Rheumatoid ArthritisPhase 3IMAGENCT00299104
A Study to Evaluate Rituximab in Combination With Methotrexate in Methotrexate-Naive Patients With Active Rheumatoid Arthritis
A Phase 3 study testing folate, methotrexate and methylprednisolone in people with Rheumatoid Arthritis, run by Genentech, Inc..
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 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
- 755 participants
- Where
- No sites listed yet
- Study dates
- Jan 2006to Jul 2013
- Phase
- Phase 3
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
About this study
Official title: A Randomized, Phase 3, Controlled, Double-Blind, Parallel-Group, Multicenter Study to Evaluate the Safety and Efficacy of Rituximab in Combination With Methotrexate (MTX) Compared to MTX Alone, in Methotrexate-Naive Patients With Active Rheumatoid Arthritis
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.
- Conditions
- Rheumatoid Arthritis
- Being tested
- folate, methotrexate, methylprednisolone, placebo, rituximab
- Keywords
- Rituxan, MTX, RA, IMAGE, WA17047
- 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
Intravenous repeating dose
methotrexateDrug
Oral or parenteral repeating dose
Intravenous repeating dose
placeboDrug
Intravenous repeating dose
rituximabDrug
Intravenous repeating dose
| Study group | Role | What they receive |
|---|---|---|
| Rituximab (0.5 g x 2) + Methotrexate | Experimental | 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 Receives: Drug: folate; Drug: methotrexate; Drug: methylprednisolone; Drug: rituximab |
| Rituximab (1.0 g x 2) + Methotrexate | Experimental | 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 Receives: Drug: folate; Drug: methotrexate; Drug: methylprednisolone; Drug: rituximab |
| Placebo + Methotrexate | Placebo comparator | 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. Receives: Drug: folate; Drug: methotrexate; Drug: methylprednisolone; Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Modified Total Sharp Score (mTSS) From Screening at Week 52
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.
Measured: Baseline and week 52
Secondary outcomes (29)
Change From Baseline in Modified Sharp Erosion Score at Week 52
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.
Measured: Baseline and week 52
Percentage of Patients Without Radiographic Progression at Week 52
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.
Measured: Baseline, Week 52
Percentage of Patients Without Radiographic Progression in Total Erosion Score at Week 52
No radiographic progression is defined as a change in the total erosion score at Week 52 of less than or equal to zero.
Measured: Baseline, Week 52
Change From Baseline in Modified Joint Space Narrowing (JSN) Score at Week 52
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.
Measured: Baseline and week 52
Change From Baseline in the Modified Total Sharp Score at Week 24
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.
Measured: Baseline, Week 24
Change From Baseline in the Total Erosion Score at Week 24
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.
Measured: Baseline, Week 24
Change From Baseline in Modified Joint Space Narrowing (JSN) Score at Week 24
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.
Measured: Baseline, Week 24
Percentage of Participants Without Radiographic Progression at Week 24
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.
Measured: Baseline, Week 24
Percentage of Participants With American College of Rheumatology (ACR) ACR50 Response at Week 52
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.)
Measured: Week 52
Change From Baseline in the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 52
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).
Measured: Baseline, Week 52
Percentage of Participants With American College of Rheumatology (ACR) ACR70 Response at Week 52
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.)
Measured: Baseline, Week 52
Percentage of Participants With DAS28-ESR Remission at Week 52
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
Measured: Week 52
Percentage of Participants With European League Against Rheumatism (EULAR) Good Response at Week 52
European League Against Rheumatism (EULAR) criteria reflects an improvement in disease activity and an attainment of a lower degree of disease activity. A good response is defined as an improvement in the DAS28-ESR of > 1.2 compared with baseline, and attainment of a DAS28-ESR of < 3.2.
Measured: Baseline, Week 52
The Percentage of Participants With Major Clinical Response at Week 52
Major clinical response is defined as a continuous six-month period of success by the ACR70.
ACR70= 70% improvement compared with baseline in both Total Joint Count and Swollen Joint Count, as well as a 70% improvement in 3 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.)
Measured: Week 52
Percentage of Participants With DAS28-ESR Low Disease Activity at Week 52
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.
Low disease activity is defined as achieving a DAS28-ESR score of less than or equal to 3.2
Measured: Week 52
Percentage of Participants With American College of Rheumatology (ACR) ACR20 Response at Week 52
To achieve an ACR20 response requires at least a 20% improvement compared with baseline in both Total Joint Count and Swollen Joint Count, as well as a 20% 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.)
Measured: Baseline, Week 52
Percentage of Participants With American College of Rheumatology (ACR) ACR90 Response at Week 52
To achieve an ACR90 response requires at least a 90% improvement compared with baseline in both Total Joint Count and Swollen Joint Count, as well as a 90% 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.)
Measured: Baseline, Week 52
Change in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Score From Baseline at Week 52
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, Week 52
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 52
The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip,and common daily activities. Each domain has at least two component questions. There are four possible responses for each component ranging from 0(without any difficulty) to 4 (unable to do).HAQ-DI=sum of worst scores in each domain divided by the number of domains answered. A negative change from baseline indicates improvement.
Measured: Baseline, Week 52
Change From Baseline in the SF-36 Physical Health Component Summary Score at Week 52 and Week 104
The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. 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. A positive change from baseline indicates improvement.
Means are adjusted for baseline value, Rheumatoid Factor status and region.
Measured: Baseline, Week 52, Week 104
Change From Baseline in the SF-36 Mental Health Component Summary Score at Week 52 and Week 104
The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. 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. A positive change from baseline indicates improvement.
Means are adjusted for baseline value, Rheumatoid Factor status and region.
Measured: Baseline, Weeks 52, Week 104
Percentage of Participants With Categorical Change in Health Assessment Questionnaire- Disability Index (HAQ-DI) From Baseline at Week 52
The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. Each domain has at least two component questions. There are four possible responses for each component on a scale of 0 (without difficulty) to 3 (unable to do). Higher scores=greater dysfunction.
Improved:HAQ-DI score change <=-0.22 Unchanged:HAQ-DI score change -0.22 to 0.22 Worsened:HAQ score => 0.22
Measured: Baseline, Week 52
Percentage of Patients With Minimally Clinically Important Difference (MCID) in the SF-36 Physical Health Component Score at Week 52
MCID is defined as a change from baseline in SF-36 Physical Health Component Score of >5.42.
SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. 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. A positive change from baseline indicates improvement.
Measured: Baseline, Week 52
Percentage of Patients With Minimally Clinically Important Difference (MCID) in the SF-36 Mental Health Component Score at Week 52
MCID is defined as a change from baseline in SF-36 Mental Health Component Score of >6.33.
SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. 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. A positive change from baseline indicates improvement.
Measured: Baseline, Week 52
Change From Baseline in the Modified Total Sharp Score at Week 104
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.
Measured: Baseline, Week 104
Change From Baseline in the Total Erosion Score at Week 104
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 change from the score at baseline to week 104 is calculated.
Measured: Baseline, Week 104
Percentage of Participants Without Radiographic Progression at Week 104
Percentage of patients without radiographic progression at Week 104, 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.
Measured: Baseline, Week 104
Percentage of Participants Without Radiographic Progression in the Total Erosion Score at Week 104
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 score at baseline is compared to the score at week 104.
No progression is defined as a change from score at screening to week 104 ≤0.
Measured: Week 104
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 104
The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Each domain has at least two component questions. There are four possible responses for each component ranging from 0(without any difficulty) to 4 (unable to do). HAQ-DI=sum of worst scores in each domain divided by the number of domains answered. A negative change from baseline indicates improvement.
Measured: Baseline, Week 104
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2006 (estimated)
- Study startJan 2006
- Primary completionSep 2008
- Study completionJul 2013
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.
- Publications (3)Papers the sponsor has linked to this study.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 755 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genentech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Hoffmann-La Roche
- Responsible party
- Sponsor
- Investigators
- Arndt Schottelius, M.D., Study director, Genentech, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00299104
- Sponsor's protocol ID
- U3373g
- Other IDs
- WA17047
- Acronym
- IMAGE
- Status last verified
- Jun 2017
- First submitted
- 2 Mar 2006
- Last updated
- 28 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 22012969Rigby 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.
PubMed 21557525Tak 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.
PubMed 20937671
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Phase 3, Controlled, Double-Blind, Parallel-Group, Multicenter Study to Evaluate the Safety and Efficacy of Rituximab in Combination With Methotrexate (MTX) Compared to MTX Alone, in Methotrexate-Naive Patients With Active Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT00299104
- Acronym / sponsor ID
- IMAGE / U3373g
- Conditions
- Rheumatoid Arthritis
- Keywords
- Rituxan, MTX, RA, IMAGE, WA17047
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 755 participants (actual)
- Lead sponsor
- Genentech, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Hoffmann-La Roche
- Study start
- Jan 2006
- Primary completion
- Sep 2008 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 6 Mar 2006 (estimated)
- Results
- Posted 10 Aug 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Rituximab (0.5 g x 2) + Methotrexate | Experimental | Drug: folate, Drug: methotrexate, Drug: methylprednisolone, Drug: rituximabRituximab 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 |
| Rituximab (1.0 g x 2) + Methotrexate | Experimental | Drug: folate, Drug: methotrexate, Drug: methylprednisolone, Drug: rituximabRituximab 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 |
| Placebo + Methotrexate | Placebo comparator | Drug: folate, Drug: methotrexate, Drug: methylprednisolone, Drug: placeboPlacebo 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (6 listed)
- 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
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 |
|---|---|---|
| folateIntravenous repeating dose | Drug | Placebo + Methotrexate, Rituximab (0.5 g x 2) + Methotrexate, Rituximab (1.0 g x 2) + Methotrexate |
| methotrexateOral or parenteral repeating dose | Drug | Placebo + Methotrexate, Rituximab (0.5 g x 2) + Methotrexate, Rituximab (1.0 g x 2) + Methotrexate |
| methylprednisoloneIntravenous repeating dose | Drug | Placebo + Methotrexate, Rituximab (0.5 g x 2) + Methotrexate, Rituximab (1.0 g x 2) + Methotrexate |
| placeboIntravenous repeating dose | Drug | Placebo + Methotrexate |
| rituximabIntravenous repeating dose | Drug | Rituximab (0.5 g x 2) + Methotrexate, Rituximab (1.0 g x 2) + Methotrexate |
Primary outcome
Change From Baseline in Modified Total Sharp Score (mTSS) From Screening at Week 52
Time frame: Baseline and week 52
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.
29 secondary outcomes
Change From Baseline in Modified Sharp Erosion Score at Week 52
Time frame: Baseline and week 52
Percentage of Patients Without Radiographic Progression at Week 52
Time frame: Baseline, Week 52
Percentage of Patients Without Radiographic Progression in Total Erosion Score at Week 52
Time frame: Baseline, Week 52
Change From Baseline in Modified Joint Space Narrowing (JSN) Score at Week 52
Time frame: Baseline and week 52
Change From Baseline in the Modified Total Sharp Score at Week 24
Time frame: Baseline, Week 24
Change From Baseline in the Total Erosion Score at Week 24
Time frame: Baseline, Week 24
Change From Baseline in Modified Joint Space Narrowing (JSN) Score at Week 24
Time frame: Baseline, Week 24
Percentage of Participants Without Radiographic Progression at Week 24
Time frame: Baseline, Week 24
Percentage of Participants With American College of Rheumatology (ACR) ACR50 Response at Week 52
Time frame: Week 52
Change From Baseline in the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 52
Time frame: Baseline, Week 52
Percentage of Participants With American College of Rheumatology (ACR) ACR70 Response at Week 52
Time frame: Baseline, Week 52
Percentage of Participants With DAS28-ESR Remission at Week 52
Time frame: Week 52
Percentage of Participants With European League Against Rheumatism (EULAR) Good Response at Week 52
Time frame: Baseline, Week 52
The Percentage of Participants With Major Clinical Response at Week 52
Time frame: Week 52
Percentage of Participants With DAS28-ESR Low Disease Activity at Week 52
Time frame: Week 52
Percentage of Participants With American College of Rheumatology (ACR) ACR20 Response at Week 52
Time frame: Baseline, Week 52
Percentage of Participants With American College of Rheumatology (ACR) ACR90 Response at Week 52
Time frame: Baseline, Week 52
Change in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Score From Baseline at Week 52
Time frame: Baseline, Week 52
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 52
Time frame: Baseline, Week 52
Change From Baseline in the SF-36 Physical Health Component Summary Score at Week 52 and Week 104
Time frame: Baseline, Week 52, Week 104
Change From Baseline in the SF-36 Mental Health Component Summary Score at Week 52 and Week 104
Time frame: Baseline, Weeks 52, Week 104
Percentage of Participants With Categorical Change in Health Assessment Questionnaire- Disability Index (HAQ-DI) From Baseline at Week 52
Time frame: Baseline, Week 52
Percentage of Patients With Minimally Clinically Important Difference (MCID) in the SF-36 Physical Health Component Score at Week 52
Time frame: Baseline, Week 52
Percentage of Patients With Minimally Clinically Important Difference (MCID) in the SF-36 Mental Health Component Score at Week 52
Time frame: Baseline, Week 52
Change From Baseline in the Modified Total Sharp Score at Week 104
Time frame: Baseline, Week 104
Change From Baseline in the Total Erosion Score at Week 104
Time frame: Baseline, Week 104
Percentage of Participants Without Radiographic Progression at Week 104
Time frame: Baseline, Week 104
Percentage of Participants Without Radiographic Progression in the Total Erosion Score at Week 104
Time frame: Week 104
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 104
Time frame: Baseline, Week 104
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22012969Tak 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.
- Derived from this study: PubMed 21557525Rigby 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.
- Derived from this study: PubMed 20937671Tak 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.
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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.
Arndt Schottelius, M.D. study director
Genentech, Inc.
Questions about this trial
What is this clinical trial studying?
A Phase 3 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 6 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 28 Jul 2017. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 10 Aug 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?
Change From Baseline in Modified Total Sharp Score (mTSS) From Screening at Week 52 (time frame: Baseline and week 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00299104, which also lists 3 linked publications.
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 28 Jul 2017.