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A Study of the Safety and Efficacy of Rituximab in Patients With Moderate to Severe Rheumatoid Arthritis Receiving Methotrexate (RUMBA)

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ClinicalTrials.gov Identifier: NCT00243412
Recruitment Status : Completed
First Posted : October 24, 2005
Results First Posted : October 7, 2011
Last Update Posted : October 7, 2011
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Drug: folate
Drug: methotrexate
Drug: methylprednisolone
Drug: Placebo
Drug: Rituximab
Enrollment 42
Recruitment Details Approximately 40 subjects with moderately to severely active rheumatoid arthritis were to be enrolled at six to eight study centers in the United States and were randomly assigned in a 1:1 ratio to Arm A or B. Starting 15 August 2005 to 4 February 2009 (first subject enrolled to database lock).
Pre-assignment Details All subjects were to receive rituximab 1000 mg * 2 on Days 1 and 15. Subsequently, subjects in Arm A received rituximab 500 mg * 2 every 6 months (Months 6, 12, and 18) and those in Arm B received rituximab 1000 mg * 2 at 12 months. To maintain the blind, subjects in Arm B received placebo infusions at Months 6 and 18.
Arm/Group Title Arm A: 500 mg Rituximab Arm B: 1000 mg Rituximab
Hide Arm/Group Description Rituximab: 1000 mg intravenous (IV) on Days 1 and 15 of the first cycle; 500 mg IV on Days 1 and 15 of each subsequent 6-month cycle (Months 6, 12, and 18). Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. Methotrexate: 15–25 mg/wk oral or parenteral (10–14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk). Rituximab: 1000 mg IV on Days 1 and 15 of each 12-month cycle (Rituximab cycles were administered at baseline and Month 12). For the Month 6 and 18 cycles, rituximab or placebo was administered. Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion, For the Months 6 and 18 cycles, IV saline was administered prior to each rituximab or placebo infusion. Methotrexate: 15–25 mg/wk oral or parenteral (10–14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Period Title: Overall Study
Started 21 [1] 21 [1]
Safety Evaluable 21 20
Completed 11 [2] 10 [2]
Not Completed 10 11
Reason Not Completed
Death             0             1
Adverse Event             4             2
Lost to Follow-up             0             1
Physician Decision             1             1
Withdrawal by Subject             4             5
not specified             1             1
[1]
Intent to treat
[2]
Completed Week 104
Arm/Group Title Arm A: 500 mg Rituximab Arm B: 1000 mg Rituximab Total
Hide Arm/Group Description Rituximab: 1000 mg IV on Days 1 and 15 of the first cycle; 500 mg IV on Days 1 and 15 of each subsequent 6-month cycle (Months 6, 12, and 18). Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. Methotrexate: 15–25 mg/wk oral or parenteral (10–14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk). Rituximab: 1000 mg IV on Days 1 and 15 of each 12-month cycle (Rituximab cycles were administered at baseline and Month 12). For the Month 6 and 18 cycles, rituximab or placebo was administered. Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. For the Months 6 and 18 cycles, IV saline was administered prior to each rituximab or placebo infusion. Methotrexate: 15–25 mg/wk oral or parenteral (10–14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk). Total of all reporting groups
Overall Number of Baseline Participants 21 21 42
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants 21 participants 42 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
21
 100.0%
20
  95.2%
41
  97.6%
>=65 years
0
   0.0%
1
   4.8%
1
   2.4%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 21 participants 21 participants 42 participants
46.9  (9.6) 47.4  (11.1) 47.2  (10.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants 21 participants 42 participants
Female
19
  90.5%
18
  85.7%
37
  88.1%
Male
2
   9.5%
3
  14.3%
5
  11.9%
1.Primary Outcome
Title Number of Participants With Either an Infection or a Grade III or IV Adverse Event (National Cancer Institute Common Toxicity Criteria for Adverse Events [NCI CTCAE], Version 3.0)
Hide Description

A Grade III Adverse Event (AE) is severe; defined as considerable interference with the subject’s daily activities, medical intervention/therapy required and hospitalization possible.

A Grade IV AE is life-threatening; defined as extreme limitation in activity, significant medical intervention/therapy required, hospitalization probable.

Because of the small sample size and the small number of subjects who completed Week 104, the analysis were limited to descriptive statistics only.

Time Frame 24 months
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Hide Analysis Population Description
Safety−Evaluable Population
Arm/Group Title Arm A: 500 mg Rituximab Arm B: 1000 mg Rituximab
Hide Arm/Group Description:
Rituximab: 1000 mg IV on Days 1 and 15 of the first cycle; 500 mg IV on Days 1 and 15 of each subsequent 6-month cycle (Months 6, 12, and 18). Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. Methotrexate: 15–25 mg/wk oral or parenteral (10–14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Rituximab: 1000 mg IV on Days 1 and 15 of each 12-month cycle (Rituximab cycles were administered at baseline and Month 12). For the Month 6 and 18 cycles, rituximab or placebo was administered. Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. For the Months 6 and 18 cycles, IV saline was administered prior to each rituximab or placebo infusion. Methotrexate: 15–25 mg/wk oral or parenteral (10–14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Overall Number of Participants Analyzed 21 20
Measure Type: Number
Unit of Measure: Participants
Infections 14 11
Adverse Events (Grade 3 or 4) 5 4
2.Secondary Outcome
Title Change From Baseline in Disease Activity Score 28-4 C-reactive Protein (DAS28-4(CRP))
Hide Description The DAS28-4(CRP) score is a measure of the subject’s disease activity. DAS28-4(CRP) is based on the tender joint count (28 joints), swollen joint count (28 joints), patient’s global assessment of disease activity and CRP. DAS28 provides a number on a scale (0 to 10) indicating current disease activity. A score above 5.1 means high disease activity and a score below 3.2 indicates low disease activity. Change from baseline at 24 months was analyzed for DAS28-4 (CRP).
Time Frame Baseline, 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Intent−to−Treat (ITT) population for whom data was available at baseline and month 24.
Arm/Group Title Arm A: 500 mg Rituximab Arm B: 1000 mg Rituximab
Hide Arm/Group Description:
Rituximab: 1000 mg IV on Days 1 and 15 of the first cycle; 500 mg IV on Days 1 and 15 of each subsequent 6-month cycle (Months 6, 12, and 18). Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. Methotrexate: 15–25 mg/wk oral or parenteral (10–14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Rituximab: 1000 mg IV on Days 1 and 15 of each 12-month cycle (Rituximab cycles were administered at baseline and Month 12). For the Month 6 and 18 cycles, rituximab or placebo was administered. Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. For the Months 6 and 18 cycles, IV saline was administered prior to each rituximab or placebo infusion. Methotrexate: 15–25 mg/wk oral or parenteral (10–14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Overall Number of Participants Analyzed 11 10
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Baseline 6.53  (0.70) 6.33  (0.85)
Month 24 4.03  (1.75) 3.77  (1.42)
Change from baseline -2.49  (1.85) -2.56  (1.23)
3.Secondary Outcome
Title Number of Participants With American College of Rheumatology Responses (ACR20, ACR50, and ACR70)
Hide Description

ACR20 response was defined as satisfying the following 3 criteria improvement from baseline: ≥ 20% in tender joint count; ≥ 20% in swollen joint count; ≥ 20% improvement from baseline in 3 of the following 5 criteria:

Subject’s Global Assessment of Pain Subject’s Global Assessment of Disease Activity Physician’s Global Assessment Subject’s Self-Assessment Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) Note: The definitions of ACR50 and ACR70 are the same as ACR20, except that the 20% value in the above definition is replaced by 50% and 70% values, respectively.

Time Frame Baseline, 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent−to−Treat (ITT)
Arm/Group Title Arm A: 500 mg Rituximab Arm B: 1000 mg Rituximab
Hide Arm/Group Description:
Rituximab: 1000 mg IV on Days 1 and 15 of the first cycle; 500 mg IV on Days 1 and 15 of each subsequent 6-month cycle (Months 6, 12, and 18). Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. Methotrexate: 15–25 mg/wk oral or parenteral (10–14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Rituximab: 1000 mg IV on Days 1 and 15 of each 12-month cycle (Rituximab cycles were administered at baseline and Month 12). For the Month 6 and 18 cycles, rituximab or placebo was administered. Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. For the Months 6 and 18 cycles, IV saline was administered prior to each rituximab or placebo infusion. Methotrexate: 15–25 mg/wk oral or parenteral (10–14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Overall Number of Participants Analyzed 21 21
Measure Type: Number
Unit of Measure: Participants
ACR20 Responders 7 6
ACR50 Responders 4 5
ACR70 Responders 4 3
4.Secondary Outcome
Title Number of Participants With American College of Rheumatology (ACR) Major Clinical Response and/or Remission
Hide Description

Major clinical response is an ACR70 response defined as improvement from baseline: ≥70% in tender joint count; ≥70% in swollen joint count; ≥70% in 3 of the following: Patient Pain Assessment, Patient Global Assessment, Physician Global Assessment, Patient Self-Assessed Disability, ESR or CRP for ≥169 consecutive days.

Remission: ≥5 requirements fulfilled for ≥2 consecutive months: Duration of morning stiffness <15 minutes, No fatigue, No joint pain, No joint tenderness or pain on motion, No soft tissue swelling in joints or tendon sheaths, ESR <30 mm/hour for women and <20 mm/hour for men.

Time Frame 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent−to−Treat (ITT)
Arm/Group Title Arm A: 500 mg Rituximab Arm B: 1000 mg Rituximab
Hide Arm/Group Description:
Rituximab: 1000 mg IV on Days 1 and 15 of the first cycle; 500 mg IV on Days 1 and 15 of each subsequent 6-month cycle (Months 6, 12, and 18). Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. Methotrexate: 15–25 mg/wk oral or parenteral (10–14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Rituximab: 1000 mg IV on Days 1 and 15 of each 12-month cycle (Rituximab cycles were administered at baseline and Month 12). For the Month 6 and 18 cycles, rituximab or placebo was administered. Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. For the Months 6 and 18 cycles, IV saline was administered prior to each rituximab or placebo infusion. Methotrexate: 15–25 mg/wk oral or parenteral (10–14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Overall Number of Participants Analyzed 21 20
Measure Type: Number
Unit of Measure: Participants
1 0
5.Secondary Outcome
Title Number of Participants With European League Against Rheumatism (EULAR) Response and Remission Using Disease Activity Score 28–4 (DAS28-4)C-reactive Protein (CRP)
Hide Description

EULAR remission = DAS28-4(CRP) < 2.6 (Fransen et al. 2004.

EULAR response categories (van Gestel et al. 1999):

Good response = final DAS28-4(CRP) < 3.2 and decreased > 1.2 points from baseline Moderate response = final DAS28-4(CRP) ≥ 3.2 but ≤ 5.1 and decreased > 0.6 points from baseline or final DAS28-4(CRP) > 5.1 and decreased > 1.2 from baseline.

Time Frame Baseline, 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Intent−to−Treat (ITT) population for whom data was available at baseline and month 24.
Arm/Group Title Arm A: 500 mg Rituximab Arm B: 1000 mg Rituximab
Hide Arm/Group Description:
Rituximab: 1000 mg IV on Days 1 and 15 of the first cycle; 500 mg IV on Days 1 and 15 of each subsequent 6-month cycle (Months 6, 12, and 18). Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. Methotrexate: 15–25 mg/wk oral or parenteral (10–14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Rituximab: 1000 mg IV on Days 1 and 15 of each 12-month cycle (Rituximab cycles were administered at baseline and Month 12). For the Month 6 and 18 cycles, rituximab or placebo was administered. Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. For the Months 6 and 18 cycles, IV saline was administered prior to each rituximab or placebo infusion. Methotrexate: 15–25 mg/wk oral or parenteral (10–14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Overall Number of Participants Analyzed 11 10
Measure Type: Number
Unit of Measure: Participants
No Response 0 0
Moderate Response 2 6
Good Response 5 4
Eular Remission 3 3
6.Secondary Outcome
Title Change From Baseline in Short Form 36 (SF 36) Summary and Subscale Scores
Hide Description The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning (PF), Role Physical (RP), Bodily Pain(BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE),Mental Health (MH). Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score.
Time Frame Baseline, 24 Months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Intent−to−Treat (ITT) for whom data was available at baseline and month 24.
Arm/Group Title Arm A: 500 mg Rituximab Arm B: 1000 mg Rituximab
Hide Arm/Group Description:
Rituximab: 1000 mg IV on Days 1 and 15 of the first cycle; 500 mg IV on Days 1 and 15 of each subsequent 6-month cycle (Months 6, 12, and 18). Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. Methotrexate: 15–25 mg/wk oral or parenteral (10–14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Rituximab: 1000 mg IV on Days 1 and 15 of each 12-month cycle (Rituximab cycles were administered at baseline and Month 12). For the Month 6 and 18 cycles, rituximab or placebo was administered. Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. For the Months 6 and 18 cycles, IV saline was administered prior to each rituximab or placebo infusion. Methotrexate: 15–25 mg/wk oral or parenteral (10–14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Overall Number of Participants Analyzed 11 10
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Summary Score: Mental Component Score 7.69  (16.10) 2.28  (10.42)
Summary Score: Physical Component Score 9.88  (12.31) 4.93  (9.83)
Subscale: Bodily Pain 26.64  (26.64) 8.00  (22.55)
Subscale: General Health 13.86  (18.78) 18.40  (23.55)
Subscale: Mental Health 20.00  (18.17) 2.50  (26.48)
Subscale: Physical Function 21.62  (35.45) 15.72  (17.54)
Subscale: Role Emotional 16.67  (45.95) 8.33  (24.85)
Subscale: Role Physical 34.09  (31.17) -1.25  (23.90)
Subscale: Social Functioning 21.59  (35.83) 7.50  (25.14)
Subscale: Vitality 10.61  (26.03) 8.13  (12.86)
7.Secondary Outcome
Title Change From Baseline in Health Assessment Questionnaire–Disability Index (HAQ-DI)
Hide Description The Stanford HAQ-DI is a patient-reported questionnaire specific for RA. It consists of 20 questions referring to eight component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. The questionnaire was provided in a certified translation of the local languages at the participating sites and was scored based on the instructions from the Stanford University Medical Center.The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction.
Time Frame Baseline, 24 Months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Intent−to−Treat (ITT) population for whom data was available at baseline and month 24.
Arm/Group Title Arm A: 500 mg Rituximab Arm B: 1000 mg Rituximab
Hide Arm/Group Description:
Rituximab: 1000 mg IV on Days 1 and 15 of the first cycle; 500 mg IV on Days 1 and 15 of each subsequent 6-month cycle (Months 6, 12, and 18). Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. Methotrexate: 15–25 mg/wk oral or parenteral (10–14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Rituximab: 1000 mg IV on Days 1 and 15 of each 12-month cycle (Rituximab cycles were administered at baseline and Month 12). For the Month 6 and 18 cycles, rituximab or placebo was administered. Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. For the Months 6 and 18 cycles, IV saline was administered prior to each rituximab or placebo infusion. Methotrexate: 15–25 mg/wk oral or parenteral (10–14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Overall Number of Participants Analyzed 11 10
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
-0.60  (0.87) -0.45  (0.72)
8.Secondary Outcome
Title Change From Baseline in Functional Assessment for Chronic Illness Therapy–Fatigue (FACIT-F)
Hide Description FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the patient’s response to the questions (with the exception of 2 negatively stated), the greater the patient’s fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the patient’s response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the patient’s health status.
Time Frame Baseline, 24 Months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Intent−to−Treat (ITT) population for whom data was available at baseline and month 24.
Arm/Group Title Arm A: 500 mg Rituximab Arm B: 1000 mg Rituximab
Hide Arm/Group Description:
Rituximab: 1000 mg IV on Days 1 and 15 of the first cycle; 500 mg IV on Days 1 and 15 of each subsequent 6-month cycle (Months 6, 12, and 18). Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. Methotrexate: 15–25 mg/wk oral or parenteral (10–14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Rituximab: 1000 mg IV on Days 1 and 15 of each 12-month cycle (Rituximab cycles were administered at baseline and Month 12). For the Month 6 and 18 cycles, rituximab or placebo was administered. Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. For the Months 6 and 18 cycles, IV saline was administered prior to each rituximab or placebo infusion. Methotrexate: 15–25 mg/wk oral or parenteral (10–14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Overall Number of Participants Analyzed 11 10
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
9.64  (15.54) 8.80  (12.15)
9.Secondary Outcome
Title DAS28-4 Erythrocyte Sedimentation Rate(ESR)
Hide Description The DAS28-4(ESR) score is a measure of the subject’s disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient’s global assessment of disease activity (mm), and ESR. DAS28-4(ESR) scores range from 0 - 10, where a score of less than or equal to 3.2 implies well controlled disease and greater than or equal to 5.1 implies active disease In this trial, CRP rather than ESR was used, unless the CRP value was missing at both Day 1 and screening, in which case ESR value was used.
Time Frame 24 Months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Intent−to−Treat (ITT) for whom data was available at baseline and month 24.
Arm/Group Title Arm A: 500 mg Rituximab Arm B: 1000 mg Rituximab
Hide Arm/Group Description:
Rituximab: 1000 mg IV on Days 1 and 15 of the first cycle; 500 mg IV on Days 1 and 15 of each subsequent 6-month cycle (Months 6, 12, and 18). Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. Methotrexate: 15–25 mg/wk oral or parenteral (10–14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Rituximab: 1000 mg IV on Days 1 and 15 of each 12-month cycle (Rituximab cycles were administered at baseline and Month 12). For the Month 6 and 18 cycles, rituximab or placebo was administered. Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. For the Months 6 and 18 cycles, IV saline was administered prior to each rituximab or placebo infusion. Methotrexate: 15–25 mg/wk oral or parenteral (10–14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Overall Number of Participants Analyzed 11 10
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
4.25  (1.98) 4.32  (1.39)
10.Secondary Outcome
Title Change From Baseline in Rheumatoid Factor (RF)
Hide Description Serum levels of rheumatoid factor at baseline, month 24 and change from baseline to month 24.
Time Frame Baseline, 24 Months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Safety-Evaluable population for whom data was available at baseline and month 24.
Arm/Group Title Arm A: 500 mg Rituximab Arm B: 1000 mg Rituximab
Hide Arm/Group Description:
Rituximab: 1000 mg IV on Days 1 and 15 of the first cycle; 500 mg IV on Days 1 and 15 of each subsequent 6-month cycle (Months 6, 12, and 18). Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. Methotrexate: 15–25 mg/wk oral or parenteral (10–14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Rituximab: 1000 mg IV on Days 1 and 15 of each 12-month cycle (Rituximab cycles were administered at baseline and Month 12). For the Month 6 and 18 cycles, rituximab or placebo was administered. Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. For the Months 6 and 18 cycles, IV saline was administered prior to each rituximab or placebo infusion. Methotrexate: 15–25 mg/wk oral or parenteral (10–14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Overall Number of Participants Analyzed 11 10
Mean (Standard Deviation)
Unit of Measure: IU/mL
Baseline 542.8  (1011.6) 243.7  (280.2)
Month 24 43.0  (70.8) 41.4  (34.3)
Change from Baseline to Month 24 -499.8  (946.9) -202.3  (279.1)
11.Secondary Outcome
Title Change From Baseline in Cyclic Citrullinated Peptide (CCP) Antibodies/Cytokines
Hide Description Because of the different laboratory methods that were used to measure anti-CCP antibody levels, no summary statistics were calculated.
Time Frame Baseline, 24 Months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm A: 500 mg Rituximab Arm B: 1000 mg Rituximab
Hide Arm/Group Description:
Rituximab: 1000 mg IV on Days 1 and 15 of the first cycle; 500 mg IV on Days 1 and 15 of each subsequent 6-month cycle (Months 6, 12, and 18). Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. Methotrexate: 15–25 mg/wk oral or parenteral (10–14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Rituximab: 1000 mg IV on Days 1 and 15 of each 12-month cycle (Rituximab cycles were administered at baseline and Month 12). For the Month 6 and 18 cycles, rituximab or placebo was administered. Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. For the Months 6 and 18 cycles, IV saline was administered prior to each rituximab or placebo infusion. Methotrexate: 15–25 mg/wk oral or parenteral (10–14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Duration includes safety-evaluable subjects during the 2-year treatment period; in addition Serious adverse events that occurred during safety follow-up.
Adverse Event Reporting Description A total of 42 subjects were randomized into the trial, 21 in Group A (500 mg rituximab retreatment regimen) and 21 in Group B (1000 mg rituximab retreatment regimen). Twenty subjects in Group B were treated with study drug and included in the safety-evaluable population.
 
Arm/Group Title Arm A: 500 mg Rituximab Arm B: 1000 mg Rituximab
Hide Arm/Group Description Rituximab: 1000 mg IV on Days 1 and 15 of the first cycle; 500 mg IV on Days 1 and 15 of each subsequent 6-month cycle (Months 6, 12, and 18). Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. Methotrexate: 15–25 mg/wk oral or parenteral (10–14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk). Rituximab: 1000 mg IV on Days 1 and 15 of each 12-month cycle (Rituximab cycles were administered at baseline and Month 12). For the Month 6 and 18 cycles, rituximab or placebo was administered. Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. For the Months 6 and 18 cycles, IV saline was administered prior to each rituximab or placebo infusion. Methotrexate: 15–25 mg/wk oral or parenteral (10–14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).
All-Cause Mortality
Arm A: 500 mg Rituximab Arm B: 1000 mg Rituximab
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Arm A: 500 mg Rituximab Arm B: 1000 mg Rituximab
Affected / at Risk (%) Affected / at Risk (%)
Total   3/21 (14.29%)   2/20 (10.00%) 
Cardiac disorders     
DEATH  1 [1]  0/21 (0.00%)  1/20 (5.00%) 
General disorders     
NON−CARDIAC CHEST PAIN  1  1/21 (4.76%)  0/20 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
MALIGNANT MELANOMA  1  0/21 (0.00%)  1/20 (5.00%) 
UTERINE LEIOMYOMA  1  1/21 (4.76%)  0/20 (0.00%) 
Nervous system disorders     
INTRACRANIAL ANEURYSM  1  1/21 (4.76%)  0/20 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
[1]
CARDIAC ARREST
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm A: 500 mg Rituximab Arm B: 1000 mg Rituximab
Affected / at Risk (%) Affected / at Risk (%)
Total   21/21 (100.00%)   14/20 (70.00%) 
Gastrointestinal disorders     
Nausea  1  5/21 (23.81%)  1/20 (5.00%) 
Vomiting  1  2/21 (9.52%)  2/20 (10.00%) 
Diarrhea  1  4/21 (19.05%)  1/20 (5.00%) 
Dry mouth  1  2/21 (9.52%)  0/20 (0.00%) 
General disorders     
Fatigue  1  2/21 (9.52%)  0/20 (0.00%) 
Infections and infestations     
Upper respiratory tract infection  1  3/21 (14.29%)  7/20 (35.00%) 
Sinusitis  1  6/21 (28.57%)  1/20 (5.00%) 
Urinary tract infection  1  2/21 (9.52%)  3/20 (15.00%) 
Fungal infection  1  1/21 (4.76%)  2/20 (10.00%) 
Bronchitis  1  3/21 (14.29%)  0/20 (0.00%) 
Investigations     
Liver function test abnormal  1  0/21 (0.00%)  2/20 (10.00%) 
Musculoskeletal and connective tissue disorders     
Pain in extremity  1  4/21 (19.05%)  2/20 (10.00%) 
Back pain  1  4/21 (19.05%)  1/20 (5.00%) 
Arthralgia  1  5/21 (23.81%)  2/20 (10.00%) 
Joint swelling  1  2/21 (9.52%)  1/20 (5.00%) 
Rheumatoid arthritis  1  3/21 (14.29%)  2/20 (10.00%) 
Nervous system disorders     
Headache  1  2/21 (9.52%)  0/20 (0.00%) 
Dizziness  1  2/21 (9.52%)  1/20 (5.00%) 
Paresthesia  1  2/21 (9.52%)  0/20 (0.00%) 
Insomnia  1  4/21 (19.05%)  3/20 (15.00%) 
Anxiety  1  1/21 (4.76%)  2/20 (10.00%) 
Depression  1  2/21 (9.52%)  1/20 (5.00%) 
Respiratory, thoracic and mediastinal disorders     
Nasal congestion  1  1/21 (4.76%)  2/20 (10.00%) 
Rhinitis, allergic  1  0/21 (0.00%)  2/20 (10.00%) 
Dyspnoea  1  2/21 (9.52%)  0/20 (0.00%) 
Cough  1  0/21 (0.00%)  3/20 (15.00%) 
Skin and subcutaneous tissue disorders     
Rash  1  4/21 (19.05%)  3/20 (15.00%) 
Pruritus  1  3/21 (14.29%)  1/20 (5.00%) 
Vascular disorders     
Hypertension  1  2/21 (9.52%)  2/20 (10.00%) 
Hot flush  1  2/21 (9.52%)  0/20 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Because of the limited sample size, interpretation of these results should be made with caution and therefore definitive conclusions cannot be made regarding differences between the two retreatment regimens studied.
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
Name/Title: Medical Communications
Organization: Hoffman-LaRoche
Phone: 800-821-8590
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00243412     History of Changes
Other Study ID Numbers: U3377g
First Submitted: October 21, 2005
First Posted: October 24, 2005
Results First Submitted: March 24, 2011
Results First Posted: October 7, 2011
Last Update Posted: October 7, 2011