A Study of the Safety of Rituximab in Combination With Other Anti-Rheumatic Drugs in Subjects With Active Rheumatoid Arthritis (SUNDIAL)

This study has been completed.
Sponsor:
Collaborator:
Biogen Idec
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT00443651
First received: March 2, 2007
Last updated: May 20, 2013
Last verified: May 2013
Results First Received: April 18, 2012  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Rheumatoid Arthritis
Interventions: Drug: Rituximab
Drug: Anti-inflammatory drugs

  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
The study was conducted in 2 stages. Stage I: Patients with an inadequate response to non-biological disease-modifying antirheumatic drugs (DMARDS) were treated with rituximab 1000 mg. Stage II: Patients with an inadequate response to a biological DMARD were treated with rituximab 500 mg. Both groups continued to receive DMARDs.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
One Stage 1 patient was enrolled but did not receive treatment with rituximab, is not included in the Participant Flow data, and was not included in any of the analyses.

Reporting Groups
  Description
Rituximab 1000 mg (Stage I Patients) Stage I patients received 2 doses of rituximab 1000 mg administered intravenously (IV) 14 days apart at the beginning of the study (Days 1 and 15). During Weeks 24 to 40, patients who met disease activity and safety criteria were eligible to receive 2 additional IV infusions of rituximab 1000 mg given 14 days apart. Concomitant non-biological disease-modifying anti-rheumatic drug (DMARD) therapy, at a stable dose and route, was continued during the study, except for protocol defined prohibited DMARDs/combinations.
Rituximab 500 mg (Stage II Patients) Stage II patients received 2 doses of rituximab 500 mg administered intravenously (IV) 14 days apart at the beginning of the study (Days 1 and 15). During Weeks 24 to 40, patients who met disease activity and safety criteria were eligible to receive 2 additional IV infusions of rituximab 500 mg given 14 days apart. Concomitant biological and non-biological disease-modifying anti-rheumatic drug (DMARD) therapy, at a stable dose and route, was continued during the study, except for protocol defined prohibited DMARDs/combinations.

Participant Flow:   Overall Study
    Rituximab 1000 mg (Stage I Patients)     Rituximab 500 mg (Stage II Patients)  
STARTED     401     176  
Week 24     376     160  
Week 48     338     134  
COMPLETED     306 [1]   118 [1]
NOT COMPLETED     95     58  
Death                 1                 5  
Adverse Event                 5                 6  
Lost to Follow-up                 18                 12  
Patient's/Guardian's Decision                 58                 30  
Physician Decision                 13                 4  
Pregnancy                 0                 1  
[1] Completed the study or the safety follow-up 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.
No text entered.

Reporting Groups
  Description
Rituximab 1000 mg (Stage I Patients) Stage I patients received 2 doses of rituximab 1000 mg administered intravenously (IV) 14 days apart at the beginning of the study (Days 1 and 15). During Weeks 24 to 40, patients who met disease activity and safety criteria were eligible to receive 2 additional IV infusions of rituximab 1000 mg given 14 days apart. Concomitant non-biological disease-modifying anti-rheumatic drug (DMARD) therapy, at a stable dose and route, was continued during the study, except for protocol defined prohibited DMARDs/combinations.
Rituximab 500 mg (Stage II Patients) Stage II patients received 2 doses of rituximab 500 mg administered intravenously (IV) 14 days apart at the beginning of the study (Days 1 and 15). During Weeks 24 to 40, patients who met disease activity and safety criteria were eligible to receive 2 additional IV infusions of rituximab 500 mg given 14 days apart. Concomitant biological and non-biological disease-modifying anti-rheumatic drug (DMARD) therapy, at a stable dose and route, was continued during the study, except for protocol defined prohibited DMARDs/combinations.
Total Total of all reporting groups

Baseline Measures
    Rituximab 1000 mg (Stage I Patients)     Rituximab 500 mg (Stage II Patients)     Total  
Number of Participants  
[units: participants]
  401     176     577  
Age, Customized  
[units: Participants]
     
18 - 25 years     8     5     13  
26 - 35 years     22     8     30  
36 - 45 years     59     26     85  
46 - 55 years     132     48     180  
56 - 65 years     133     67     200  
66 - 75 years     38     19     57  
76 - 85 years     9     3     12  
> 85     0     0     0  
Gender  
[units: participants]
     
Female     302     154     456  
Male     99     22     121  



  Outcome Measures
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1.  Primary:   Percentage of Patients Developing a Serious Adverse Event (SAE) Within 24 Weeks After Receiving the First Course of Rituximab Treatment   [ Time Frame: From first treatment with rituximab (Day 1) through Week 24 ]

2.  Secondary:   Percentage of Patients Who Developed a Serious Adverse Event (SAE) During or Within 24 Hours of Rituximab Infusions   [ Time Frame: From start of rituximab treatment through 24 hours ]

3.  Secondary:   Percentage of Patients Who Developed a Serious Adverse Event (SAE) Within 24 Weeks After Receiving the Second Course (Optional Retreatment) of Rituximab Treatment   [ Time Frame: From start of the second course of rituximab treatment through Week 48 ]

4.  Secondary:   Percentage of Patients With an Improvement of 20%, 50%, and 70% in American College of Rheumatology (ACR) Scores (ACR20/50/70) From Baseline at Weeks 24 and 48   [ Time Frame: Baseline to Week 24 and Week 48 ]

5.  Secondary:   Percentage of Patients Achieving Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS 28-ESR) Remission and DAS 28-ESR Low Disease Activity Scores at Weeks 24 and 48   [ Time Frame: Week 24 and Week 48 ]

6.  Secondary:   Percentage of Patients With European League Against Rheumatism (EULAR) Good and Moderate Responses at Weeks 24 and 48   [ Time Frame: Baseline to Week 24 and Week 48 ]

7.  Secondary:   Health Assessment Questionnaire-Disability Index (HAQ-DI) Change From Baseline at Weeks 24 and 48   [ Time Frame: Baseline to Week 24 and Week 48 ]


  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: Genentech, Inc.
phone: 800-821-8590


No publications provided by Genentech, Inc.

Publications automatically indexed to this study:

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00443651     History of Changes
Other Study ID Numbers: U3924g
Study First Received: March 2, 2007
Results First Received: April 18, 2012
Last Updated: May 20, 2013
Health Authority: United States: Food and Drug Administration