A Study of Combination Treatment With MabThera (Rituximab) and RoActemra (Tocilizumab) Versus RoActemra in Patients With Rheumatoid Arthritis With an Incomplete Response to Methotrexate
Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Terminated
CT.gov ID
NCT00845832
Collaborator
(none)
24
24
2
48
1
0
Study Details
Study Description
Brief Summary
This 2 part study will investigate the safety, tolerability and efficacy of MabT hera in combination with RoActemra in patients with active rheumatoid arthritis despite a stable dose of methotrexate. In Part 1 of the study, patients will be randomized to receive either MabThera 0.5g iv or placebo on days 1 and 15, follo wed by RoActemra at one of the ascending doses between 2mg/kg and 8mg/kg at week s 4, 8 and 12 (MabThera arm) or 8mg/kg (placebo arm). In Part 2, additional pati ents will be randomized to one of 2 groups to receive MabThera 0.5g on days 1 an d 15 followed by the selected dose (from Part 1)of RoActemra at weeks 4, 8 and 1 2, or placebo on days 1 and 15 followed by RoActemra 8mg/kg at weeks 4,8 and 12.
All patients will then be eligible to receive extension treatment withRoActemra every 4 weeks. The anticipated time on study treatment is 12 months, and the tar get sample size is <100 individuals.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
24 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Active Controlled, Double-blind, Study to Compare the Safety and Reduction in Disease Activity With the Combination of Rituximab (MabThera®)and Tocilizumab (RoActemra®) Versus Tocilizumab in Patients With Active Rheumatoid Arthritis With an Incomplete Response to Methotrexate
Study Start Date
:
Mar 1, 2009
Actual Primary Completion Date
:
Mar 1, 2013
Actual Study Completion Date
:
Mar 1, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1
|
Drug: rituximab [MabThera/Rituxan]
0.5g iv on days 1 and 15 (Parts 1 and 2)
Drug: tocilizumab [RoActemra/Actemra]
2mg/kg-8mg/kg iv in Part 1 and selected dose in Part 2, on weeks 4, 8 and 12---Arm 1\n8mg/kg iv on weeks 4,8 and 12 (Parts 1 and 2)--- Arm 2
|
| Active Comparator: 2
|
Drug: Placebo
iv on days 1 and 15 (Parts 1 and 2)
Drug: tocilizumab [RoActemra/Actemra]
2mg/kg-8mg/kg iv in Part 1 and selected dose in Part 2, on weeks 4, 8 and 12---Arm 1\n8mg/kg iv on weeks 4,8 and 12 (Parts 1 and 2)--- Arm 2
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Achieving Low Disease Activity (LDA) at Week 16 Assessed Using Disease Activity Score Based on 28 Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR) [Week 16]
The Disease Activity Score based on 28 joint count (DAS28) and Erythrocyte Sedimentation Rate (ESR), is a measure of the participant's disease activity. It is based on the Tender Joint Count (TJC [28 joints]), Swollen Joint Count (SJC [28 joints]), participant's global assessment of disease activity (PtGA) Visual Analog Scale (VAS) in millimeters (mm), and ESR in millimeters per hour (mm/hour). DAS28-ESR scores range from 0 - 10. Definition of LDA was based on DAS28-ESR scores. To achieve LDA the DAS28-ESR had to be (less than or equal to) ≤ 3.2. DAS28-ESR equals (=) (0.56 times (*) (square root)√ TJC plus (+) (0.28 * √ SJC + (0.70 * ln(ESR))+(0.014 * (Global Health) GH) Where: TJC = based on 28 joints SJC = based on 28 joints ESR = erythrocyte sedimentation rate in mm/hour GH = participant's global assessment of disease activity ln = natural log
Secondary Outcome Measures
- Percentage of Participants Achieving Remission at Week 16 Assessed Using DAS28-ESR [Week 16]
The DAS28-ESR score is a measure of the participant's disease activity. It is based on the TJC (28 joints), SJC (28 joints), participant's global assessment of disease activity (mm), and ESR (mm/hour). DAS28-ESR is expressed on a unit on a scale with the minimum score=0 (best) to maximum score=10 (worst). Remission was defined as DAS28-ESR less than (<) 2.6
- Percentage of Participants by European League Against Rheumatism (EULAR) Response Category at Week 16 [Week 16]
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 (greater than) >1.2 with DAS28 ≤3.2; moderate responders: change from baseline >1.2 with DAS28 >3.2 to ≤5.1 or DAS28-ESR >5.1 or change from baseline >0.6 to ≤1.2 with DAS28 ≤5.1; nonresponders: change from baseline ≤0.6 or change from baseline >0.6 and ≤1.2 with DAS28 >5.1.
- Change From Baseline in DAS28-ESR [Weeks 4, 8, 12, 16, 20, 24, 32, 40 and 48]
The DAS28-ESR score is a measure of the participant's disease activity. It is based on the TJC (28 joints), SJC (28 joints), participant's global assessment of disease activity (mm), and ESR (mm/hour). DAS28-ESR is expressed as a score on a scale with the minimum score=0 (best) to maximum score=10 (worst). DAS28-ESR scores were calculated as follows: DAS28-ESR = (0.56 * √TJC)+(0.28 * √SJC)+(0.70 * ln(ESR))+(0.014 * GH). No imputation used for tender and swollen joint counts, ESR, and patient's global assessment of disease activity VAS.
- Clinical Disease Activity Index Scores [Baseline and Weeks 4, 8, 12, 16, 20, 24, 32, 40 and 48]
The Clinical Disease Activity Index (CDAI) score was calculated according to the following formula: CDAI = SJC + TJC + GH/10 + EGA/10 Where: SJC = swollen joint count based on 28 joints; TJC = tender joint count based on 28 joints; GH = Participant's global assessment of disease activity; EGA = evaluator's (physician's) global assessment of disease activity. CDAI scores range from 0-76 and the following cut-off points for different disease activity states have been used: high disease activity >22; moderate disease activity >10 and ≤22; LDA >2.8 and ≤10; and remission ≤ 2.8. No imputation used for TJC, SJC, Patient's Global Assessment of Disease Activity VAS and Physicians global assessment of disease activity VAS.
- Simplified Disease Activity Index (SDAI) Scores [Baseline and Weeks 4, 8, 12, 16, 20, 24, 32, 40, and 48]
The SDAI is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), Participant and Physician assessed global disease activity (assessed on 0-100 mm VAS; higher scores = greater affection due to disease activity), and ESR (mm/hour). SDAI total score ranged from 0 to 86. Higher scores indicated greater disease activity.
- Change From Baseline to Week 48 in SJC and TJC [Baseline and Week 48]
An assessment of 28 joints for swelling and tenderness will be made. Joints will be assessed and classified as swollen (1)/not swollen (0) and tender(1)/not tender (0) by pressure and joint manipulation on physical examination. Joint prosthesis, arthrodesis or fused joints were not taken into consideration for swelling or tenderness. The 28 joints assessed comprise shoulders (2 joints), elbows (2 joints), wrists (2 joints), metacarpophalangeal joints on digits 1-5 (10 joints), interphalangeal on digit 1 (2 joints), proximal interphalangeal joints on digits 2-5 (8 joints), and knees (2 joints).
- Change From Baseline to Week 48 in Health Assessment Questionnaire (HAQ) [Baseline and Week 48]
The Stanford Health Assessment Questionnaire disability index specific for rheumatoid arthritis was completed by the participants for efficacy assessments.
- Change From Baseline to Week 48 in C-Reactive Protein (CRP) [Baseline and Week 48]
CRP is an acute phase reactant and is a measure of inflammation.
- Change From Baseline to Week 48 in ESR [Baseline and Week 48]
ESR is an acute phase reactant and is a measure of inflammation.
- Change From Baseline to Week 48 in Physician's Global Assessment of Disease Activity [Baseline and Week 48]
Physician Global Assessment of Disease Activity was measured on a 0 to 100 mm VAS, with 0 mm = no disease activity and 100 mm= maximum disease activity. The physician marked the line according to their assessment and the distance from the left edge was measured.
- Change From Baseline to Week 48 in Participant's Global Assessment of Disease Activity [Baseline and Week 48]
Participant's Global Assessment of Disease Activity was measured on a 0 to 100 mm VAS, with 0 mm = no disease activity and 100 mm = maximum disease activity. The participant marked the line according to their assessment and the distance from the left edge was measured.
- Change From Baseline to Week 48 in Participant's Assessment of Pain [Baseline and Week 48]
Participant's Global Assessment of Disease Activity was measured on a 0 to 100 mm VAS, with 0 mm = no pain and 100 mm = maximum pain. The participant marked the line according to their assessment and the distance from the left edge was measured.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
adult patients, 18-65 years of age;
-
rheumatoid arthritis, functional status I-III;
-
SJC>=4 (28 joint count) and TJC>=4 (28 joint count) at screening and baseline;
-
RF and/or anti-CCP positive;
-
may have failed up to 1 approved anti-TNF agent (infliximab, etanercept or adalimumab);
-
inadequate response to methotrexate, at a dose of 7.5-25mg weekly for at least 12 weeks, at a stable dose for past 4 weeks.
Exclusion Criteria:
-
rheumatic autoimmune disease other than rheumatoid arthritis, or significant systemic involvement secondary to rheumatoid arthritis;
-
history of, or current, inflammatory joint disease other than rheumatoid arthritis;
-
diagnosis of juvenile idiopathic arthritis and/or rheumatoid arthritis before age 16;
-
significant cardiac or pulmonary disease;
-
previous treatment with any biologic agent for rheumatoid arthritis (other than infliximab, etanercept or adalimumab).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Le Kremlin Bicetre | France | 94275 | ||
| 2 | Montpellier | France | 34295 | ||
| 3 | Paris | France | 75679 | ||
| 4 | Strasbourg | France | 67098 | ||
| 5 | Berlin | Germany | 10117 | ||
| 6 | Berlin | Germany | 14059 | ||
| 7 | Heidelberg | Germany | 69120 | ||
| 8 | Köln | Germany | 50924 | ||
| 9 | Wuerzburg | Germany | 97080 | ||
| 10 | Athens | Greece | 15121 | ||
| 11 | Thessaloniki | Greece | 54636 | ||
| 12 | Amsterdam | Netherlands | 1105 AZ | ||
| 13 | Leiden | Netherlands | 2333 ZA | ||
| 14 | Bytom | Poland | 41-902 | ||
| 15 | Lublin | Poland | 20-607 | ||
| 16 | Poznan | Poland | 60-218 | ||
| 17 | Santander | Cantabria | Spain | 39008 | |
| 18 | Santiago de Compostela | La Coruña | Spain | 15706 | |
| 19 | Madrid | Spain | 28007 | ||
| 20 | Sevilla | Spain | 41009 | ||
| 21 | Bern | Switzerland | 3010 | ||
| 22 | Lausanne | Switzerland | 1011 | ||
| 23 | Newcastle Upon Tyne | United Kingdom | NE1 4LP | ||
| 24 | Southampton | United Kingdom | SO16 6YD |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00845832
Other Study ID Numbers:
- WX21956
- 2008-005525-11
First Posted:
Feb 18, 2009
Last Update Posted:
Dec 24, 2014
Last Verified:
Dec 1, 2014
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Placebo + Tocilizumab (TCZ) 8 Milligrams Per Kilogram (mg/kg) | Rituximab (0.5 Grams [g]) + TCZ (2 mg/kg) | Rituximab (0.5 g) + TCZ (4 mg/kg) |
|---|---|---|---|
| Arm/Group Description | Participants received placebo intravenously (iv) on Days 1 and 15 followed by TCZ 8 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 2 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 4 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. |
| Period Title: Treatment Period | |||
| STARTED | 4 | 10 | 10 |
| COMPLETED | 3 | 7 | 10 |
| NOT COMPLETED | 1 | 3 | 0 |
| Period Title: Treatment Period | |||
| STARTED | 3 | 9 | 12 |
| COMPLETED | 2 | 9 | 12 |
| NOT COMPLETED | 1 | 0 | 0 |
| Period Title: Treatment Period | |||
| STARTED | 2 | 5 | 7 |
| COMPLETED | 2 | 5 | 0 |
| NOT COMPLETED | 0 | 0 | 7 |
Baseline Characteristics
| Arm/Group Title | Placebo + TCZ (8 mg/kg) | Rituximab (0.5 g) + TCZ (2 mg/kg) | Rituximab (0.5 g) + TCZ (4 mg/kg) | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants received placebo iv on Days 1 and 15 followed by TCZ 8 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 2 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 4 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Total of all reporting groups |
| Overall Participants | 3 | 9 | 12 | 24 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
41.3
(11.02)
|
48.2
(10.50)
|
50.0
(6.97)
|
48.3
(8.94)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
3
100%
|
7
77.8%
|
10
83.3%
|
20
83.3%
|
| Male |
0
0%
|
2
22.2%
|
2
16.7%
|
4
16.7%
|
Outcome Measures
| Title | Percentage of Participants Achieving Low Disease Activity (LDA) at Week 16 Assessed Using Disease Activity Score Based on 28 Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR) |
|---|---|
| Description | The Disease Activity Score based on 28 joint count (DAS28) and Erythrocyte Sedimentation Rate (ESR), is a measure of the participant's disease activity. It is based on the Tender Joint Count (TJC [28 joints]), Swollen Joint Count (SJC [28 joints]), participant's global assessment of disease activity (PtGA) Visual Analog Scale (VAS) in millimeters (mm), and ESR in millimeters per hour (mm/hour). DAS28-ESR scores range from 0 - 10. Definition of LDA was based on DAS28-ESR scores. To achieve LDA the DAS28-ESR had to be (less than or equal to) ≤ 3.2. DAS28-ESR equals (=) (0.56 times (*) (square root)√ TJC plus (+) (0.28 * √ SJC + (0.70 * ln(ESR))+(0.014 * (Global Health) GH) Where: TJC = based on 28 joints SJC = based on 28 joints ESR = erythrocyte sedimentation rate in mm/hour GH = participant's global assessment of disease activity ln = natural log |
| Time Frame | Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) Population: all randomized participants who received any part of an infusion of study medication. Last observation carried forward (LOCF) used for TJC and SJC, ESR and PtGA. If DAS28-ESR value was missing LDA was missing. |
| Arm/Group Title | Placebo + TCZ (8 mg/kg) | Rituximab (0.5 g) + TCZ (2 mg/kg) | Rituximab (0.5 g) + TCZ (4 mg/kg) |
|---|---|---|---|
| Arm/Group Description | Participants received placebo iv on Days 1 and 15 followed by TCZ 8 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 2 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 4 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. |
| Measure Participants | 4 | 9 | 10 |
| Number [percentage of participants] |
50.0
1666.7%
|
11.1
123.3%
|
20.0
166.7%
|
| Title | Percentage of Participants Achieving Remission at Week 16 Assessed Using DAS28-ESR |
|---|---|
| Description | The DAS28-ESR score is a measure of the participant's disease activity. It is based on the TJC (28 joints), SJC (28 joints), participant's global assessment of disease activity (mm), and ESR (mm/hour). DAS28-ESR is expressed on a unit on a scale with the minimum score=0 (best) to maximum score=10 (worst). Remission was defined as DAS28-ESR less than (<) 2.6 |
| Time Frame | Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population; LOCF used for TJC, ESR, and PtGA. If the DAS28-ESR value was missing then remission or LDA was missing. |
| Arm/Group Title | Placebo + TCZ (8 mg/kg) | Rituximab (0.5 g) + TCZ (2 mg/kg) | Rituximab (0.5 g) + TCZ (4 mg/kg) |
|---|---|---|---|
| Arm/Group Description | Participants received placebo iv on Days 1 and 15 followed by TCZ 8 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 2 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 4 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. |
| Measure Participants | 4 | 9 | 10 |
| Number [percentage of participants] |
0.0
0%
|
0.0
0%
|
10.0
83.3%
|
| Title | Percentage of Participants by European League Against Rheumatism (EULAR) Response Category at Week 16 |
|---|---|
| Description | 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 (greater than) >1.2 with DAS28 ≤3.2; moderate responders: change from baseline >1.2 with DAS28 >3.2 to ≤5.1 or DAS28-ESR >5.1 or change from baseline >0.6 to ≤1.2 with DAS28 ≤5.1; nonresponders: change from baseline ≤0.6 or change from baseline >0.6 and ≤1.2 with DAS28 >5.1. |
| Time Frame | Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population; No imputation used for TJC, SJC, ESR, and PtGA. EULAR response was set to missing when the DAS28 score was missing. |
| Arm/Group Title | Placebo + TCZ (8 mg/kg) | Rituximab (0.5 g) + TCZ (2 mg/kg) | Rituximab (0.5 g) + TCZ (4 mg/kg) |
|---|---|---|---|
| Arm/Group Description | Participants received placebo iv on Days 1 and 15 followed by TCZ 8 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 2 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 4 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. |
| Measure Participants | 4 | 9 | 9 |
| No Response |
0.0
0%
|
22.2
246.7%
|
11.1
92.5%
|
| Moderate Response |
50.0
1666.7%
|
66.7
741.1%
|
66.7
555.8%
|
| Good Response |
50.0
1666.7%
|
11.1
123.3%
|
22.2
185%
|
| Title | Change From Baseline in DAS28-ESR |
|---|---|
| Description | The DAS28-ESR score is a measure of the participant's disease activity. It is based on the TJC (28 joints), SJC (28 joints), participant's global assessment of disease activity (mm), and ESR (mm/hour). DAS28-ESR is expressed as a score on a scale with the minimum score=0 (best) to maximum score=10 (worst). DAS28-ESR scores were calculated as follows: DAS28-ESR = (0.56 * √TJC)+(0.28 * √SJC)+(0.70 * ln(ESR))+(0.014 * GH). No imputation used for tender and swollen joint counts, ESR, and patient's global assessment of disease activity VAS. |
| Time Frame | Weeks 4, 8, 12, 16, 20, 24, 32, 40 and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population; number (n) = number of participants analyzed at the specified visit. |
| Arm/Group Title | Placebo + TCZ (8 mg/kg) | Rituximab (0.5 g) + TCZ (2 mg/kg) | Rituximab (0.5 g) + TCZ (4 mg/kg) |
|---|---|---|---|
| Arm/Group Description | Participants received placebo iv on Days 1 and 15 followed by TCZ 8 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 2 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 4 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. |
| Measure Participants | 4 | 10 | 10 |
| Week 4 (n=4,9,10) |
-1.9
(1.73)
|
-0.7
(1.44)
|
-1.0
(0.72)
|
| Week 8 (n=4,10,10) |
-2.7
(0.55)
|
-0.5
(1.33)
|
-1.9
(1.31)
|
| Week 12 (n=4,10,9) |
-2.7
(0.57)
|
-1.2
(1.60)
|
-2.3
(1.36)
|
| Week 16 (n=4,9,9) |
-3.0
(0.80)
|
-1.8
(1.44)
|
-2.3
(1.25)
|
| Week 20 (n=4,9,9) |
-3.6
(0.70)
|
-2.2
(1.16)
|
-2.7
(1.45)
|
| Week 24 (n=4,9,8) |
-3.5
(1.28)
|
-2.2
(1.14)
|
-2.9
(1.34)
|
| Week 32 (n=4,9,8) |
-2.6
(1.62)
|
-3.1
(1.92)
|
-3.3
(1.83)
|
| Week 40 (n=3,8,8) |
-2.6
(1.24)
|
-2.2
(1.63)
|
-2.7
(1.02)
|
| Week 48 (n=4,8,7) |
-3.3
(1.84)
|
-2.9
(1.50)
|
-3.0
(1.24)
|
| Title | Clinical Disease Activity Index Scores |
|---|---|
| Description | The Clinical Disease Activity Index (CDAI) score was calculated according to the following formula: CDAI = SJC + TJC + GH/10 + EGA/10 Where: SJC = swollen joint count based on 28 joints; TJC = tender joint count based on 28 joints; GH = Participant's global assessment of disease activity; EGA = evaluator's (physician's) global assessment of disease activity. CDAI scores range from 0-76 and the following cut-off points for different disease activity states have been used: high disease activity >22; moderate disease activity >10 and ≤22; LDA >2.8 and ≤10; and remission ≤ 2.8. No imputation used for TJC, SJC, Patient's Global Assessment of Disease Activity VAS and Physicians global assessment of disease activity VAS. |
| Time Frame | Baseline and Weeks 4, 8, 12, 16, 20, 24, 32, 40 and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population; n=number of participants analyzed for the given parameter at the specified timepoint. |
| Arm/Group Title | Placebo + TCZ (8 mg/kg) | Rituximab (0.5 g) + TCZ (2 mg/kg) | Rituximab (0.5 g) + TCZ (4 mg/kg) |
|---|---|---|---|
| Arm/Group Description | Participants received placebo iv on Days 1 and 15 followed by TCZ 8 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 2 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 4 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. |
| Measure Participants | 4 | 10 | 10 |
| Baseline (n=4, 10, 10) |
37.7
(4.59)
|
36.4
(9.16)
|
33.0
(7.69)
|
| Week 4 (n=4, 8, 10) |
21.2
(14.19)
|
23.4
(12.38)
|
20.0
(6.97)
|
| Week 8 (n=4,10,10) |
14.6
(4.38)
|
29.4
(14.91)
|
15.5
(9.96)
|
| Week 12 (n=4,10, 9) |
16.3
(10.52)
|
23.2
(12.47)
|
13.4
(8.40)
|
| Week 16 (n=4,10, 9) |
9.5
(5.70)
|
19.5
(15.42)
|
12.7
(8.32)
|
| Week 20 (n=4, 8, 9) |
10.8
(4.46)
|
15.4
(7.76)
|
11.6
(6.64)
|
| Week 24 (n=4, 9, 8) |
9.2
(6.71)
|
12.6
(3.98)
|
10.9
(5.47)
|
| Week 32 (n=4, 9, 8) |
15.2
(10.42)
|
11.5
(13.14)
|
9.3
(9.42)
|
| Week 40 (n=3, 8, 8) |
20.3
(8.35)
|
17.9
(16.40)
|
11.8
(5.31)
|
| Week 48 (n=4, 7, 8) |
11.6
(10.11)
|
12.8
(12.15)
|
7.1
(6.41)
|
| Title | Simplified Disease Activity Index (SDAI) Scores |
|---|---|
| Description | The SDAI is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), Participant and Physician assessed global disease activity (assessed on 0-100 mm VAS; higher scores = greater affection due to disease activity), and ESR (mm/hour). SDAI total score ranged from 0 to 86. Higher scores indicated greater disease activity. |
| Time Frame | Baseline and Weeks 4, 8, 12, 16, 20, 24, 32, 40, and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data were not collected because the study was terminated early. |
| Arm/Group Title | Placebo + TCZ (8 mg/kg) | Rituximab (0.5 g) + TCZ (2 mg/kg) | Rituximab (0.5 g) + TCZ (4 mg/kg) |
|---|---|---|---|
| Arm/Group Description | Participants received placebo iv on Days 1 and 15 followed by TCZ 8 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 2 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 4 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. |
| Measure Participants | 0 | 0 | 0 |
| Title | Change From Baseline to Week 48 in SJC and TJC |
|---|---|
| Description | An assessment of 28 joints for swelling and tenderness will be made. Joints will be assessed and classified as swollen (1)/not swollen (0) and tender(1)/not tender (0) by pressure and joint manipulation on physical examination. Joint prosthesis, arthrodesis or fused joints were not taken into consideration for swelling or tenderness. The 28 joints assessed comprise shoulders (2 joints), elbows (2 joints), wrists (2 joints), metacarpophalangeal joints on digits 1-5 (10 joints), interphalangeal on digit 1 (2 joints), proximal interphalangeal joints on digits 2-5 (8 joints), and knees (2 joints). |
| Time Frame | Baseline and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data were not collected because the study was terminated early. |
| Arm/Group Title | Placebo + TCZ (8 mg/kg) | Rituximab (0.5 g) + TCZ (2 mg/kg) | Rituximab (0.5 g) + TCZ (4 mg/kg) |
|---|---|---|---|
| Arm/Group Description | Participants received placebo iv on Days 1 and 15 followed by TCZ 8 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 2 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 4 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. |
| Measure Participants | 0 | 0 | 0 |
| Title | Change From Baseline to Week 48 in Health Assessment Questionnaire (HAQ) |
|---|---|
| Description | The Stanford Health Assessment Questionnaire disability index specific for rheumatoid arthritis was completed by the participants for efficacy assessments. |
| Time Frame | Baseline and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data were not collected because the study was terminated early. |
| Arm/Group Title | Placebo + TCZ (8 mg/kg) | Rituximab (0.5 g) + TCZ (2 mg/kg) | Rituximab (0.5 g) + TCZ (4 mg/kg) |
|---|---|---|---|
| Arm/Group Description | Participants received placebo iv on Days 1 and 15 followed by TCZ 8 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 2 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 4 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. |
| Measure Participants | 0 | 0 | 0 |
| Title | Change From Baseline to Week 48 in C-Reactive Protein (CRP) |
|---|---|
| Description | CRP is an acute phase reactant and is a measure of inflammation. |
| Time Frame | Baseline and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data were not collected because the study was terminated early. |
| Arm/Group Title | Placebo + TCZ (8 mg/kg) | Rituximab (0.5 g) + TCZ (2 mg/kg) | Rituximab (0.5 g) + TCZ (4 mg/kg) |
|---|---|---|---|
| Arm/Group Description | Participants received placebo iv on Days 1 and 15 followed by TCZ 8 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 2 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 4 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. |
| Measure Participants | 0 | 0 | 0 |
| Title | Change From Baseline to Week 48 in ESR |
|---|---|
| Description | ESR is an acute phase reactant and is a measure of inflammation. |
| Time Frame | Baseline and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data were not collected because the study was terminated early. |
| Arm/Group Title | Placebo + TCZ (8 mg/kg) | Rituximab (0.5 g) + TCZ (2 mg/kg) | Rituximab (0.5 g) + TCZ (4 mg/kg) |
|---|---|---|---|
| Arm/Group Description | Participants received placebo iv on Days 1 and 15 followed by TCZ 8 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 2 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 4 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. |
| Measure Participants | 0 | 0 | 0 |
| Title | Change From Baseline to Week 48 in Physician's Global Assessment of Disease Activity |
|---|---|
| Description | Physician Global Assessment of Disease Activity was measured on a 0 to 100 mm VAS, with 0 mm = no disease activity and 100 mm= maximum disease activity. The physician marked the line according to their assessment and the distance from the left edge was measured. |
| Time Frame | Baseline and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data were not collected because the study was terminated early. |
| Arm/Group Title | Placebo + TCZ (8 mg/kg) | Rituximab (0.5 g) + TCZ (2 mg/kg) | Rituximab (0.5 g) + TCZ (4 mg/kg) |
|---|---|---|---|
| Arm/Group Description | Participants received placebo iv on Days 1 and 15 followed by TCZ 8 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 2 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 4 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. |
| Measure Participants | 0 | 0 | 0 |
| Title | Change From Baseline to Week 48 in Participant's Global Assessment of Disease Activity |
|---|---|
| Description | Participant's Global Assessment of Disease Activity was measured on a 0 to 100 mm VAS, with 0 mm = no disease activity and 100 mm = maximum disease activity. The participant marked the line according to their assessment and the distance from the left edge was measured. |
| Time Frame | Baseline and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data were not collected because the study was terminated early. |
| Arm/Group Title | Placebo + TCZ (8 mg/kg) | Rituximab (0.5 g) + TCZ (2 mg/kg) | Rituximab (0.5 g) + TCZ (4 mg/kg) |
|---|---|---|---|
| Arm/Group Description | Participants received placebo iv on Days 1 and 15 followed by TCZ 8 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 2 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 4 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. |
| Measure Participants | 0 | 0 | 0 |
| Title | Change From Baseline to Week 48 in Participant's Assessment of Pain |
|---|---|
| Description | Participant's Global Assessment of Disease Activity was measured on a 0 to 100 mm VAS, with 0 mm = no pain and 100 mm = maximum pain. The participant marked the line according to their assessment and the distance from the left edge was measured. |
| Time Frame | Baseline and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data were not collected because the study was terminated early. |
| Arm/Group Title | Placebo + TCZ (8 mg/kg) | Rituximab (0.5 g) + TCZ (2 mg/kg) | Rituximab (0.5 g) + TCZ (4 mg/kg) |
|---|---|---|---|
| Arm/Group Description | Participants received placebo iv on Days 1 and 15 followed by TCZ 8 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 2 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 4 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. |
| Measure Participants | 0 | 0 | 0 |
Adverse Events
| Time Frame | Adverse Events were recorded throughout the study from the date of first study drug administration until 48 weeks of treatment period and for those in the Safety follow up population until the end of follow up period. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Participants who received the incorrect therapy from that intended were summarized in the group according to the therapy actually received for the majority of the time through Week 48. 1 participant each from Placebo + TCZ (8 mg/kg) and Rituximab (0.5 g) + TCZ (2 mg/kg) groups was included in Rituximab (0.5 g) + TCZ (4 mg/kg) group. | |||||
| Arm/Group Title | Placebo + TCZ (8 mg/kg) | Rituximab (0.5 g) + TCZ (2 mg/kg) | Rituximab (0.5 g) + TCZ (4 mg/kg) | |||
| Arm/Group Description | Participants received placebo iv on Days 1 and 15 followed by TCZ 8 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 2 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 4 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid. | |||
All Cause Mortality |
||||||
| Placebo + TCZ (8 mg/kg) | Rituximab (0.5 g) + TCZ (2 mg/kg) | Rituximab (0.5 g) + TCZ (4 mg/kg) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Placebo + TCZ (8 mg/kg) | Rituximab (0.5 g) + TCZ (2 mg/kg) | Rituximab (0.5 g) + TCZ (4 mg/kg) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/3 (33.3%) | 2/9 (22.2%) | 3/12 (25%) | |||
| Gastrointestinal disorders | ||||||
| Large intestinal ulcer haemorrhage | 0/3 (0%) | 0/9 (0%) | 1/12 (8.3%) | |||
| Umbilical hernia | 0/3 (0%) | 0/9 (0%) | 1/12 (8.3%) | |||
| General disorders | ||||||
| Chest pain | 0/3 (0%) | 0/9 (0%) | 1/12 (8.3%) | |||
| Infusion related reaction | 0/3 (0%) | 1/9 (11.1%) | 0/12 (0%) | |||
| Infections and infestations | ||||||
| Pneumonia | 0/3 (0%) | 1/9 (11.1%) | 0/12 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Rotator cuff syndrome | 1/3 (33.3%) | 0/9 (0%) | 0/12 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Pneumonitis | 0/3 (0%) | 1/9 (11.1%) | 0/12 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Placebo + TCZ (8 mg/kg) | Rituximab (0.5 g) + TCZ (2 mg/kg) | Rituximab (0.5 g) + TCZ (4 mg/kg) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 9/9 (100%) | 11/12 (91.7%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 0/3 (0%) | 2/9 (22.2%) | 0/12 (0%) | |||
| Neutropenia | 0/3 (0%) | 0/9 (0%) | 1/12 (8.3%) | |||
| Eye disorders | ||||||
| Corneal erosion | 0/3 (0%) | 1/9 (11.1%) | 0/12 (0%) | |||
| Glaucoma | 0/3 (0%) | 0/9 (0%) | 1/12 (8.3%) | |||
| Presbyopia | 0/3 (0%) | 1/9 (11.1%) | 0/12 (0%) | |||
| Cataract | 0/3 (0%) | 1/9 (11.1%) | 0/12 (0%) | |||
| Gastrointestinal disorders | ||||||
| Dyspepsia | 0/3 (0%) | 3/9 (33.3%) | 0/12 (0%) | |||
| Nausea | 2/3 (66.7%) | 0/9 (0%) | 1/12 (8.3%) | |||
| Gastritis | 0/3 (0%) | 2/9 (22.2%) | 0/12 (0%) | |||
| Abdominal discomfort | 0/3 (0%) | 0/9 (0%) | 1/12 (8.3%) | |||
| Abdominal pain upper | 0/3 (0%) | 0/9 (0%) | 1/12 (8.3%) | |||
| Constipation | 0/3 (0%) | 1/9 (11.1%) | 0/12 (0%) | |||
| Hiatus hernia | 0/3 (0%) | 1/9 (11.1%) | 0/12 (0%) | |||
| Mouth ulceration | 0/3 (0%) | 1/9 (11.1%) | 0/12 (0%) | |||
| General disorders | ||||||
| Infusion related reaction | 0/3 (0%) | 3/9 (33.3%) | 1/12 (8.3%) | |||
| Asthenia | 0/3 (0%) | 1/9 (11.1%) | 2/12 (16.7%) | |||
| Oedema peripheral | 2/3 (66.7%) | 1/9 (11.1%) | 0/12 (0%) | |||
| Fatigue | 0/3 (0%) | 0/9 (0%) | 1/12 (8.3%) | |||
| Rash | 0/3 (0%) | 1/9 (11.1%) | 0/12 (0%) | |||
| Cervix Disorder | 0/3 (0%) | 1/9 (11.1%) | 0/12 (0%) | |||
| Tooth Ache | 0/3 (0%) | 1/9 (11.1%) | 0/12 (0%) | |||
| Immune system disorders | ||||||
| Hypersensitivity | 1/3 (33.3%) | 1/9 (11.1%) | 0/12 (0%) | |||
| Seasonal Allergy | 1/3 (33.3%) | 1/9 (11.1%) | 0/12 (0%) | |||
| Asthma | 0/3 (0%) | 1/9 (11.1%) | 0/12 (0%) | |||
| Infections and infestations | ||||||
| Nasopharyngitis | 1/3 (33.3%) | 0/9 (0%) | 2/12 (16.7%) | |||
| Bronchitis | 0/3 (0%) | 1/9 (11.1%) | 2/12 (16.7%) | |||
| Oral herpes | 0/3 (0%) | 1/9 (11.1%) | 1/12 (8.3%) | |||
| Acute tonsillitis | 1/3 (33.3%) | 0/9 (0%) | 0/12 (0%) | |||
| Dermatitis infected | 0/3 (0%) | 1/9 (11.1%) | 0/12 (0%) | |||
| Gastroenteritis | 0/3 (0%) | 0/9 (0%) | 1/12 (8.3%) | |||
| Infected bites | 0/3 (0%) | 1/9 (11.1%) | 0/12 (0%) | |||
| Influenza | 0/3 (0%) | 1/9 (11.1%) | 0/12 (0%) | |||
| Rhinitis | 0/3 (0%) | 0/9 (0%) | 1/12 (8.3%) | |||
| Tooth infection | 0/3 (0%) | 0/9 (0%) | 1/12 (8.3%) | |||
| Urinary tract infection | 0/3 (0%) | 0/9 (0%) | 1/12 (8.3%) | |||
| Herpes Zoster | 0/3 (0%) | 1/9 (11.1%) | 0/12 (0%) | |||
| Pyrexia | 0/3 (0%) | 0/9 (0%) | 1/12 (8.3%) | |||
| Sinusitis | 0/3 (0%) | 0/9 (0%) | 1/12 (8.3%) | |||
| Wound Infection | 0/3 (0%) | 0/9 (0%) | 1/12 (8.3%) | |||
| Injury, poisoning and procedural complications | ||||||
| Upper respiratory tract infection | 0/3 (0%) | 3/9 (33.3%) | 3/12 (25%) | |||
| Thermal burn | 0/3 (0%) | 1/9 (11.1%) | 0/12 (0%) | |||
| Investigations | ||||||
| Blood bilirubin increased | 0/3 (0%) | 0/9 (0%) | 1/12 (8.3%) | |||
| Transaminases increased | 0/3 (0%) | 0/9 (0%) | 1/12 (8.3%) | |||
| Metabolism and nutrition disorders | ||||||
| Hypoglycaemia | 1/3 (33.3%) | 0/9 (0%) | 0/12 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 1/3 (33.3%) | 1/9 (11.1%) | 1/12 (8.3%) | |||
| Ligamentitis | 0/3 (0%) | 0/9 (0%) | 1/12 (8.3%) | |||
| Tenosynovitis stenosans | 0/3 (0%) | 1/9 (11.1%) | 0/12 (0%) | |||
| Myalgia | 0/3 (0%) | 1/9 (11.1%) | 0/12 (0%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Aphthous stomatitis | 0/3 (0%) | 1/9 (11.1%) | 0/12 (0%) | |||
| Nervous system disorders | ||||||
| Dizziness | 1/3 (33.3%) | 0/9 (0%) | 0/12 (0%) | |||
| Essential tremor | 0/3 (0%) | 1/9 (11.1%) | 0/12 (0%) | |||
| Occipital neuralgia | 0/3 (0%) | 1/9 (11.1%) | 0/12 (0%) | |||
| Occipital Neuralgia (left) | 0/3 (0%) | 3/9 (33.3%) | 0/12 (0%) | |||
| Occipital Neuralgia (right) | 0/3 (0%) | 1/9 (11.1%) | 0/12 (0%) | |||
| Psychiatric disorders | ||||||
| Anxiety Disorder | 0/3 (0%) | 1/9 (11.1%) | 0/12 (0%) | |||
| Reproductive system and breast disorders | ||||||
| Genital ulceration | 0/3 (0%) | 1/9 (11.1%) | 0/12 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Allergic bronchitis | 1/3 (33.3%) | 0/9 (0%) | 0/12 (0%) | |||
| Oropharyngeal pain | 0/3 (0%) | 0/9 (0%) | 1/12 (8.3%) | |||
| Pneumonia | 0/3 (0%) | 1/9 (11.1%) | 0/12 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Alopecia | 0/3 (0%) | 0/9 (0%) | 1/12 (8.3%) | |||
| Intertrigo | 0/3 (0%) | 1/9 (11.1%) | 0/12 (0%) | |||
| Photosensitivity reaction | 1/3 (33.3%) | 0/9 (0%) | 0/12 (0%) | |||
| Rosacea | 0/3 (0%) | 1/9 (11.1%) | 0/12 (0%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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 after the first publication or presentation that involves the overall study. Sponsor may request that confidential information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
| Name/Title | Medical Communications |
|---|---|
| Organization | Hoffmann- LaRoche |
| Phone | 1-800-821-8590 |
| genentech@druginfo.com |
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00845832
Other Study ID Numbers:
- WX21956
- 2008-005525-11
First Posted:
Feb 18, 2009
Last Update Posted:
Dec 24, 2014
Last Verified:
Dec 1, 2014