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CompletedNCT00443651SUNDIALUpdated Apr 17, 2017Results posted

A Study of the Safety of Rituximab in Combination With Other Anti-Rheumatic Drugs in Subjects With Active Rheumatoid Arthritis

A Phase 3 interventional study of Rituximab and Anti-inflammatory drugs in Rheumatoid Arthritis, sponsored by Genentech, Inc.. Completed. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2017-04-17.

Sponsored by Genentech, Inc. (part of Hoffmann-La Roche) · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
578
Allocation
Non-randomized
Ages
18 Years to 80 Years
Sex
All
01

Study summary

This is a Phase III, open-label study of a total of approximately 560 subjects with active rheumatoid arthritis (RA) who have had an inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDs). Enrollment in the study was conducted in two stages. In Stage I of the study, approximately 400 subjects receiving non-biological DMARDs (with the exception of methotrexate [MTX] monotherapy or MTX and leflunomide combination therapy) were enrolled. In Stage II of the study, approximately 160 subjects receiving a Federal Drug Administration-approved biological DMARD at the time of screening were enrolled.

02

Conditions studied

  • Rheumatoid Arthritis

Keywords

  • Rituxan
  • RA
  • DMARD
  • Active Rheumatoid Arthritis
03

In context

Arthritis, Rheumatoid

2,962 studies on the registry are indexed under Arthritis, Rheumatoid; 396 are open to participants now.

This study's enrollment of 578 is above the median of 94 across 2,027 interventional studies indexed under Arthritis, Rheumatoid.

Browse Arthritis, Rheumatoid studies →

Lead sponsor

Genentech, Inc. is the lead sponsor of 517 studies on the registry; 22 are open to participants now.

Of its 95 completed or terminated interventional studies of FDA-regulated products, 52 (55%) have results posted.

First submitted after Genentech, Inc. became part of Hoffmann-La Roche.

Browse Genentech, Inc. studies →All Hoffmann-La Roche studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Inclusion Criteria (Stage I):

  • Male or female subjects, between 18 and 80 years of age, who have a documented diagnosis of active rheumatoid arthritis (RA) for ≥ 6 months
  • Receiving treatment for RA on an outpatient basis
  • Have had an inadequate response to at least one non-biological disease-modifying anti-rheumatic drug (DMARD) and have been receiving this DMARD(s) for ≥ 12 weeks prior to baseline, with stable dose greater than or equal to 4 weeks prior to baseline
  • Demonstrated tolerability to currently prescribed DMARDs
  • If taking a background corticosteroid, use of the corticosteroid must be at a stable dose during the 4 weeks prior to the first day of treatment with rituximab (Day 1)
  • Use of one nonsteroidal anti-inflammatory drug (NSAID) is permitted if the dose is stable for ≥ 2 weeks prior to Day 1

Exclusion Criteria (Stage I):

  • Rheumatic autoimmune disease other than RA or significant systemic involvement secondary to RA (including but not limited to vasculitis, pulmonary fibrosis, or Felty's syndrome)
  • Functional Class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in Rheumatoid Arthritis
  • History of or current inflammatory joint disease other than RA or other systemic autoimmune disorder
  • Diagnosis of juvenile idiopathic arthritis, or juvenile RA, and/or RA before age 16 years
  • Any surgical procedure, including bone/joint surgery/synovectomy (including joint fusion or replacement) within 12 weeks prior to baseline or planned within 24 weeks of enrollment
  • Lack of peripheral venous access
  • Significant cardiac or pulmonary disease (including obstructive pulmonary disease)
  • Evidence of significant uncontrolled concomitant disease such as, but not limited to, nervous system, renal, hepatic, endocrine, or gastrointestinal disorders that, in the investigator's opinion, would preclude subject participation
  • Primary or secondary immunodeficiency (history of or currently active), including known history of human immunodeficiency virus (HIV) infection
  • Known active infection of any kind (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with intravenous (IV) antibiotics within 4 weeks of baseline or completion of oral antibiotics within 2 weeks prior to baseline
  • History of medically significant opportunistic infection
  • History of serious recurrent or chronic infection
  • History of deep space/tissue infection within 52 weeks prior to baseline
  • History of cancer, including solid tumors, hematologic malignancies, and carcinoma in situ (except basal cell and squamous cell carcinoma of the skin that have been excised and cured)
  • History of significant cytopenias or other bone marrow disorders
  • History of alcohol, drug, or chemical abuse within 24 weeks prior to baseline
  • Pregnancy or lactation
  • Neuropathies and neurovasculopathies that might interfere with pain evaluation
  • Methotrexate (MTX) monotherapy at the time of screening
  • Concurrent treatment with MTX and leflunomide in combination
  • Concurrent treatment with any biologic agent
  • Prior to Day 1, subjects will be discontinued from all DMARDs/combinations that are prohibited in the protocol
  • History of a severe allergic or anaphylactic reaction to a biologic agent, or known hypersensitivity to any component of rituximab or to murine proteins
  • Previous treatment with an anti-α4 integrin agent
  • Previous treatment with any cell-depleting therapies, including investigational agents
  • Receipt of any vaccine within 28 days prior to baseline
  • Intolerance or contraindications to IV corticosteroids
  • Receipt of IV immunoglobulin (IVIG) or Prosorba\<TM> column within 6 months prior to baseline
  • Any previous treatment with rituximab
  • Positive hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody

Inclusion Criteria (Stage II):

  • Male or female subjects, between 18 and 80 years of age, who have a documented diagnosis of active RA for ≥ 6 months, diagnosed according to the revised 1987 ACR criteria for the classification of RA
  • Receiving treatment for RA on an outpatient basis
  • Have had an inadequate response to at least one biologic DMARD and have been receiving this agent at screening and for ≥ 12 weeks prior to baseline, with stable dose greater than or equal to 4 weeks prior to baseline
  • Have demonstrated tolerability to currently prescribed DMARDs/biologics
  • If taking a background corticosteroid, use of the corticosteroid must be at a stable dose during the 4 weeks prior to baseline
  • Use of one NSAID is permitted if the dose is stable for ≥ 2 weeks prior to baseline

Exclusion Criteria (Stage II):

  • Rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA (including but not limited to vasculitis, pulmonary fibrosis, or Felty's syndrome)
  • Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis
  • History of, or current, inflammatory joint disease other than RA or other systemic autoimmune disorder
  • Diagnosis of juvenile idiopathic arthritis, or juvenile RA, and/or RA before age 16 years
  • Any surgical procedure, including bone/joint surgery/synovectomy (including joint fusion or replacement) within 12 weeks prior to baseline or planned within 24 weeks of randomization
  • Lack of peripheral venous access
  • Significant cardiac or pulmonary disease (including obstructive pulmonary disease)
  • Evidence of significant uncontrolled concomitant disease such as, but not limited to, nervous system, renal, hepatic, endocrine or gastrointestinal disorders that, in the investigator's opinion, would preclude subject participation
  • Primary or secondary immunodeficiency (history of or currently active), including known history of HIV infection
  • Known active infection of any kind (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of baseline or completion of oral antibiotics within 2 weeks prior to baseline
  • History of medically significant opportunistic infection
  • History of serious recurrent or chronic infection
  • History of deep space/tissue infection within 52 weeks prior to baseline
  • History of cancer, including solid tumors, hematologic malignancies, and carcinoma in situ (except basal cell and squamous cell carcinoma of the skin that have been excised and cured)
  • History of significant cytopenias or other bone marrow disorders
  • History of alcohol, drug, or chemical abuse within 24 weeks prior to baseline
  • Pregnancy or lactation
  • Neuropathies and neurovasculopathies that might interfere with pain evaluation
  • Infliximab monotherapy at the time of screening (infliximab should be in combination with MTX)
  • Concurrent treatment with MTX and leflunomide in combination
  • Concurrent treatment with more than one biologic agent
  • Prior to Day 1, subjects will be discontinued from all DMARDs/combinations that are prohibited in the protocol
  • History of a severe allergic or anaphylactic reaction to a biologic agent, or known hypersensitivity to any component of rituximab or to murine proteins
  • Previous treatment with an anti-α4 integrin agent
  • Previous treatment with any cell-depleting therapies
  • Treatment with any investigational agent within 28 days of baseline or 5 half-lives of the investigational drug (whichever is the longer)
  • Receipt of any vaccine within 28 days prior to baseline
  • Intolerance or contraindications to IV corticosteroids
  • Receipt of IVIG or Prosorba\<TM> column within 6 months prior to baseline
  • Any previous treatment with rituximab
  • Positive hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody
  • Positive purified protein derivative (PPD) skin test not adequately treated according to Center for Disease Control (CDC) guidelines
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
578 participants (actual)

Study arms

  • Experimental
    Rituximab 1000 mg (Stage I patients)

    Stage I patients received 2 doses of rituximab 1000 mg administered intravenously (IV) 14 days apart at the beginning of the study (Days 1 and 15). During Weeks 24 to 40, patients who met disease activity and safety criteria were eligible to receive 2 additional IV infusions of rituximab 1000 mg given 14 days apart. Concomitant non-biological disease-modifying anti-rheumatic drug (DMARD) therapy, at a stable dose and route, was continued during the study, except for protocol defined prohibited DMARDs/combinations.

    Drug: Rituximab · Drug: Anti-inflammatory drugs

  • Experimental
    Rituximab 500 mg (Stage II patients)

    Stage II patients received 2 doses of rituximab 500 mg administered intravenously (IV) 14 days apart at the beginning of the study (Days 1 and 15). During Weeks 24 to 40, patients who met disease activity and safety criteria were eligible to receive 2 additional IV infusions of rituximab 500 mg given 14 days apart. Concomitant biological and non-biological disease-modifying anti-rheumatic drug (DMARD) therapy, at a stable dose and route, was continued during the study, except for protocol defined prohibited DMARDs/combinations.

    Drug: Rituximab · Drug: Anti-inflammatory drugs

Interventions

  • DrugRituximab

    Rituximab was supplied as a concentrate for IV administration at a concentration of 10 mg/mL in 500 mg (50 mL) single-use vials.

  • DrugAnti-inflammatory drugs

    Each rituximab infusion was preceded by methylprednisolone 100 mg IV. Use of stable doses of oral corticosteroids was permitted (≤ 10 mg of prednisone or equivalent per day) as were stable doses of nonsteroidal anti-inflammatory drugs (NSAIDs).

06

What researchers measure

Primary outcomes

  1. Percentage of Patients Developing a Serious Adverse Event (SAE) Within 24 Weeks After Receiving the First Course of Rituximab Treatment

    An adverse event (AE) is any unfavorable and unintended sign, symptom, significantly abnormal laboratory finding, or disease temporally associated with the use of an investigational medical product or other protocol-imposed intervention. An AE was classified as an SAE if it: Resulted in death, persistent or significant disability/incapacity, or congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product; required or prolonged inpatient hospitalization; was life-threatening or considered a significant medical event by the investigator.

    Time frame: From first treatment with rituximab (Day 1) through Week 24

Secondary outcomes

  1. Percentage of Patients Who Developed a Serious Adverse Event (SAE) During or Within 24 Hours of Rituximab Infusions

    The percentage of patients developing a SAE during or within 24 hours of a rituximab infusion is reported separately for each of the 2 infusions in the first course of treatment (Days 1 and 15) and the second course of treatment (optional retreatment during Weeks 24 to 40). See the Primary Outcome Measure for a definition of a SAE.

    Time frame: From start of rituximab treatment through 24 hours

  2. Percentage of Patients Who Developed a Serious Adverse Event (SAE) Within 24 Weeks After Receiving the Second Course (Optional Retreatment) of Rituximab Treatment

    An adverse event (AE) is any unfavorable and unintended sign, symptom, significantly abnormal laboratory finding, or disease temporally associated with the use of an investigational medical product or other protocol-imposed intervention. An AE was classified as an SAE if it: Resulted in death, persistent or significant disability/incapacity, or congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product; required or prolonged inpatient hospitalization; was life-threatening or considered a significant medical event by the investigator.

    Time frame: From start of the second course of rituximab treatment through Week 48

  3. Percentage of Patients With an Improvement of 20%, 50%, and 70% in American College of Rheumatology (ACR) Scores (ACR20/50/70) From Baseline at Weeks 24 and 48

    Improvement must be seen in tender and swollen joint counts and in at least 3 of the following 5 parameters. Patient and physician assessment of patient disease activity (DA) in previous 24 hours on a visual analog scale (VAS, no DA to maximum DA); patient assessment of pain in previous 24 hours on a VAS (none to unbearable); 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 or, if missing, erythrocyte sedimentation rate.

    Time frame: Baseline to Week 24 and Week 48

  4. Percentage of Patients Achieving Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS 28-ESR) Remission and DAS 28-ESR Low Disease Activity Scores at Weeks 24 and 48

    DAS 28-ESR was calculated using counts of tender and swollen joints (28 joints, 28TJC and 28SJC), a patient assessment (PA) of disease activity (DA) in previous 24 hours on a visual analog scale (no DA to maximum DA), and ESR at the current visit, using the following formula: 0.56 × 28TJC + 0.28 × 28SJC + 0.70 × ln(ESR) + 0.014 × PADA. The DAS 28-ESR score ranges from 0 to 10, with higher scores indicating more rheumatoid arthritis. DAS28-ESR Remission was defined as a DAS 28-ESR score of \< 2.6. DAS28-ESR Low Disease Activity was defined as a DAS28-ESR score of ≤ 3.2.

    Time frame: Week 24 and Week 48

  5. Percentage of Patients With European League Against Rheumatism (EULAR) Good and Moderate Responses at Weeks 24 and 48

    Improvement in the post-baseline DAS 28-ESR score from baseline was used to determine the EULAR responses of moderate response and good response. The DAS 28-ESR score ranges from 0 to 10, with higher scores indicating more rheumatoid arthritis. For a post-baseline score ≤ 3.2, an improvement \> 0.6 to ≤ 1.2 was a moderate response and ≥ 1.2 a good response. For a post-baseline score \> 3.2 to ≤ 5.1, an improvement \> 0.6 was a moderate response. For a post-baseline score \> 5.1, an improvement ≥ 1.2 was a moderate response. A good response could not be achieved for post-baseline scores \> 3.2.

    Time frame: Baseline to Week 24 and Week 48

  6. Health Assessment Questionnaire-Disability Index (HAQ-DI) Change From Baseline at Weeks 24 and 48

    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 24 and Week 48

07

Results

Posted Aug 31, 2012

Participant flow

The study was conducted in 2 stages. Stage I: Patients with an inadequate response to non-biological disease-modifying antirheumatic drugs (DMARDS) were treated with rituximab 1000 mg. Stage II: Patients with an inadequate response to a biological DMARD were treated with rituximab 500 mg. Both groups continued to receive DMARDs.

Participant flow — Overall Study
MilestoneRituximab 1000 mg (Stage I Patients)Rituximab 500 mg (Stage II Patients)
Started401176
Week 24376160
Week 48338134
Completed306118
Not completed9558
Withdrew: Death15
Withdrew: Adverse event56
Withdrew: Lost to follow-up1812
Withdrew: Patient's/guardian's decision5830
Withdrew: Physician decision134
Withdrew: Pregnancy01

Outcome measures

PrimaryPercentage of Patients Developing a Serious Adverse Event (SAE) Within 24 Weeks After Receiving the First Course of Rituximab Treatment

An adverse event (AE) is any unfavorable and unintended sign, symptom, significantly abnormal laboratory finding, or disease temporally associated with the use of an investigational medical product or other protocol-imposed intervention. An AE was classified as an SAE if it: Resulted in death, persistent or significant disability/incapacity, or congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product; required or prolonged inpatient hospitalization; was life-threatening or considered a significant medical event by the investigator.

Time frame:
From first treatment with rituximab (Day 1) through Week 24
Reported as:
Number · Percentage of participants
Percentage of Patients Developing a Serious Adverse Event (SAE) Within 24 Weeks After Receiving the First Course of Rituximab Treatment
Percentage of participantsRituximab 1000 mg (Stage I Patients)Rituximab 500 mg (Stage II Patients)
Percentage of Patients Developing a Serious Adverse Event (SAE) Within 24 Weeks After Receiving the First Course of Rituximab Treatment6.09.1
SecondaryPercentage of Patients Who Developed a Serious Adverse Event (SAE) During or Within 24 Hours of Rituximab Infusions

The percentage of patients developing a SAE during or within 24 hours of a rituximab infusion is reported separately for each of the 2 infusions in the first course of treatment (Days 1 and 15) and the second course of treatment (optional retreatment during Weeks 24 to 40). See the Primary Outcome Measure for a definition of a SAE.

Time frame:
From start of rituximab treatment through 24 hours
Reported as:
Number · Percentage of participants
Percentage of Patients Who Developed a Serious Adverse Event (SAE) During or Within 24 Hours of Rituximab Infusions
Percentage of participantsRituximab 1000 mg (Stage I Patients)Rituximab 500 mg (Stage II Patients)
1st infusion, 1st course of treatment0.20.0
2nd infusion, 1st course of treatment0.00.0
1st infusion, 2nd course of treatment0.00.0
2nd infusion, 2nd course of treatment0.00.0
SecondaryPercentage of Patients Who Developed a Serious Adverse Event (SAE) Within 24 Weeks After Receiving the Second Course (Optional Retreatment) of Rituximab Treatment

An adverse event (AE) is any unfavorable and unintended sign, symptom, significantly abnormal laboratory finding, or disease temporally associated with the use of an investigational medical product or other protocol-imposed intervention. An AE was classified as an SAE if it: Resulted in death, persistent or significant disability/incapacity, or congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product; required or prolonged inpatient hospitalization; was life-threatening or considered a significant medical event by the investigator.

Time frame:
From start of the second course of rituximab treatment through Week 48
Reported as:
Number · Percentage of participants
Percentage of Patients Who Developed a Serious Adverse Event (SAE) Within 24 Weeks After Receiving the Second Course (Optional Retreatment) of Rituximab Treatment
Percentage of participantsRituximab 1000 mg (Stage I Patients)Rituximab 500 mg (Stage II Patients)
Percentage of Patients Who Developed a Serious Adverse Event (SAE) Within 24 Weeks After Receiving the Second Course (Optional Retreatment) of Rituximab Treatment7.26.1
SecondaryPercentage of Patients With an Improvement of 20%, 50%, and 70% in American College of Rheumatology (ACR) Scores (ACR20/50/70) From Baseline at Weeks 24 and 48

Improvement must be seen in tender and swollen joint counts and in at least 3 of the following 5 parameters. Patient and physician assessment of patient disease activity (DA) in previous 24 hours on a visual analog scale (VAS, no DA to maximum DA); patient assessment of pain in previous 24 hours on a VAS (none to unbearable); 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 or, if missing, erythrocyte sedimentation rate.

Time frame:
Baseline to Week 24 and Week 48
Reported as:
Number · Percentage of participants
Percentage of Patients With an Improvement of 20%, 50%, and 70% in American College of Rheumatology (ACR) Scores (ACR20/50/70) From Baseline at Weeks 24 and 48
Percentage of participantsRituximab 1000 mg (Stage I Patients)Rituximab 500 mg (Stage II Patients)
ACR20 at Week 2436.930.7
ACR50 at Week 2415.710.2
ACR70 at Week 247.75.1
ACR20 at Week 4850.648.9
ACR50 at Week 4825.922.7
ACR70 at Week 4811.09.1
SecondaryPercentage of Patients Achieving Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS 28-ESR) Remission and DAS 28-ESR Low Disease Activity Scores at Weeks 24 and 48

DAS 28-ESR was calculated using counts of tender and swollen joints (28 joints, 28TJC and 28SJC), a patient assessment (PA) of disease activity (DA) in previous 24 hours on a visual analog scale (no DA to maximum DA), and ESR at the current visit, using the following formula: 0.56 × 28TJC + 0.28 × 28SJC + 0.70 × ln(ESR) + 0.014 × PADA. The DAS 28-ESR score ranges from 0 to 10, with higher scores indicating more rheumatoid arthritis. DAS28-ESR Remission was defined as a DAS 28-ESR score of \< 2.6. DAS28-ESR Low Disease Activity was defined as a DAS28-ESR score of ≤ 3.2.

Time frame:
Week 24 and Week 48
Reported as:
Number · Percentage of participants
Percentage of Patients Achieving Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS 28-ESR) Remission and DAS 28-ESR Low Disease Activity Scores at Weeks 24 and 48
Percentage of participantsRituximab 1000 mg (Stage I Patients)Rituximab 500 mg (Stage II Patients)
DAS 28-ESR Remission at Week 24 (n=391, 171)8.46.4
DAS 28-ESR Low DA at Week 24 (n=391, 171)15.611.7
DAS 28-ESR Remission at Week 48 (n=389, 172)12.67.0
DAS 28-ESR Low DA at Week 48 (n=389, 172)23.422.1
SecondaryPercentage of Patients With European League Against Rheumatism (EULAR) Good and Moderate Responses at Weeks 24 and 48

Improvement in the post-baseline DAS 28-ESR score from baseline was used to determine the EULAR responses of moderate response and good response. The DAS 28-ESR score ranges from 0 to 10, with higher scores indicating more rheumatoid arthritis. For a post-baseline score ≤ 3.2, an improvement \> 0.6 to ≤ 1.2 was a moderate response and ≥ 1.2 a good response. For a post-baseline score \> 3.2 to ≤ 5.1, an improvement \> 0.6 was a moderate response. For a post-baseline score \> 5.1, an improvement ≥ 1.2 was a moderate response. A good response could not be achieved for post-baseline scores \> 3.2.

Time frame:
Baseline to Week 24 and Week 48
Reported as:
Number · Percentage of participants
Percentage of Patients With European League Against Rheumatism (EULAR) Good and Moderate Responses at Weeks 24 and 48
Percentage of participantsRituximab 1000 mg (Stage I Patients)Rituximab 500 mg (Stage II Patients)
Good EULAR Response at Week 2413.79.1
Moderate EULAR Response at Week 2439.234.1
Good EULAR Response at Week 4821.218.2
Moderate EULAR Response at Week 4844.143.8
SecondaryHealth Assessment Questionnaire-Disability Index (HAQ-DI) Change From Baseline at Weeks 24 and 48

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 24 and Week 48
Reported as:
Mean · Units on a scale
Health Assessment Questionnaire-Disability Index (HAQ-DI) Change From Baseline at Weeks 24 and 48
Units on a scaleRituximab 1000 mg (Stage I Patients)Rituximab 500 mg (Stage II Patients)
Week 24-0.28 ± 0.474-0.28 ± 0.495
Week 48-0.33 ± 0.508-0.32 ± 0.512

Adverse events

Collected over Adverse events (AE) were recorded from the time when informed consent was obtained until Week 48, Week 4 of the safety follow-up (SFU) period, or early discontinuation. Beyond Week 4 of the SFU period, only serious or infectious AEs were recorded.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Rituximab 1000 mg (Stage I Patients)—48/401 (12%)278/401 (69.3%)
Rituximab 500 mg (Stage II Patients)—27/176 (15.3%)128/176 (72.7%)
Most frequent serious events
Showing 10 of 69
Most frequent serious events
EventRituximab 1000 mg (Stage I Patients)Rituximab 500 mg (Stage II Patients)
Rheumatoid arthritisMusculoskeletal and connective tissue disorders2/4013/176
Ulna fractureInjury, poisoning and procedural complications0/4012/176
Chest painGeneral disorders4/4011/176
PneumoniaInfections and infestations4/4011/176
CellulitisInfections and infestations4/4011/176
BronchitisInfections and infestations1/4011/176
Septic shockInfections and infestations0/4011/176
Lumbar spinal stenosisMusculoskeletal and connective tissue disorders2/4011/176
ArthritisMusculoskeletal and connective tissue disorders0/4011/176
PericarditisCardiac disorders1/4011/176
Most frequent other events
Showing 10 of 21
Most frequent other events
EventRituximab 1000 mg (Stage I Patients)Rituximab 500 mg (Stage II Patients)
Rheumatoid arthritisMusculoskeletal and connective tissue disorders50/40128/176
Upper respiratory tract infectionInfections and infestations51/40127/176
HeadacheNervous system disorders38/40125/176
SinusitisInfections and infestations45/40123/176
NauseaGastrointestinal disorders31/40122/176
ArthralgiaMusculoskeletal and connective tissue disorders47/40112/176
Urinary tract infectionInfections and infestations45/40115/176
CoughRespiratory, thoracic and mediastinal disorders36/40110/176
BronchitisInfections and infestations35/40112/176
HypertensionVascular disorders28/40114/176

Baseline characteristics

Age, Customized
Age, Customized(Participants)Rituximab 1000 mg (Stage I Patients)Rituximab 500 mg (Stage II Patients)Total
18 - 25 years8513
26 - 35 years22830
36 - 45 years592685
46 - 55 years13248180
56 - 65 years13367200
66 - 75 years381957
76 - 85 years9312
> 85000
Sex: Female, Male
Sex: Female, Male(Participants)Rituximab 1000 mg (Stage I Patients)Rituximab 500 mg (Stage II Patients)Total
Female302154456
Male9922121
08

Study locations

No study locations are listed for this record.

09

References and documents

Publications

  • Rigby WF, Mease PJ, Olech E, Ashby M, Tole S. Safety of rituximab in combination with other biologic disease-modifying antirheumatic drugs in rheumatoid arthritis: an open-label study. J Rheumatol. 2013 May;40(5):599-604. doi: 10.3899/jrheum.120924. Epub 2013 Apr 1. PubMed 23547218 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 17, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00443651
Lead sponsor
Genentech, Inc.
Collaborators
Biogen
Responsible party
Sponsor
First posted
Mar 6, 2007
Start date
Jan 2007
Primary completion
May 2011
Completion
Feb 2013
Results posted
Aug 31, 2012
Last update
Apr 17, 2017

Study contacts

Micki Klearman, M.D.
study director · Genentech, Inc.
View the source record on ClinicalTrials.gov ↗

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