60 63
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Week 24 (n = 63, 62, 59) -1.714  (1.2204) -1.683  (1.0158) -0.752  (1.1834)
Week 52 (n = 63, 62, 59) -2.055  (1.1844) -1.801  (1.0443) -0.747  (1.2557)
10.Secondary Outcome
Title Percentage of Participants With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 24 and 52
Hide Description Change of the DAS28 score from Baseline was used to determine the EULAR responses. For a post-Baseline score ≤ 3.2, a change from Baseline of < -1.2 was a good response, < -0.6 to ≥ -1.2 was a moderate response, and ≥ -0.6 was no response. For a post-Baseline score > 3.2 to ≤ 5.1, a change from Baseline of < -0.6 was a moderate response and ≥ -0.6 was no response. For a post-Baseline score > 5.1, a change from Baseline < -1.2 was a moderate response and ≥ -1.2 was no response. A good response could not be achieved for post-Baseline scores > 3.2. DAS28=(0.56×√(TJC28))+(0.28×√(SJC28))+(0.7×log(CRP))+(0.014×GH), where TJC28=tender joint count (JC) and SJC28=swollen JC (28 joints), GH=a participant's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end=no disease activity, right end=maximum disease activity), and CRP=C-reactive protein level. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
Arm/Group Title Rituximab 500 mg Rituximab 1000 mg Placebo
Hide Arm/Group Description:
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Overall Number of Participants Analyzed 62 60 63
Measure Type: Number
Unit of Measure: Percentage of participants
Week 24 - No response 33.9 22.0 58.7
Week 24 - Moderate response 37.1 42.4 22.2
Week 24 - Good response 29.0 35.6 19.0
Week 52 (n = 63, 62, 59) - No response 21.0 13.6 60.3
Week 52 (n = 63, 62, 59) - Moderate response 45.2 49.2 31.7
Week 52 (n = 63, 62, 59) - Good response 33.9 37.3 7.9
11.Secondary Outcome
Title Percentage of Participants With Low Disease Activity (Disease Activity Score 28 [DAS28] ≤ 3.2) at Weeks 24 and 52
Hide Description The percentage of participants who had low rheumatic arthritis disease activity at Weeks 24 and 52, as measured by a DAS28 score ≤ 3.2, is reported. DAS28 is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(CRO)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints, GH = a participant's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity [symptom-free and no arthritis symptoms], right end = maximum disease activity [maximum arthritis disease activity]), and CRP = C-reactive protein level. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
Arm/Group Title Rituximab 500 mg Rituximab 1000 mg Placebo
Hide Arm/Group Description:
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Overall Number of Participants Analyzed 62 60 63
Measure Type: Number
Unit of Measure: Percentage of participants
Week 24 33.9 36.7 19.0
Week 52 37.1 38.3 9.5
12.Secondary Outcome
Title Percentage of Participants in Remission Response (Disease Activity Score 28 [DAS28] < 2.6) at Weeks 24 and 52
Hide Description The percentage of participants in remission of their rheumatic arthritis at Weeks 24 and 52, as measured by a DAS28 score < 2.6, is reported. DAS28 is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(CRO)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints, GH = a participant's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity [symptom-free and no arthritis symptoms], right end = maximum disease activity [maximum arthritis disease activity]), and CRP = C-reactive protein level. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
Arm/Group Title Rituximab 500 mg Rituximab 1000 mg Placebo
Hide Arm/Group Description:
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Overall Number of Participants Analyzed 62 60 63
Measure Type: Number
Unit of Measure: Percentage of participants
Week 24 21.0 28.3 12.7
Week 52 25.8 25.0 7.9
13.Secondary Outcome
Title Percentage of Participants With an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Weeks 24 and 52
Hide Description Improvement must be seen in tender and swollen joint counts (28 assessed joints; Joints were evaluated and classified as swollen or not swollen and tender or not tender based on pressure and joint manipulation upon physical examination) and in at least 3
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
Arm/Group Title Rituximab 500 mg Rituximab 1000 mg Placebo
Hide Arm/Group Description:
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Overall Number of Participants Analyzed 62 60 63
Measure Type: Number
Unit of Measure: Percentage of participants
Week 24 - ACR20 response 51.6 51.7 28.6
Week 24 - ACR50 response 24.2 26.7 11.1
Week 24 - ACR70 response 11.3 8.3 1.6
Week 52 - ACR20 response 67.7 68.3 28.6
Week 52 - ACR50 response 37.1 35.0 14.3
Week 52 - ACR70 response 17.7 16.7 6.3
14.Secondary Outcome
Title Percentage of Participants Achieving a Major Clinical Response at Week 52
Hide Description A major clinical response was defined as an improvement of at least 70% in the American College of Rheumatology score from Baseline at Week 52. Improvement must be seen in tender and swollen joint counts (28 assessed joints) and in at least 3 of the following 5 parameters: Separate participant and physician assessments of participant disease activity in the previous 24 hours on a visual analog scale (VAS, the extreme left end of the line "no disease activity" [symptom-free and no arthritis symptoms] and the extreme right end "maximum disease activity"); participant assessment of pain in previous the 24 hours on a VAS (extreme left end of the line "no pain" and the extreme right end "unbearable pain"); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and C reactive protein level.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
Arm/Group Title Rituximab 500 mg Rituximab 1000 mg Placebo
Hide Arm/Group Description:
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Overall Number of Participants Analyzed 62 60 63
Measure Type: Number
Unit of Measure: Percentage of participants
6.5 6.7 1.6
15.Secondary Outcome
Title Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Hide Description Correlation coefficients of magnetic resonance imaging erosion, synovitis, and osteitis scores and clinical outcome measures of swollen joint count (SJC), tender joint count (TJC), C-reactive protein level (CRP), erythrocyte sedimentation rate (ESR), a participant's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (GH), Disease Activity Score 28-C-reactive protein (DAS28-CRP), and Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) are reported. Not all of these variables were specified as primary or secondary Outcome Measures in the study protocol and were not individually analyzed.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
Arm/Group Title Rituximab 500 mg Rituximab 1000 mg Placebo
Hide Arm/Group Description:
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Overall Number of Participants Analyzed 62 60 63
Measure Type: Number
Unit of Measure: Correlation coefficient
Erosion score and SJC - Week 24 0.341 0.425 0.446
Erosion score and SJC - Week 52 0.287 0.234 0.355
Synovitis score and SJC - Week 24 0.329 0.389 0.566
Synovitis score and SJC - Week 52 0.168 0.188 0.574
Osteitis score and SJC - Week 24 0.407 0.354 0.370
Osteitis score and SJC - Week 52 0.265 0.192 0.398
Erosion score and TJC - Week 24 0.364 0.115 0.298
Erosion score and TJC - Week 52 0.275 0.067 0.425
Synovitis score and TJC - Week 24 0.336 0.174 0.282
Synovitis score and TJC - Week 52 0.142 0.036 0.421
Osteitis score and TJC - Week 24 0.355 0.118 0.288
Osteitis score and TJC - Week 52 0.245 0.048 0.371
Erosion score and CRP - Week 24 0.185 -0.024 0.006
Erosion score and CRP - Week 52 0.055 0.098 0.352
Synovitis score and CRP - Week 24 0.030 0.090 0.192
Synovitis score and CRP - Week 52 -0.077 0.085 0.311
Osteitis score and CRP - Week 24 -0.031 -0.057 0.040
Osteitis score and CRP - Week 52 0.005 -0.010 0.119
Erosion score and ESR - Week 24 0.321 0.136 0.197
Erosion score and ESR - Week 52 0.127 0.188 0.314
Synovitis score and ESR - Week 24 0.182 0.214 0.358
Synovitis score and ESR - Week 52 0.185 0.248 0.360
Osteitis score and ESR - Week 24 0.044 0.043 0.148
Osteitis score and ESR - Week 52 -0.041 0.116 0.205
Erosion score and GH - Week 24 0.206 0.043 0.326
Erosion score and GH - Week 52 0.063 -0.009 0.316
Synovitis score and GH - Week 24 0.186 0.221 0.206
Synovitis score and GH - Week 52 -0.026 -0.037 0.286
Osteitis score and GH - Week 24 0.274 0.122 0.205
Osteitis score and GH - Week 52 0.106 0.052 0.136
Erosion score and DAS28-CRP - Week 24 0.420 0.198 0.457
Erosion score and DAS28-CRP - Week 52 0.238 0.127 0.498
Synovitis score and DAS28-CRP - Week 24 0.393 0.349 0.437
Synovitis score and DAS28-CRP - Week 52 0.149 0.150 0.500
Osteitis score and DAS28-CRP - Week 24 0.380 0.209 0.351
Osteitis score and DAS28-CRP - Week 52 0.139 0.143 0.356
Erosion score and DAS28-ESR - Week 24 0.429 0.255 0.439
Erosion score and DAS28-ESR - Week 52 0.244 0.180 0.473
Synovitis score and DAS28-ESR - Week 24 0.398 0.332 0.438
Synovitis score and DAS28-ESR - Week 52 0.198 0.147 0.514
Osteitis score and DAS28-ESR - Week 24 0.353 0.231 0.353
Osteitis score and DAS28-ESR - Week 52 0.108 0.172 0.356
16.Secondary Outcome
Title Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 24 and 52
Hide Description The HAQ-DI assesses how well the patient is able to perform 8 activities: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. The patient answers 20 questions with 1 of 4 responses with the past week as the time frame: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. The highest score for any question in a category determines the category score. The total score ranges from 0 (no disability) to 3 (completely disabled). A negative change score indicates improvement.
Time Frame Baseline to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
Arm/Group Title Rituximab 500 mg Rituximab 1000 mg Placebo
Hide Arm/Group Description:
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Overall Number of Participants Analyzed 62 60 63
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Week 24 (n = 63, 62, 59) -0.425  (0.5606) -0.439  (0.4770) -0.194  (0.5849)
Week 52 (n = 63, 62, 59) -0.520  (0.5873) -0.417  (0.4450) -0.177  (0.5943)
17.Secondary Outcome
Title Adverse Events (AEs), Laboratory Parameters, C-reactive Protein, ESR.
Hide Description [Not Specified]
Time Frame Throughout study
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description

Safety population: All participants who received any part of an infusion of the study drug during the main study.

Some participants entered the safety follow-up period directly from the double-blind treatment period.

 
Arm/Group Title Rituximab 500 mg - Double-blind Treatment Phase Rituximab 1000 mg - Double-blind Treatment Phase Placebo - Double-blind Treatment Phase Rituximab 500 mg - Extension Phase Rituximab 1000 mg - Extension Phase Placebo - Extension Phase Rituximab 500 mg - Safety Follow-up Phase Rituximab 1000 mg - Safety Follow-up Phase Placebo - Safety Follow-up Phase
Hide Arm/Group Description Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally. Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally. Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally. Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally. Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally. Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally. Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally. Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally. Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
All-Cause Mortality
Rituximab 500 mg - Double-blind Treatment Phase Rituximab 1000 mg - Double-blind Treatment Phase Placebo - Double-blind Treatment Phase Rituximab 500 mg - Extension Phase Rituximab 1000 mg - Extension Phase Placebo - Extension Phase Rituximab 500 mg - Safety Follow-up Phase Rituximab 1000 mg - Safety Follow-up Phase Placebo - Safety Follow-up Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Rituximab 500 mg - Double-blind Treatment Phase Rituximab 1000 mg - Double-blind Treatment Phase Placebo - Double-blind Treatment Phase Rituximab 500 mg - Extension Phase Rituximab 1000 mg - Extension Phase Placebo - Extension Phase Rituximab 500 mg - Safety Follow-up Phase Rituximab 1000 mg - Safety Follow-up Phase Placebo - Safety Follow-up Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/62 (4.84%)   4/60 (6.67%)   5/63 (7.94%)   3/50 (6.00%)   5/47 (10.64%)   2/41 (4.88%)   0/57 (0.00%)   1/54 (1.85%)   0/54 (0.00%) 
Blood and lymphatic system disorders                   
Neutropenia  1  0/62 (0.00%)  0/60 (0.00%)  0/63 (0.00%)  1/50 (2.00%)  0/47 (0.00%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Cardiac disorders                   
Acute coronary syndrome  1  0/62 (0.00%)  0/60 (0.00%)  1/63 (1.59%)  0/50 (0.00%)  0/47 (0.00%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Gastrointestinal disorders                   
Colonic polyp  1  0/62 (0.00%)  0/60 (0.00%)  1/63 (1.59%)  0/50 (0.00%)  0/47 (0.00%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Intestinal diverticulum  1  0/62 (0.00%)  0/60 (0.00%)  1/63 (1.59%)  0/50 (0.00%)  0/47 (0.00%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
General disorders                   
General physical health deterioration  1  0/62 (0.00%)  0/60 (0.00%)  1/63 (1.59%)  0/50 (0.00%)  0/47 (0.00%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Hepatobiliary disorders                   
Cholecystitis acute  1  0/62 (0.00%)  0/60 (0.00%)  0/63 (0.00%)  0/50 (0.00%)  0/47 (0.00%)  1/41 (2.44%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Cholelithiasis  1  0/62 (0.00%)  0/60 (0.00%)  0/63 (0.00%)  0/50 (0.00%)  0/47 (0.00%)  1/41 (2.44%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Infections and infestations                   
Bronchitis  1  0/62 (0.00%)  1/60 (1.67%)  0/63 (0.00%)  0/50 (0.00%)  0/47 (0.00%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Omphalitis  1  0/62 (0.00%)  1/60 (1.67%)  0/63 (0.00%)  0/50 (0.00%)  0/47 (0.00%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Soft tissue infection  1  1/62 (1.61%)  0/60 (0.00%)  0/63 (0.00%)  0/50 (0.00%)  0/47 (0.00%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Appendicitis  1  0/62 (0.00%)  0/60 (0.00%)  0/63 (0.00%)  1/50 (2.00%)  0/47 (0.00%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Erysipelas  1  0/62 (0.00%)  0/60 (0.00%)  0/63 (0.00%)  0/50 (0.00%)  0/47 (0.00%)  1/41 (2.44%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Respiratory tract infection viral  1  0/62 (0.00%)  0/60 (0.00%)  0/63 (0.00%)  0/50 (0.00%)  1/47 (2.13%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Metabolism and nutrition disorders                   
Hyperglycemia  1  1/62 (1.61%)  0/60 (0.00%)  0/63 (0.00%)  0/50 (0.00%)  0/47 (0.00%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Musculoskeletal and connective tissue disorders                   
Rheumatoid arthritis  1  0/62 (0.00%)  0/60 (0.00%)  2/63 (3.17%)  0/50 (0.00%)  0/47 (0.00%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Back pain  1  0/62 (0.00%)  0/60 (0.00%)  0/63 (0.00%)  0/50 (0.00%)  1/47 (2.13%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Knee deformity  1  0/62 (0.00%)  0/60 (0.00%)  0/63 (0.00%)  0/50 (0.00%)  1/47 (2.13%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                   
Papillary serous endometrial carcinoma  1  0/62 (0.00%)  1/60 (1.67%)  0/63 (0.00%)  0/50 (0.00%)  0/47 (0.00%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Colorectal cancer  1  0/62 (0.00%)  0/60 (0.00%)  0/63 (0.00%)  0/50 (0.00%)  1/47 (2.13%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Prostate cancer  1  0/62 (0.00%)  0/60 (0.00%)  0/63 (0.00%)  0/50 (0.00%)  1/47 (2.13%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Cervix carcinoma Stage 0  1  0/62 (0.00%)  0/60 (0.00%)  0/63 (0.00%)  0/50 (0.00%)  0/47 (0.00%)  0/41 (0.00%)  0/57 (0.00%)  1/54 (1.85%)  0/54 (0.00%) 
Nervous system disorders                   
Lumbar radiculopathy  1  0/62 (0.00%)  0/60 (0.00%)  0/63 (0.00%)  1/50 (2.00%)  0/47 (0.00%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Pregnancy, puerperium and perinatal conditions                   
Omphalorrhexis  1  0/62 (0.00%)  1/60 (1.67%)  0/63 (0.00%)  0/50 (0.00%)  0/47 (0.00%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Renal and urinary disorders                   
Renal colic  1  1/62 (1.61%)  0/60 (0.00%)  0/63 (0.00%)  0/50 (0.00%)  0/47 (0.00%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Reproductive system and breast disorders                   
Breast mass  1  0/62 (0.00%)  0/60 (0.00%)  0/63 (0.00%)  0/50 (0.00%)  1/47 (2.13%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Respiratory, thoracic and mediastinal disorders                   
Bronchitis chronic  1  0/62 (0.00%)  1/60 (1.67%)  0/63 (0.00%)  0/50 (0.00%)  0/47 (0.00%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (11.2)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Rituximab 500 mg - Double-blind Treatment Phase Rituximab 1000 mg - Double-blind Treatment Phase Placebo - Double-blind Treatment Phase Rituximab 500 mg - Extension Phase Rituximab 1000 mg - Extension Phase Placebo - Extension Phase Rituximab 500 mg - Safety Follow-up Phase Rituximab 1000 mg - Safety Follow-up Phase Placebo - Safety Follow-up Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   24/62 (38.71%)   24/60 (40.00%)   20/63 (31.75%)   0/50 (0.00%)   0/47 (0.00%)   0/41 (0.00%)   0/57 (0.00%)   0/54 (0.00%)   0/54 (0.00%) 
Immune system disorders                   
Rheumatoid arthritis  1  2/62 (3.23%)  1/60 (1.67%)  6/63 (9.52%)  0/50 (0.00%)  0/47 (0.00%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Infections and infestations                   
Bronchitis  1  4/62 (6.45%)  5/60 (8.33%)  2/63 (3.17%)  0/50 (0.00%)  0/47 (0.00%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Oral herpes  1  1/62 (1.61%)  3/60 (5.00%)  0/63 (0.00%)  0/50 (0.00%)  0/47 (0.00%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Viral infection  1  4/62 (6.45%)  3/60 (5.00%)  2/63 (3.17%)  0/50 (0.00%)  0/47 (0.00%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Musculoskeletal and connective tissue disorders                   
Arthralgia  1  4/62 (6.45%)  0/60 (0.00%)  1/63 (1.59%)  0/50 (0.00%)  0/47 (0.00%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Back pain  1  1/62 (1.61%)  4/60 (6.67%)  1/63 (1.59%)  0/50 (0.00%)  0/47 (0.00%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Nervous system disorders                   
Headache  1  4/62 (6.45%)  0/60 (0.00%)  1/63 (1.59%)  0/50 (0.00%)  0/47 (0.00%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Respiratory, thoracic and mediastinal disorders                   
Nasopharyngitis  1  2/62 (3.23%)  3/60 (5.00%)  2/63 (3.17%)  0/50 (0.00%)  0/47 (0.00%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Upper respiratory tract infection  1  2/62 (3.23%)  4/60 (6.67%)  1/63 (1.59%)  0/50 (0.00%)  0/47 (0.00%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Vascular disorders                   
Hypertension  1  0/62 (0.00%)  1/60 (1.67%)  4/63 (6.35%)  0/50 (0.00%)  0/47 (0.00%)  0/41 (0.00%)  0/57 (0.00%)  0/54 (0.00%)  0/54 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (11.2)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800 821-8590
EMail: genentech@druginfo.com
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00578305    
Other Study ID Numbers: MA21056
First Submitted: December 19, 2007
First Posted: December 21, 2007
Results First Submitted: February 19, 2015
Results First Posted: April 10, 2015
Last Update Posted: April 10, 2015