Rheumatoid ArthritisPhase 2RUMBANCT00243412
A Study of the Safety and Efficacy of Rituximab in Patients With Moderate to Severe Rheumatoid Arthritis Receiving Methotrexate
A Phase 2 study testing folate, methotrexate and methylprednisolone in people with Rheumatoid Arthritis, run by Genentech, Inc..
Trial summary
This was a Phase II, randomized, double-blind, multicenter study designed to evaluate the safety and efficacy of rituximab, administered at two different regimens for 2 years, in patients with moderate to severe active rheumatoid arthritis (RA) receiving stable doses of methotrexate (MTX). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- folate, methotrexate and methylprednisolone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- No sites listed yet
- Study dates
- Aug 2005to Feb 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of RA for at least 6 months.
- Inadequate response to MTX
- Use of folate
- If female and of childbearing potential, have a negative serum pregnancy test within 8 weeks prior to first rituximab infusion
Who cannot join
- Diagnosis of juvenile idiopathic arthritis (also known as juvenile rheumatoid arthritis) and/or RA before age 16
- Any surgical procedure, including bone/joint surgery or planned surgery within 8 weeks prior to screening or within 16 weeks of Week 1 (Day 1) visit
- Inflammatory arthritis other than RA (e.g., inflammatory bowel disease, systemic lupus erythematosus (SLE), or psoriatic arthritis)
- Functional Class IV as defined by the American College of Rheumatology (ACR) classification of functional status in RA
- Use of disease-modifying anti-rheumatic drugs (DMARDs) other than MTX within 4 weeks prior to randomization (8 weeks prior for infliximab, adalimumab, or leflunomide)
- Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer)
Show all 23Show fewer
- Previous treatment with Tysabri<TM> (natalizumab)
- Previous treatment with rituximab
- Previous treatment with any cell-depleting therapies, including investigational agents
- Treatment with IV \&-globulin or Prosorba(R) Column within the previous 6 months
- Use of intra-articular or parenteral corticosteroids within 4 weeks prior to screening visit
- Receipt of a vaccine within 4 weeks prior to Day 1 infusion
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
- Primary or secondary immunodeficiency (history of or active)
- Evidence of significant uncontrolled concomitant diseases such as cardiovascular disease, nervous system, renal, hepatic, endocrine, gastrointestinal, or pulmonary disease, including any pulmonary or other condition that would preclude subject participation over the ensuing 2 years
- Known active bacterial, viral, fungal, mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds)
- History of recurrent significant infection or any significant episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening
- History of significant cytopenias or other bone marrow disorders
- History of cancer, including solid tumors and hematologic malignancies (except basal cell and squamous cell carcinoma of the skin that have been excised and cured)
- Pregnant or nursing (breast feeding) women
- Lack of peripheral venous access
- Chronic daily use of narcotic analgesics
- History of alcohol, drug, or chemical abuse within 6 months prior to screening
About this study
Official title: A Double-Blind, Randomized, Multicenter, Phase II Study of the Safety and Efficacy of Two Rituximab Regimens in Subjects With Moderate to Severe Active Rheumatoid Arthritis Receiving Stable Doses of Methotrexate
This was a Phase II, randomized, double-blind, multicenter study designed to evaluate the safety and efficacy of rituximab, administered at two different regimens for 2 years, in patients with moderate to severe active rheumatoid arthritis (RA) receiving stable doses of methotrexate (MTX).
- Conditions
- Rheumatoid Arthritis
- Being tested
- folate, methotrexate, methylprednisolone, Placebo, Rituximab
- Keywords
- Rituxan, RA
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
folateDrug
Minimum of 1 mg/day oral (or folinic acid 5 mg/week)
methotrexateDrug
15-25 mg/week oral or parenteral (10-14 mg/week if intolerant)
100 mg intravenous (IV) prior to each rituximab infusion (For Arm B, for the Months 6 and 18 cycles, IV saline was administered prior to each placebo infusion)
PlaceboDrug
To maintain the blind, patients in Arm B (Rituximab 1000 mg) received placebo infusions at Months 6 and 18.
RituximabDrug
500 mg or 1000 mg IV*2.
| Study group | Role | What they receive |
|---|---|---|
| Arm A: 500 mg Rituximab | Experimental | 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). Receives: Drug: folate; Drug: methotrexate; Drug: methylprednisolone; Drug: Rituximab |
| Arm B: 1000 mg Rituximab | Experimental | 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). Receives: Drug: folate; Drug: methotrexate; Drug: methylprednisolone; Drug: Placebo; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
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.
Measured: 24 months
Secondary outcomes (10)
Change From Baseline in Disease Activity Score 28-4 C-reactive Protein (DAS28-4(CRP))
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).
Measured: Baseline, 24 months
Number of Participants With American College of Rheumatology Responses (ACR20, ACR50, and ACR70)
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.
Measured: Baseline, 24 months
Number of Participants With American College of Rheumatology (ACR) Major Clinical Response and/or Remission
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.
Measured: 24 months
Number of Participants With European League Against Rheumatism (EULAR) Response and Remission Using Disease Activity Score 28-4 (DAS28-4)C-reactive Protein (CRP)
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.
Measured: Baseline, 24 months
Change From Baseline in Short Form 36 (SF 36) Summary and Subscale Scores
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.
Measured: Baseline, 24 Months
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI)
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.
Measured: Baseline, 24 Months
Change From Baseline in Functional Assessment for Chronic Illness Therapy-Fatigue (FACIT-F)
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.
Measured: Baseline, 24 Months
DAS28-4 Erythrocyte Sedimentation Rate(ESR)
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.
Measured: 24 Months
Change From Baseline in Rheumatoid Factor (RF)
Serum levels of rheumatoid factor at baseline, month 24 and change from baseline to month 24.
Measured: Baseline, 24 Months
Change From Baseline in Cyclic Citrullinated Peptide (CCP) Antibodies/Cytokines
Because of the different laboratory methods that were used to measure anti-CCP antibody levels, no summary statistics were calculated.
Measured: Baseline, 24 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2005 (estimated)
- Study startAug 2005
- Primary completionFeb 2009
- Study completionFeb 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Genentech, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genentech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- William Reiss, Pharm.D., Study director, Genentech, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00243412
- Sponsor's protocol ID
- U3377g
- Acronym
- RUMBA
- Status last verified
- Sep 2011
- First submitted
- 21 Oct 2005
- Last updated
- 7 Oct 2011
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Randomized, Multicenter, Phase II Study of the Safety and Efficacy of Two Rituximab Regimens in Subjects With Moderate to Severe Active Rheumatoid Arthritis Receiving Stable Doses of Methotrexate
- ClinicalTrials.gov ID
- NCT00243412
- Acronym / sponsor ID
- RUMBA / U3377g
- Conditions
- Rheumatoid Arthritis
- Keywords
- Rituxan, RA
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Genentech, Inc.Industry (pharma, biotech, devices)
- Study start
- Aug 2005
- Primary completion
- Feb 2009 (actual)
- Study completion
- Feb 2009 (actual)
- First posted
- 24 Oct 2005 (estimated)
- Results
- Posted 7 Oct 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a Phase II, randomized, double-blind, multicenter study designed to evaluate the safety and efficacy of rituximab, administered at two different regimens for 2 years, in patients with moderate to severe active rheumatoid arthritis (RA) receiving stable doses of methotrexate (MTX).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: 500 mg Rituximab | Experimental | Drug: folate, Drug: methotrexate, Drug: methylprednisolone, Drug: RituximabRituximab: 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). |
| Arm B: 1000 mg Rituximab | Experimental | Drug: folate, Drug: methotrexate, Drug: methylprednisolone, Drug: Placebo, Drug: RituximabRituximab: 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). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosis of RA for at least 6 months.
- Inadequate response to MTX
- Use of folate
- If female and of childbearing potential, have a negative serum pregnancy test within 8 weeks prior to first rituximab infusion
Key exclusion criteria (23 listed)
- Diagnosis of juvenile idiopathic arthritis (also known as juvenile rheumatoid arthritis) and/or RA before age 16
- Any surgical procedure, including bone/joint surgery or planned surgery within 8 weeks prior to screening or within 16 weeks of Week 1 (Day 1) visit
- Inflammatory arthritis other than RA (e.g., inflammatory bowel disease, systemic lupus erythematosus (SLE), or psoriatic arthritis)
- Functional Class IV as defined by the American College of Rheumatology (ACR) classification of functional status in RA
- Use of disease-modifying anti-rheumatic drugs (DMARDs) other than MTX within 4 weeks prior to randomization (8 weeks prior for infliximab, adalimumab, or leflunomide)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| folateMinimum of 1 mg/day oral (or folinic acid 5 mg/week) | Drug | Arm A: 500 mg Rituximab, Arm B: 1000 mg Rituximab |
| methotrexate15-25 mg/week oral or parenteral (10-14 mg/week if intolerant) | Drug | Arm A: 500 mg Rituximab, Arm B: 1000 mg Rituximab |
| methylprednisolone100 mg intravenous (IV) prior to each rituximab infusion (For Arm B, for the Months 6 and 18 cycles, IV saline was administered prior to each placebo infusion) | Drug | Arm A: 500 mg Rituximab, Arm B: 1000 mg Rituximab |
| PlaceboTo maintain the blind, patients in Arm B (Rituximab 1000 mg) received placebo infusions at Months 6 and 18. | Drug | Arm B: 1000 mg Rituximab |
| Rituximab500 mg or 1000 mg IV*2. | Drug | Arm A: 500 mg Rituximab, Arm B: 1000 mg Rituximab |
Primary outcome
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)
Time frame: 24 months
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.
10 secondary outcomes
Change From Baseline in Disease Activity Score 28-4 C-reactive Protein (DAS28-4(CRP))
Time frame: Baseline, 24 months
Number of Participants With American College of Rheumatology Responses (ACR20, ACR50, and ACR70)
Time frame: Baseline, 24 months
Number of Participants With American College of Rheumatology (ACR) Major Clinical Response and/or Remission
Time frame: 24 months
Number of Participants With European League Against Rheumatism (EULAR) Response and Remission Using Disease Activity Score 28-4 (DAS28-4)C-reactive Protein (CRP)
Time frame: Baseline, 24 months
Change From Baseline in Short Form 36 (SF 36) Summary and Subscale Scores
Time frame: Baseline, 24 Months
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI)
Time frame: Baseline, 24 Months
Change From Baseline in Functional Assessment for Chronic Illness Therapy-Fatigue (FACIT-F)
Time frame: Baseline, 24 Months
DAS28-4 Erythrocyte Sedimentation Rate(ESR)
Time frame: 24 Months
Change From Baseline in Rheumatoid Factor (RF)
Time frame: Baseline, 24 Months
Change From Baseline in Cyclic Citrullinated Peptide (CCP) Antibodies/Cytokines
Time frame: Baseline, 24 Months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2011.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William Reiss, Pharm.D. study director
Genentech, Inc.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing folate, methotrexate and methylprednisolone in people with Rheumatoid Arthritis, run by Genentech, Inc..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Oct 2011. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Oct 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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) (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2011.