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In this open-label single arm study the safety and efficacy of Mabthera will be evaluated in patients with active rheumatoid arthritis who have had an inadequate response to methotrexate. Patients will receive MabThera (1000mg iv infusion) on days 1 and 15, and background methotrexate (10-25mg po or sc weekly). After the initial study period of 24 weeks, eligible patients may receive up to 3 re-treatments with MabThera. The anticipated time on study treatment is 1-2 years and target sample size is <50
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| single arm | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rituximab [MabThera/Rituxan] | Drug | 1000 mg iv infusion on days 1 and 15 |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Reporting Adverse Events (AEs) | Days 1 and 15, every 8 weeks up to Week 24 and and then every 3 months up to 18 months for a total of 104 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage Change in Disease Activity Score 28 (DAS28) From Baseline to Week 24 | The DAS28 score is a measure of the participant's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], participant's global assessment of disease activity [visual analog scale: [VAS] 0 equals (=) no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to 10. Scores less than (<) 2.6 indicate best disease control and scores greater than or equal to (≥) 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6. The average improvement at each visit to the group score is equal to the formula (Previous DAS28 minus [-] current DAS 28)/ Previous DAS 28 x 100. Negative percentages indicate that the participant has worsened in comparison to last evaluation, and positive percentages indicate improvement of its DAS28 score and correlated with a bettering of clinical situation. |
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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 |
|---|---|---|---|---|---|---|
| Hopital Farhat Hached; Service Rhumatologie | Sousse | 4000 | Tunisia | |||
| Hopital Charles Nicole; Service Rhumatologie |
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| ID | Title | Description |
|---|---|---|
| FG000 | Rituximab | Participants received rituximab 1000 milligrams (mg) intravenous (iv) infusion on Days 1 and 15 along with methotrexate 10-25 mg weekly, orally or parenterally. Participants could receive concomitant treatment with corticosteroids (less than or equal to [≤] 10 milligrams per day (mg/day) prednisone or equivalent) or intra-articular corticosteroids, non-steroid anti-inflammatory drugs (NSAIDs) and analgesics throughout the study period at the discretion of the investigator. All participants received methylprednisolone100 mg iv prior to each rituximab infusion. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Intent-to-Treat (ITT) population: All participants who received any part of an infusion have been included in the ITT analysis. Participants who prematurely withdrew from the study for any reason and for whom an assessment was not performed for whatever reason, were still included in the ITT analyses.
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| ID | Title | Description |
|---|---|---|
| BG000 | Rituximab | Participants received rituximab 1000 mg iv infusion on Days 1 and 15 along with methotrexate 10-25 mg weekly, orally or parenterally. Participants could receive concomitant treatment with corticosteroids (≤ 10 mg/day prednisone or equivalent) or intra-articular corticosteroids, NSAIDs and analgesics throughout the study period at the discretion of the investigator. All participants received methylprednisolone 100 mg iv prior to each rituximab infusion. |
| 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 | Number of Participants Reporting Adverse Events (AEs) | Safety Population: Included all participants who have received any part of an infusion of study medication. | Posted | Number | number of participants | Days 1 and 15, every 8 weeks up to Week 24 and and then every 3 months up to 18 months for a total of 104 weeks |
|
AEs were recorded from the day of first infusion until the End of Study at 104 weeks.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Rituximab | Participants received rituximab 1000 mg iv infusion on Days 1 and 15 along with methotrexate 10-25 mg weekly, orally or parenterally. Participants could receive concomitant treatment with corticosteroids (≤ 10 mg/day prednisone or equivalent) or intra-articular corticosteroids, NSAIDs and analgesics throughout the study period at the discretion of the investigator. All participants received methylprednisolone 100 mg iv prior to each rituximab infusion. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | CTCAE (Unspecified) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Blurred Vision | Eye disorders | CTCAE (Unspecified) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann- LaRoche | 800-821-8590 | genentech@druginfo.com |
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| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
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| ID | Term |
|---|---|
| D000069283 | Rituximab |
| D008727 | Methotrexate |
| D008775 | Methylprednisolone |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| methotrexate |
| Drug |
10-25 mg weekly (oral or parenteral) |
|
| methylprednisolone | Drug | 100 mg iv prior to each rituximab infusion |
|
| Baseline and Week 24 |
| Percentage of Participants Whose DAS28 Improved by >1.2 at Week 24 | The DAS28 score is a measure of the participant's disease activity calculated using the TJC [28 joints], SJC [28 joints], participant's global assessment of disease activity [VAS: 0 = no disease activity to 100 = maximum disease activity] and the ESR for a total possible score of 0 to 10. Scores < 2.6 indicate best disease control and scores ≥ 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6. An improvement of >1.2 was considered to be clinically significant improvement. | Baseline and Week 24 |
| Change in Bone Density (in Participants Untreated With Bisphosphonates) | Bone mineral density test was performed using x-ray radiation and the values of bone density were provided directly by the apparatus as grams per square centimeter (g/cm^2) . T-score is the number of standard deviations above or below the mean for a healthy 30 year old adult of the same sex and ethnicity as the participant. A T-score with above -1 is normal bone density level. A T-score between -1 and -2.5 means that the bone density is below normal and it might be a sign of an osteopenia and may also lead into osteoporosis. A T-score below -2.5 indicates osteoporosis. | Screening and Week 84 |
| Tunis |
| 1006 |
| Tunisia |
| Hopital La Rabta; Service Rhumatologie | Tunis | 1007 | Tunisia |
| Hopital Mongi Slim; Service Rhumatologie | Tunis | 2046 | Tunisia |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Secondary | Percentage Change in Disease Activity Score 28 (DAS28) From Baseline to Week 24 | The DAS28 score is a measure of the participant's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], participant's global assessment of disease activity [visual analog scale: [VAS] 0 equals (=) no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to 10. Scores less than (<) 2.6 indicate best disease control and scores greater than or equal to (≥) 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6. The average improvement at each visit to the group score is equal to the formula (Previous DAS28 minus [-] current DAS 28)/ Previous DAS 28 x 100. Negative percentages indicate that the participant has worsened in comparison to last evaluation, and positive percentages indicate improvement of its DAS28 score and correlated with a bettering of clinical situation. | ITT population; Only participants with DAS28 values at both Baseline and Week 24 were included in the analysis. | Posted | Mean | Standard Deviation | percentage change from baseline | Baseline and Week 24 |
|
|
|
| Secondary | Percentage of Participants Whose DAS28 Improved by >1.2 at Week 24 | The DAS28 score is a measure of the participant's disease activity calculated using the TJC [28 joints], SJC [28 joints], participant's global assessment of disease activity [VAS: 0 = no disease activity to 100 = maximum disease activity] and the ESR for a total possible score of 0 to 10. Scores < 2.6 indicate best disease control and scores ≥ 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6. An improvement of >1.2 was considered to be clinically significant improvement. | ITT population; Only participants with DAS28 values at both Baseline and Week 24 were included in the analysis. | Posted | Number | percentage of participants | Baseline and Week 24 |
|
|
|
| Secondary | Change in Bone Density (in Participants Untreated With Bisphosphonates) | Bone mineral density test was performed using x-ray radiation and the values of bone density were provided directly by the apparatus as grams per square centimeter (g/cm^2) . T-score is the number of standard deviations above or below the mean for a healthy 30 year old adult of the same sex and ethnicity as the participant. A T-score with above -1 is normal bone density level. A T-score between -1 and -2.5 means that the bone density is below normal and it might be a sign of an osteopenia and may also lead into osteoporosis. A T-score below -2.5 indicates osteoporosis. | ITT population; only participants with an assessment at both screening and Week 84 were included in the analysis. | Posted | Number | t-score | Screening and Week 84 |
|
|
|
| 6 |
| 18 |
| 9 |
| 18 |
| Persistent thrombopenia | Blood and lymphatic system disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Rectal bleeding | Gastrointestinal disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Ventricular Extra systolebigeminy | Cardiac disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Severe infusion reaction | Injury, poisoning and procedural complications | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Hyperglycemia | Endocrine disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Multi-sensitive Streptococcus Cystitis | Infections and infestations | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Hypertension | Blood and lymphatic system disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Keratitis Secca | Skin and subcutaneous tissue disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Red Throat | General disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Somnolence | General disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Influenza | Infections and infestations | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Muscular Pain | Musculoskeletal and connective tissue disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Nocturnal Sweating | General disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Headache | General disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Dyspnea Stage 2 | Respiratory, thoracic and mediastinal disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Productive Cough-Yellow Expectorations | Respiratory, thoracic and mediastinal disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Pneumopathy Infection | Infections and infestations | CTCAE (Unspecified) | Non-systematic Assessment |
|
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 |
| D011239 | Prednisolone |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |