A Study of Rituximab (MabThera®/Rituxan®) in Patients With Rheumatoid Arthritis and Inadequate Response to Methotrexate (SCORE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00578305
First received: December 19, 2007
Last updated: March 26, 2015
Last verified: March 2015
Results First Received: February 19, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Rheumatoid Arthritis
Interventions: Biological: Rituximab
Drug: Placebo
Drug: Methylprednisolone
Drug: Methotrexate
Drug: Folic acid or folate

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
Rituximab 500 mg Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Rituximab 1000 mg Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Placebo Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.

Participant Flow for 3 periods

Period 1:   Double-blind Treatment Phase
    Rituximab 500 mg     Rituximab 1000 mg     Placebo  
STARTED     62     60     63  
Treated     62     60     63  
COMPLETED     59     56     49  
NOT COMPLETED     3     4     14  

Period 2:   Extension Phase
    Rituximab 500 mg     Rituximab 1000 mg     Placebo  
STARTED     53     50     43  
COMPLETED     49 [1]   49 [1]   40 [1]
NOT COMPLETED     4     1     3  
[1] Some participants completed the study in this period and did not enter the safety follow-up period.

Period 3:   Safety Follow-up Phase
    Rituximab 500 mg     Rituximab 1000 mg     Placebo  
STARTED     57 [1]   54 [1]   54 [1]
COMPLETED     11     9     8  
NOT COMPLETED     46     45     46  
[1] Some participants entered safety follow-up directly from the double-blind treatment period.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety population: All participants who received any part of an infusion of the study drug during the main study.

Reporting Groups
  Description
Rituximab 500 mg Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Rituximab 1000 mg Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Placebo Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
Total Total of all reporting groups

Baseline Measures
    Rituximab 500 mg     Rituximab 1000 mg     Placebo     Total  
Number of Participants  
[units: participants]
  62     60     63     185  
Age  
[units: years]
Mean ± Standard Deviation
  48.7  ± 11.10     50.7  ± 11.65     50.3  ± 11.94     49.9  ± 11.54  
Gender  
[units: participants]
       
Female     45     50     48     143  
Male     17     10     15     42  



  Outcome Measures
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1.  Primary:   Change in Magnetic Resonance Imaging (MRI) Erosion Score From Baseline to Week 24   [ Time Frame: Baseline to Week 24 ]

2.  Secondary:   Change in Magnetic Resonance Imaging (MRI) Erosion Score From Baseline to Weeks 12 and 52   [ Time Frame: Baseline to Week 52 ]

3.  Secondary:   Change in Magnetic Resonance Imaging (MRI) Synovitis Score From Baseline to Weeks 12, 24, and Week 52   [ Time Frame: Baseline to Week 52 ]

4.  Secondary:   Change in Magnetic Resonance Imaging (MRI) Osteitis Score From Baseline to Weeks 12, 24, and Week 52   [ Time Frame: Baseline to Week 52 ]

5.  Secondary:   Percentage of Participants With no Newly Eroded Joints at Weeks 24 and 52   [ Time Frame: Baseline to Week 52 ]

6.  Secondary:   Percentage of Participants With no Progression/no Worsening in Bone Erosion at Weeks 24 and 52   [ Time Frame: Baseline to Week 52 ]

7.  Secondary:   Percentage of Participants With Improvement in Synovitis at Weeks 24 and 52   [ Time Frame: Baseline to Week 52 ]

8.  Secondary:   Percentage of Participants With Improvement in Osteitis at Weeks 24 and 52   [ Time Frame: Baseline to Week 52 ]

9.  Secondary:   Change From Baseline in the Disease Activity Score 28 (DAS28) at Weeks 24 and 52   [ Time Frame: Baseline to Week 52 ]

10.  Secondary:   Percentage of Participants With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 24 and 52   [ Time Frame: Baseline to Week 52 ]

11.  Secondary:   Percentage of Participants With Low Disease Activity (Disease Activity Score 28 [DAS28] ≤ 3.2) at Weeks 24 and 52   [ Time Frame: Baseline to Week 52 ]

12.  Secondary:   Percentage of Participants in Remission Response (Disease Activity Score 28 [DAS28] < 2.6) at Weeks 24 and 52   [ Time Frame: Baseline to Week 52 ]

13.  Secondary:   Percentage of Participants With an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Weeks 24 and 52   [ Time Frame: Baseline to Week 52 ]

14.  Secondary:   Percentage of Participants Achieving a Major Clinical Response at Week 52   [ Time Frame: Baseline to Week 52 ]

15.  Secondary:   Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures   [ Time Frame: Baseline to Week 52 ]

16.  Secondary:   Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 24 and 52   [ Time Frame: Baseline to Week 52 ]

17.  Secondary:   Adverse Events (AEs), Laboratory Parameters, C-reactive Protein, ESR.   [ Time Frame: Throughout study ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
phone: 800 821-8590
e-mail: genentech@druginfo.com


No publications provided


Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00578305     History of Changes
Other Study ID Numbers: MA21056
Study First Received: December 19, 2007
Results First Received: February 19, 2015
Last Updated: March 26, 2015
Health Authority: Latvia: State Agency of Medicines