TriangleNCT00299104 · CITED IN SOURCE DOCUMENTS
A Study to Evaluate Rituximab in Combination With Methotrexate in Methotrexate-Naive Patients With Active Rheumatoid Arthritis
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2017-07-28
This is a phase III, randomized, controlled, double-blind, parallel group, international study in approximately 750 patients with active Rheumatoid Arthritis (RA) who are naive to Methotrexate (MTX) therapy. Rheumatoid Factor (RF)-positive and RF-negative patients will be enrolled and will be allocated equally between 3 treatment arms.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Change From Baseline in Modified Total Sharp Score (mTSS) From Screening at Week 52
Change From Baseline in Modified Sharp Erosion Score at Week 52
Percentage of Patients Without Radiographic Progression at Week 52
Percentage of Patients Without Radiographic Progression in Total Erosion Score at Week 52
Change From Baseline in Modified Joint Space Narrowing (JSN) Score at Week 52
Change From Baseline in the Modified Total Sharp Score at Week 24
Change From Baseline in the Total Erosion Score at Week 24
Change From Baseline in Modified Joint Space Narrowing (JSN) Score at Week 24
Percentage of Participants Without Radiographic Progression at Week 24
Percentage of Participants With American College of Rheumatology (ACR) ACR50 Response at Week 52
Change From Baseline in the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 52
Percentage of Participants With American College of Rheumatology (ACR) ACR70 Response at Week 52
Percentage of Participants With DAS28-ESR Remission at Week 52
Percentage of Participants With European League Against Rheumatism (EULAR) Good Response at Week 52
The Percentage of Participants With Major Clinical Response at Week 52
Percentage of Participants With DAS28-ESR Low Disease Activity at Week 52
Percentage of Participants With American College of Rheumatology (ACR) ACR20 Response at Week 52
Percentage of Participants With American College of Rheumatology (ACR) ACR90 Response at Week 52
Change in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Score From Baseline at Week 52
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 52
Change From Baseline in the SF-36 Physical Health Component Summary Score at Week 52 and Week 104
Change From Baseline in the SF-36 Mental Health Component Summary Score at Week 52 and Week 104
Percentage of Participants With Categorical Change in Health Assessment Questionnaire- Disability Index (HAQ-DI) From Baseline at Week 52
Percentage of Patients With Minimally Clinically Important Difference (MCID) in the SF-36 Physical Health Component Score at Week 52
Percentage of Patients With Minimally Clinically Important Difference (MCID) in the SF-36 Mental Health Component Score at Week 52
Change From Baseline in the Modified Total Sharp Score at Week 104
Change From Baseline in the Total Erosion Score at Week 104
Percentage of Participants Without Radiographic Progression at Week 104
Percentage of Participants Without Radiographic Progression in the Total Erosion Score at Week 104
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 104
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Inclusion criteria: * Adult patients 18-80 years of age * RA for ≥ 2 months; * Receiving outpatient treatment * Patients naive to, and considered to be candidates for, methotrexate treatment Exclusion criteria: * Rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA * Inflammatory joint disease other than RA, or other systemic autoimmune disorder * Diagnosis of juvenile rheumatoid arthritis, or RA before the age of 16 * Surgery within 12 weeks of study * Previous treatment with any approved or investigational biologic agent for RA, an anti-alpha4-integrin antibody or co-stimulation modulator, or cell-depleting therapy * Concurrent treatment with any biologic agent or DMARD other than methotrexate
- healthy Volunteers
- false
- maximum Age
- 80 Years
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
- intervention Names
- Drug: folate
- Drug: methotrexate
- Drug: methylprednisolone
- Drug: rituximab
- label
- Rituximab (0.5 g x 2) + Methotrexate
- type
- EXPERIMENTAL
- description
- Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
- intervention Names
- Drug: folate
- Drug: methotrexate
- Drug: methylprednisolone
- Drug: rituximab
- label
- Rituximab (1.0 g x 2) + Methotrexate
- type
- EXPERIMENTAL
- description
- Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.
- intervention Names
- Drug: folate
- Drug: methotrexate
- Drug: methylprednisolone
- Drug: placebo
- label
- Placebo + Methotrexate
- type
- PLACEBO_COMPARATOR
- interventions
- arm Group Labels
- Placebo + Methotrexate
- Rituximab (0.5 g x 2) + Methotrexate
- Rituximab (1.0 g x 2) + Methotrexate
- description
- Intravenous repeating dose
- name
- folate
- type
- DRUG
- arm Group Labels
- Placebo + Methotrexate
- Rituximab (0.5 g x 2) + Methotrexate
- Rituximab (1.0 g x 2) + Methotrexate
- description
- Oral or parenteral repeating dose
- name
- methotrexate
- type
- DRUG
- arm Group Labels
- Placebo + Methotrexate
- Rituximab (0.5 g x 2) + Methotrexate
- Rituximab (1.0 g x 2) + Methotrexate
- description
- Intravenous repeating dose
- name
- methylprednisolone
- type
- DRUG
- arm Group Labels
- Placebo + Methotrexate
- description
- Intravenous repeating dose
- name
- placebo
- type
- DRUG
- arm Group Labels
- Rituximab (0.5 g x 2) + Methotrexate
- Rituximab (1.0 g x 2) + Methotrexate
- description
- Intravenous repeating dose
- name
- rituximab
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- DOUBLE
- who Masked
- PARTICIPANT
- INVESTIGATOR
- primary Purpose
- TREATMENT
Enrollment
- count
- 755
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- Rate of progression in structural joint damage (PJD) by change in Total Modified Sharp Score (TMSS) from screening to Week 52 in the modified intent-to-treat (MITT) population. TMSS is the sum of the erosion score (ES) and the joint space narrowing (JSN) score and has a range of 0 to 398. The ES is the sum of joint scores collected for 46 joints and has a range of 0 to 230. The JSN is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change and higher scores represent a worsening of joint erosions and joint space narrowing.
- measure
- Change From Baseline in Modified Total Sharp Score (mTSS) From Screening at Week 52
- time Frame
- Baseline and week 52
- secondary Outcomes
- description
- Rate of progression in structural joint damage (PJD) by change in modified Sharp erosion score from screening to Week 52. The ES is the sum of joint scores collected for 46 joints and has a range of 0 to 230. A score of 0 would indicate no change and higher scores represent a worsening of joint erosions.
- measure
- Change From Baseline in Modified Sharp Erosion Score at Week 52
- time Frame
- Baseline and week 52
- description
- Percentage of patients without radiographic progression at Week 52, defined as change in total modified Sharp score (TMSS) \<= 0. TMSS is the sum of the erosion score (ES) and the joint space narrowing (JSN) score and has a range of 0 to 398. The ES is the sum of joint scores collected for 46 joints and has a range of 0 to 230. The JSN is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change.
- measure
- Percentage of Patients Without Radiographic Progression at Week 52
- time Frame
- Baseline, Week 52
- description
- No radiographic progression is defined as a change in the total erosion score at Week 52 of less than or equal to zero.
- measure
- Percentage of Patients Without Radiographic Progression in Total Erosion Score at Week 52
- time Frame
- Baseline, Week 52
- description
- Rate of progression in structural joint damage (PJD) by change in modified joint space narrowing (JSN) from screening to Week 52. The JSN is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change and higher scores represent a worsening of joint space narrowing.
- measure
- Change From Baseline in Modified Joint Space Narrowing (JSN) Score at Week 52
- time Frame
- Baseline and week 52
- description
- The modified total sharp score is the sum of the erosion score (ES) and the joint space narrowing (JSN) score and has a range of 0 to 398. The ES is the sum of joint scores collected for 46 joints and has a range of 0 to 230. The JSN is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change and higher scores represent a worsening of joint erosions and joint space narrowing.
- measure
- Change From Baseline in the Modified Total Sharp Score at Week 24
- time Frame
- Baseline, Week 24
- description
- Total Erosion Score is determined by evaluation of fourteen sites in each wrist and hand and six joints in each foot using an eight-point scale from 0 (normal: no erosions) to 3.5 (Very severe; erosions of 100% of the articular surfaces. The Total Erosion Score at Week 24 - Total Erosion Score at baseline is calculated.
- measure
- Change From Baseline in the Total Erosion Score at Week 24
- time Frame
- Baseline, Week 24
- description
- Joint Space Narrowing is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change and higher scores represent a worsening of joint space narrowing.
- measure
- Change From Baseline in Modified Joint Space Narrowing (JSN) Score at Week 24
- time Frame
- Baseline, Week 24
- description
- Percentage of patients without radiographic progression at Week 24 defined as change in total modified Sharp score (TMSS) ≤ 0. TMSS is the sum of the erosion score (ES) and the joint space narrowing (JSN) score and has a range of 0 to 398. The ES is the sum of joint scores collected for 46 joints and has a range of 0 to 230. The JSN is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change.
- measure
- Percentage of Participants Without Radiographic Progression at Week 24
- time Frame
- Baseline, Week 24
- description
- To achieve an ACR50 response requires at least a 50% improvement compared with baseline in both Total Joint Count and Swollen Joint Count, as well as a 50% improvement in three of five additional measurements from: * the physician's global assessment of disease activity * patient's global assessment of disease activity * patient's assessment of pain * HAQ-DI (Health Assessment Questionnaire disability index) * an acute phase reactant C-Reactive Protein (CRP). (If CRP was missing then Erythrocyte Sedimentation Rate (ESR) was used if available.)
- measure
- Percentage of Participants With American College of Rheumatology (ACR) ACR50 Response at Week 52
- time Frame
- Week 52
- description
- DAS28-ESR is calculated from the following formula: (0.56 \* TJC) + (0.28 \* SJC) + (0.70 \* ln ESR) + (0.014 \* GH) TJC = tender joint count, based on 28 joints SJC = swollen joint count, based on 28 joints ESR = erythrocyte sedimentation rate in mm/h GH = patient's global assessment of disease activity A DAS28-ESR score of 5.1 or above is considered to indicate high disease activity. Patients can also be defined as having low disease activity (DAS28-ESR ≤ 3.2) or remission (DAS28-ESR \< 2.6).
- measure
- Change From Baseline in the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 52
- time Frame
- Baseline, Week 52
- description
- To achieve an ACR70 response requires at least a 70% improvement compared with baseline in both Total Joint Count and Swollen Joint Count, as well as a 70% improvement in three of five additional measurements from: * the physician's global assessment of disease activity * patient's global assessment of disease activity * patient's assessment of pain * HAQ-DI (Health Assessment Questionnaire disability index) * an acute phase reactant C-Reactive Protein (CRP). (If CRP was missing then Erythrocyte Sedimentation Rate (ESR) was used if available.)
- measure
- Percentage of Participants With American College of Rheumatology (ACR) ACR70 Response at Week 52
- time Frame
- Baseline, Week 52
- 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. Remission is defined as achieving a DAS28-ESR score of less than 2.6
- measure
- Percentage of Participants With DAS28-ESR Remission at Week 52
- time Frame
- Week 52
Full study description
- brief Summary
- This is a phase III, randomized, controlled, double-blind, parallel group, international study in approximately 750 patients with active Rheumatoid Arthritis (RA) who are naive to Methotrexate (MTX) therapy. Rheumatoid Factor (RF)-positive and RF-negative patients will be enrolled and will be allocated equally between 3 treatment arms.
Source references
- references
- citation
- Tak PP, Rigby W, Rubbert-Roth A, Peterfy C, van Vollenhoven RF, Stohl W, Healy E, Hessey E, Reynard M, Shaw T. Sustained inhibition of progressive joint damage with rituximab plus methotrexate in early active rheumatoid arthritis: 2-year results from the randomised controlled trial IMAGE. Ann Rheum Dis. 2012 Mar;71(3):351-7. doi: 10.1136/annrheumdis-2011-200170. Epub 2011 Oct 19.
- pmid
- 22012969
- type
- DERIVED
- citation
- Rigby W, Ferraccioli G, Greenwald M, Zazueta-Montiel B, Fleischmann R, Wassenberg S, Ogale S, Armstrong G, Jahreis A, Burke L, Mela C, Chen A. Effect of rituximab on physical function and quality of life in patients with rheumatoid arthritis previously untreated with methotrexate. Arthritis Care Res (Hoboken). 2011 May;63(5):711-20. doi: 10.1002/acr.20419.
- pmid
- 21557525
- type
- DERIVED
- citation
- Tak PP, Rigby WF, Rubbert-Roth A, Peterfy CG, van Vollenhoven RF, Stohl W, Hessey E, Chen A, Tyrrell H, Shaw TM; IMAGE Investigators. Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial. Ann Rheum Dis. 2011 Jan;70(1):39-46. doi: 10.1136/ard.2010.137703. Epub 2010 Oct 11.
- pmid
- 20937671
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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Preserved source evidence · Not medical advice