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Study was terminated after enrollment of 3 participants due to recruitment difficulties.
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This single arm study will investigate the pattern of B cell depletion in synovial tissue and peripheral blood of patients with active RA, after MabThera (1000mg iv x 2 on days 1 and 15) + methotrexate (10-25mg/week po) treatment. The clinical efficacy and pharmacokinetic profile of MabThera after treatment and retreatment will also be investigated. The anticipated time on study treatment is 2+ years, and the target sample size is <100 individuals.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rituximab [MabThera/Rituxan] | Drug | 1000mg iv on days 1 and 15 |
| |
| Methotrexate |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Absolute B Cell Cluster Differential 19 Positive (CD19+) Counts in Synovial Tissues | The change from baseline in absolute B cell (CD19+) counts at each visit calculated as (B cell count at visit minus B cell count at baseline) for synovial tissues. | Weeks 12, 24, and 36 |
| Change From Baseline in Absolute B Cell CD19+ Counts in Peripheral Blood | The change from baseline in absolute B cell (CD19+) count at each visit calculated as (B cell count at visit minus B cell count at baseline) for peripheral blood. | Weeks 4, 12, 24, 36, and 48 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Absolute Counts of Cells Expressing CD20+ and CD22+ in Absolute B Cell (CD19+) Counts in Synovial Tissues | The change in absolute counts of cells expressing the key B cell markers (CD20+ and CD22+) in absolute B cell (CD19+) counts in synovial tissues at Weeks 12, 24, and 36, relative to baseline. | Weeks 12, 24, and 36 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Amsterdam | 1105 AZ | Netherlands |
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| ID | Title | Description |
|---|---|---|
| FG000 | Rituximab + Methotrexate (MTX) | Participants received rituximab 1000 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 and also on Days 169 and 183 (for those meeting retreatment criteria) or as needed (PRN) if retreatment criteria were not met; premedication with methylprednisolone (MP) 100 mg IV was administered at least 30 minutes prior to each rituximab infusion. Participants also received MTX 10-25 mg per week (mg/week; oral or parenteral) for up to 48 weeks and folate (greater than or equal to [≥]5 mg/week) given as either a single weekly dose or as divided dose for up to 48 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Rituximab + MTX | Participants received rituximab 1000 mg via IV infusion on Days 1 and 15 and also on Days 169 and 183 (for those meeting retreatment criteria) or PRN if retreatment criteria were not met; premedication with MP 100 mg IV was administered at least 30 minutes prior to each rituximab infusion. Participants also received MTX 10-25 mg/week (oral or parenteral) for up to 48 weeks and folate (≥5 mg/week) given as either a single weekly dose or as divided dose for up to 48 weeks. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Absolute B Cell Cluster Differential 19 Positive (CD19+) Counts in Synovial Tissues | The change from baseline in absolute B cell (CD19+) counts at each visit calculated as (B cell count at visit minus B cell count at baseline) for synovial tissues. | No participant data were analyzed. Study was terminated after enrollment of 3 participants as it was decided that it would not be appropriate to expose further participants to study drug since the objectives and data sought from this study had been published from other, independent sources and given the recruitment difficulties encountered. | Posted | Weeks 12, 24, and 36 |
|
Not provided
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Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Rituximab + MTX | Participants received rituximab 1000 mg via IV infusion on Days 1 and 15 and also on Days 169 and 183 (for those meeting retreatment criteria) or PRN if retreatment criteria were not met; premedication with MP 100 mg IV was administered at least 30 minutes prior to each rituximab infusion. Participants also received MTX 10-25 mg/week (oral or parenteral) for up to 48 weeks and folate (≥5 mg/week) given as either a single weekly dose or as divided dose for up to 48 weeks. |
Not provided
Not provided
Study terminated after enrollment of 3 participants due to recruitment difficulties and since the objectives and data under study had been published from other, independent sources it was not appropriate to expose further participants to study drug.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications Organization | Hoffmann-LaRoche | 800-821-8590 | genentech@druginfo.com |
| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000069283 | Rituximab |
| D008727 | Methotrexate |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| Drug |
10-25mg po weekly |
|
| Change From Baseline in Absolute Counts of Cells Expressing CD20+ and CD22+ in Absolute B Cell (CD19+) Counts in Peripheral Blood | The change in absolute counts of cells expressing the key B cell markers (CD20+ and CD22+) in absolute B cell (CD19+) counts in peripheral blood at Weeks 4,12, 24, 36, and 48, relative to baseline. | Weeks 4,12, 24, 36, and 48 |
| Change From Baseline in Levels of Key Cytokines (Interleukin [IL]-1beta [β], Tumor Necrosis Factor [TNF]-Alpha [α], IL-4, IL-6, IL-10, and IL-13) in Blood (Serum) | The change in levels of key cytokines (IL-1β, TNF-α, IL-4, IL-6, IL-10, and IL-13) in blood (serum) on Days 15 and 183 and at Weeks 4, 12, 24, 36, and 48, relative to baseline. | Days 15 and 183 and Weeks 4, 12, 24, 36, and 48 |
| Change From Baseline in Levels of Key Cytokines in (IL-1β, TNF-α, IL-6, and IL-10) in Synovial Tissues | The change in levels of key cytokines in (IL-1β, TNF-α, IL-6, and IL-10) in synovial tissues at Weeks 12, 24, and 36, relative to baseline. | Weeks 12, 24, and 36 |
| Change From Baseline in Myelocytomatosis Oncogene (C-myc) and BCL2-associated X Protein (BAX) in Peripheral Blood | The change in ribonucleic acid (RNA) expression of markers of apoptosis (C-myc and BAX) in peripheral blood at Days 15 and 183, relative to baseline. | Days 15 and 183 |
| Percentage of Participants Achieving American College of Rheumatology 20 Percent (20%) 50%, and 70% (ACR20/50/70) Response | ACR20/50/70 response is greater than or equal to (≥) 20%, 50%, or 70% improvement, respectively, in tender joint count (TJC) and swollen joint count (SJC); and improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP). | Week 48 |
| Change From Baseline in Disease Activity Score Based on 28 Joint Count (DAS28) Erythrocyte Sedimentation Rate (ESR) Score | The change in DAS28-ESR at Weeks 12, 24, 36, and 48, relative to baseline. DAS28-ESR was calculated from SJC and TJC using 28-joint count, ESR (millimeters per hour [mm/hour]) and patient global assessment of disease activity (participant-rated arthritis activity assessment). Total score range: 0-9.4, higher score equals (=) more disease activity. DAS28-ESR less than or equal to (≤) 3.2 implied low disease activity and greater than (>)3.2 to 5.1 implied moderate to high disease activity, and DAS28-ESR <2.6 = remission. | Weeks 12, 24, 36, and 48 |
| Percentage of Participants Achieving Response by European League Against Rheumatism (EULAR) Category | The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline >1.2 with DAS28 ≤ 3.2; moderate responders: change from baseline >1.2 with DAS28 >3.2 to ≤ 5.1 or change from baseline >0.6 to ≤ 1.2 with DAS28 ≤ 5.1; non-responders: change from baseline ≤ 0.6 or change from baseline >0.6 and ≤ 1.2 with DAS28 >5.1. | Weeks 24, 36, and 48 |
| Change From Baseline in ACR Core Set | The changes from baseline in the ACR core set parameters at Week 48. Change from baseline to Week 48 over time in ACR core set: SJC, TJC, physician's global assessment of disease activity, patient's global assessment of disease activity, patient's assessment of pain, HAQ, ESR, and CRP. ACR20/50/70 response: ≥20%/50%/70% improvement in SJC; ≥20%/50%/70% improvement in TJC; and ≥20%/50%/70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; physician's global assessment of disease activity, participant's assessment of disease activity, participant assessment of functional disability via a HAQ, and CRP at each visit. | Week 48 |
| Change From Baseline in Modified Total Sharp Score (mTSS) | mTSS = sum of erosion and Joint Space Narrowing (JSN) scores for 44 joints (16 per hand and 6 per foot). mTSS scores ranged from 0 (normal) to 448 (worst possible total score). Change: scores at observation minus score at baseline. An increase in mTSS from baseline. An increase in mTSS from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement. | Weeks 24 and 48 |
| Change From Baseline in Erosion Score | Changes from baseline in modified Sharp radiographic erosion score from baseline to Weeks 24 and 48. The change in score at week X (where X=Week 24 or Week 48, as appropriate) calculated as: Change = week X score minus screening score. | Weeks 24 and 48 |
| Change From Baseline in Joint Space Narrowing (JSN) Score | Changes from baseline in modified Sharp radiographic JSN score from baseline to Weeks 24 and 48. The change in score at week X (where X=Week 24 or Week 48, as appropriate) calculated as: Change = week X score minus screening score. | Weeks 24 and 48 |
| years |
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
| Secondary | Change From Baseline in Absolute Counts of Cells Expressing CD20+ and CD22+ in Absolute B Cell (CD19+) Counts in Synovial Tissues | The change in absolute counts of cells expressing the key B cell markers (CD20+ and CD22+) in absolute B cell (CD19+) counts in synovial tissues at Weeks 12, 24, and 36, relative to baseline. | No participant data were analyzed. Study was terminated after enrollment of 3 participants as it was decided that it would not be appropriate to expose further participants to study drug since the objectives and data sought from this study had been published from other, independent sources and given the recruitment difficulties encountered. | Posted | Weeks 12, 24, and 36 |
|
|
| Secondary | Change From Baseline in Absolute Counts of Cells Expressing CD20+ and CD22+ in Absolute B Cell (CD19+) Counts in Peripheral Blood | The change in absolute counts of cells expressing the key B cell markers (CD20+ and CD22+) in absolute B cell (CD19+) counts in peripheral blood at Weeks 4,12, 24, 36, and 48, relative to baseline. | No participant data were analyzed. Study was terminated after enrollment of 3 participants as it was decided that it would not be appropriate to expose further participants to study drug since the objectives and data sought from this study had been published from other, independent sources and given the recruitment difficulties encountered. | Posted | Weeks 4,12, 24, 36, and 48 |
|
|
| Secondary | Change From Baseline in Levels of Key Cytokines (Interleukin [IL]-1beta [β], Tumor Necrosis Factor [TNF]-Alpha [α], IL-4, IL-6, IL-10, and IL-13) in Blood (Serum) | The change in levels of key cytokines (IL-1β, TNF-α, IL-4, IL-6, IL-10, and IL-13) in blood (serum) on Days 15 and 183 and at Weeks 4, 12, 24, 36, and 48, relative to baseline. | No participant data were analyzed. Study was terminated after enrollment of 3 participants as it was decided that it would not be appropriate to expose further participants to study drug since the objectives and data sought from this study had been published from other, independent sources and given the recruitment difficulties encountered. | Posted | Days 15 and 183 and Weeks 4, 12, 24, 36, and 48 |
|
|
| Secondary | Change From Baseline in Levels of Key Cytokines in (IL-1β, TNF-α, IL-6, and IL-10) in Synovial Tissues | The change in levels of key cytokines in (IL-1β, TNF-α, IL-6, and IL-10) in synovial tissues at Weeks 12, 24, and 36, relative to baseline. | No participant data were analyzed. Study was terminated after enrollment of 3 participants as it was decided that it would not be appropriate to expose further participants to study drug since the objectives and data sought from this study had been published from other, independent sources and given the recruitment difficulties encountered. | Posted | Weeks 12, 24, and 36 |
|
|
| Secondary | Change From Baseline in Myelocytomatosis Oncogene (C-myc) and BCL2-associated X Protein (BAX) in Peripheral Blood | The change in ribonucleic acid (RNA) expression of markers of apoptosis (C-myc and BAX) in peripheral blood at Days 15 and 183, relative to baseline. | No participant data were analyzed. Study was terminated after enrollment of 3 participants as it was decided that it would not be appropriate to expose further participants to study drug since the objectives and data sought from this study had been published from other, independent sources and given the recruitment difficulties encountered. | Posted | Days 15 and 183 |
|
|
| Secondary | Percentage of Participants Achieving American College of Rheumatology 20 Percent (20%) 50%, and 70% (ACR20/50/70) Response | ACR20/50/70 response is greater than or equal to (≥) 20%, 50%, or 70% improvement, respectively, in tender joint count (TJC) and swollen joint count (SJC); and improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP). | No participant data were analyzed. Study was terminated after enrollment of 3 participants as it was decided that it would not be appropriate to expose further participants to study drug since the objectives and data sought from this study had been published from other, independent sources and given the recruitment difficulties encountered. | Posted | Week 48 |
|
|
| Secondary | Change From Baseline in Disease Activity Score Based on 28 Joint Count (DAS28) Erythrocyte Sedimentation Rate (ESR) Score | The change in DAS28-ESR at Weeks 12, 24, 36, and 48, relative to baseline. DAS28-ESR was calculated from SJC and TJC using 28-joint count, ESR (millimeters per hour [mm/hour]) and patient global assessment of disease activity (participant-rated arthritis activity assessment). Total score range: 0-9.4, higher score equals (=) more disease activity. DAS28-ESR less than or equal to (≤) 3.2 implied low disease activity and greater than (>)3.2 to 5.1 implied moderate to high disease activity, and DAS28-ESR <2.6 = remission. | No participant data were analyzed. Study was terminated after enrollment of 3 participants as it was decided that it would not be appropriate to expose further participants to study drug since the objectives and data sought from this study had been published from other, independent sources and given the recruitment difficulties encountered. | Posted | Weeks 12, 24, 36, and 48 |
|
|
| Secondary | Percentage of Participants Achieving Response by European League Against Rheumatism (EULAR) Category | The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline >1.2 with DAS28 ≤ 3.2; moderate responders: change from baseline >1.2 with DAS28 >3.2 to ≤ 5.1 or change from baseline >0.6 to ≤ 1.2 with DAS28 ≤ 5.1; non-responders: change from baseline ≤ 0.6 or change from baseline >0.6 and ≤ 1.2 with DAS28 >5.1. | No participant data were analyzed. Study was terminated after enrollment of 3 participants as it was decided that it would not be appropriate to expose further participants to study drug since the objectives and data sought from this study had been published from other, independent sources and given the recruitment difficulties encountered. | Posted | Weeks 24, 36, and 48 |
|
|
| Secondary | Change From Baseline in ACR Core Set | The changes from baseline in the ACR core set parameters at Week 48. Change from baseline to Week 48 over time in ACR core set: SJC, TJC, physician's global assessment of disease activity, patient's global assessment of disease activity, patient's assessment of pain, HAQ, ESR, and CRP. ACR20/50/70 response: ≥20%/50%/70% improvement in SJC; ≥20%/50%/70% improvement in TJC; and ≥20%/50%/70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; physician's global assessment of disease activity, participant's assessment of disease activity, participant assessment of functional disability via a HAQ, and CRP at each visit. | No participant data were analyzed. Study was terminated after enrollment of 3 participants as it was decided that it would not be appropriate to expose further participants to study drug since the objectives and data sought from this study had been published from other, independent sources and given the recruitment difficulties encountered. | Posted | Week 48 |
|
|
| Secondary | Change From Baseline in Modified Total Sharp Score (mTSS) | mTSS = sum of erosion and Joint Space Narrowing (JSN) scores for 44 joints (16 per hand and 6 per foot). mTSS scores ranged from 0 (normal) to 448 (worst possible total score). Change: scores at observation minus score at baseline. An increase in mTSS from baseline. An increase in mTSS from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement. | No participant data were analyzed. Study was terminated after enrollment of 3 participants as it was decided that it would not be appropriate to expose further participants to study drug since the objectives and data sought from this study had been published from other, independent sources and given the recruitment difficulties encountered. | Posted | Weeks 24 and 48 |
|
|
| Secondary | Change From Baseline in Erosion Score | Changes from baseline in modified Sharp radiographic erosion score from baseline to Weeks 24 and 48. The change in score at week X (where X=Week 24 or Week 48, as appropriate) calculated as: Change = week X score minus screening score. | No participant data were analyzed. Study was terminated after enrollment of 3 participants as it was decided that it would not be appropriate to expose further participants to study drug since the objectives and data sought from this study had been published from other, independent sources and given the recruitment difficulties encountered. | Posted | Weeks 24 and 48 |
|
|
| Secondary | Change From Baseline in Joint Space Narrowing (JSN) Score | Changes from baseline in modified Sharp radiographic JSN score from baseline to Weeks 24 and 48. The change in score at week X (where X=Week 24 or Week 48, as appropriate) calculated as: Change = week X score minus screening score. | No participant data were analyzed. Study was terminated after enrollment of 3 participants as it was decided that it would not be appropriate to expose further participants to study drug since the objectives and data sought from this study had been published from other, independent sources and given the recruitment difficulties encountered. | Posted | Weeks 24 and 48 |
|
|
| Primary | Change From Baseline in Absolute B Cell CD19+ Counts in Peripheral Blood | The change from baseline in absolute B cell (CD19+) count at each visit calculated as (B cell count at visit minus B cell count at baseline) for peripheral blood. | No participant data were analyzed. Study was terminated after enrollment of 3 participants as it was decided that it would not be appropriate to expose further participants to study drug since the objectives and data sought from this study had been published from other, independent sources and given the recruitment difficulties encountered. | Posted | Weeks 4, 12, 24, 36, and 48 |
|
|
| 0 |
| 0 |
| 0 |
| 0 |
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
| D003240 |
| Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D000630 | Aminopterin |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |