A Study of RoActemra/Actemra and, if Initially Inadequately Responded to RoActemra/Actemra, Followed by MabThera/Rituxan in Patients With Rheumatoid Arthritis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01332994
First received: March 18, 2011
Last updated: August 5, 2015
Last verified: August 2015
Results First Received: August 5, 2015  
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 [MabThera/Rituxan]
Drug: tocilizumab [RoActemra/Actemra]

  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
After a screening period of up to 4 weeks, eligible participants were treated according to a predefined treatment algorithm based on disease response. In certain cases a re-screening was allowed. Participants were enrolled into the study with the administration of their first dose.

Reporting Groups
  Description
Tocilizumab (TCZ)/TCZ or TCZ/Rituximab (RTX) All participants were assigned to receive TCZ 8 milligrams per kilogram (mg/kg) via intravenous (IV) infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using Disease Activity Score Based on 28-Joint Count (DAS28) to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of less than (<) 2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score greater than (>) 1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score less than or equal to (≤) 1.2 or a score >3.2, received RTX 1000 milligrams (mg) via IV infusion at Weeks 16 and 18.

Participant Flow:   Overall Study
    Tocilizumab (TCZ)/TCZ or TCZ/Rituximab (RTX)  
STARTED     519  
Completed Week 16     463  
Completed Week 32 (TCZ/TCZ)     200  
Completed Week 32 (TCZ/RTX)     26  
Completed Week 66 (TCZ/RTX)     25  
COMPLETED     448  
NOT COMPLETED     71  
Adverse Event                 34  
Death                 1  
Lack of Efficacy                 1  
Lost to Follow-up                 4  
Protocol Violation                 6  
Withdrawal by Subject                 15  
Administrative Problem                 2  
Not Specified                 8  



  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.
Main Intent-to-Treat (ITT) Population: All participants who received at least one dose of TCZ.

Reporting Groups
  Description
TCZ/TCZ or TCZ/RTX All participants were assigned to receive TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 infusions from Baseline to Week 12. Clinical response was assessed at Week 16 using DAS28 to determine subsequent treatment assignment. Participants who achieved early remission, defined as a DAS28 score of <2.6, were transferred to clinical routine care and no longer received study medication. Participants who were considered partial responders, defined as a decrease from Baseline in DAS28 score >1.2 or a score between 2.6 and 3.2, inclusive, received TCZ 8 mg/kg via IV infusion every 4 weeks for a total of 4 additional infusions from Week 16 to 28. Those with assessed as having no response, defined as a decrease from Baseline in DAS28 score ≤1.2 or a score >3.2, received RTX 1000 mg via IV infusion at Weeks 16 and 18.

Baseline Measures
    TCZ/TCZ or TCZ/RTX  
Number of Participants  
[units: participants]
  519  
Age  
[units: years]
Mean (Standard Deviation)
  55.7  (11.9)  
Gender  
[units: participants]
 
Female     352  
Male     167  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Participants Achieving Remission at Week 16 According to DAS28   [ Time Frame: Week 16 ]

2.  Secondary:   Percentage of Participants Achieving Remission According to DAS28 at Weeks 4, 8, and 12   [ Time Frame: Weeks 4, 8, and 12 ]

3.  Secondary:   Percentage of Participants Achieving Remission According to DAS28 at Weeks 16, 20, 24, and 28 Among Participants Treated With 8 Courses of Tocilizumab   [ Time Frame: Weeks 16, 20, 24, and 28 ]

4.  Secondary:   Percentage of Participants Achieving Remission According to DAS28 at Week 32 Among Participants Treated With 8 Courses of Tocilizumab   [ Time Frame: Week 32 ]

5.  Secondary:   Percentage of Participants Achieving Remission According to DAS28 at Week 32 Among Nonresponding Participants Treated With Rituximab   [ Time Frame: Week 32 ]

6.  Secondary:   Percentage of Participants Achieving Low Disease Activity Score (LDAS) According to DAS28   [ Time Frame: Week 16 ]

7.  Secondary:   Percentage of Participants Achieving LDAS According to DAS28 Among Among Nonresponding Participants Treated With Rituximab   [ Time Frame: Week 32 ]

8.  Secondary:   Percentage of Participants Achieving a Clinically Relevant Reduction From Baseline in DAS28 at Week 16   [ Time Frame: Baseline and Week 16 ]

9.  Secondary:   Percentage of Participants Achieving a Clinically Relevant Reduction From Baseline in DAS28 at Weeks 4, 8, and 12   [ Time Frame: Baseline and Weeks 4, 8, and 12 ]

10.  Secondary:   Percentage of Participants Achieving a Clinically Relevant Reduction in DAS28 From Week 16 to Week 32 Among Nonresponding Participants Treated With Rituximab   [ Time Frame: Weeks 16 and 32 ]

11.  Secondary:   DAS28 Scores During and After Treatment   [ Time Frame: Baseline and Weeks 4, 8, 12, 16 ]

12.  Secondary:   DAS28 Scores During and After Treatment Among Participants Treated With 8 Courses of Tocilizumab   [ Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, and 32 ]

13.  Secondary:   DAS28 Scores During and After Treatment Among Nonresponding Participants Treated With Rituximab   [ Time Frame: Baseline and Weeks 4, 8, 12, 16, 24, and 32 ]

14.  Secondary:   DAS28 Scores During Safety Follow-Up Among Nonresponding Participants Treated With Rituximab   [ Time Frame: Weeks 40, 48, 56, and 66 ]

15.  Secondary:   Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Weeks 4, 8, 12 and 16   [ Time Frame: Baseline and Weeks 4, 8, 12, and 16 ]

16.  Secondary:   Percentage of Participants Achieving a Response According to EULAR Criteria at Week 32 Compared to Week 16 Among Nonresponding Participants Treated With Rituximab   [ Time Frame: Weeks 16 and 32 ]

17.  Secondary:   Percentage of Participants Achieving a Response According to EULAR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab   [ Time Frame: Baseline and Weeks 20, 24, 28, and 32 ]

18.  Secondary:   Percentage of Participants Achieving a Response According to American College of Rheumatology (ACR) Criteria at Weeks 4, 8, 12, and 16   [ Time Frame: Baseline and Weeks 4, 8, 12, and 16 ]

19.  Secondary:   Percentage of Participants Achieving a Response According to ACR Criteria at Week 32 Compared to Week 16 Among Nonresponding Participants Treated With Rituximab   [ Time Frame: Weeks 16 and 32 ]

20.  Secondary:   Percentage of Participants Achieving a Response According to ACR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab   [ Time Frame: Baseline and Weeks 20, 24, 28, and 32 ]

21.  Secondary:   Change From Baseline in Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) Scores at Weeks 4, 8, 12, and 16   [ Time Frame: Baseline and Weeks 4, 8, 12, and 16 ]

22.  Secondary:   Change From Week 16 to 32 in CDAI and SDAI Scores Among Nonresponding Participants Treated With Rituximab   [ Time Frame: Weeks 16 and 32 ]

23.  Secondary:   Change From Baseline in CDAI and SDAI Scores at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab   [ Time Frame: Baseline and Weeks 20, 24, 28, and 32 ]

24.  Secondary:   Change From Baseline in Hemoglobin at Weeks 4, 8, 12, and 16   [ Time Frame: Baseline and Weeks 4, 8, 12, and 16 ]

25.  Secondary:   Change From Baseline in CRP at Weeks 4, 8, 12, and 16   [ Time Frame: Baseline and Weeks 4, 8, 12, and 16 ]

26.  Secondary:   Change From Baseline in ESR at Weeks 4, 8, 12, and 16   [ Time Frame: Baseline and Weeks 4, 8, 12, and 16 ]

27.  Secondary:   Change in Hemoglobin From Week 16 to 32 Among Nonresponding Participants Treated With Rituximab   [ Time Frame: Weeks 16 and 32 ]

28.  Secondary:   Change in CRP From Week 16 to 32 Among Nonresponding Participants Treated With Rituximab   [ Time Frame: Weeks 16 and 32 ]

29.  Secondary:   Change in ESR From Week 16 to 32 Among Nonresponding Participants Treated With Rituximab   [ Time Frame: Weeks 16 and 32 ]

30.  Secondary:   Change From Baseline in Hemoglobin at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab   [ Time Frame: Baseline and Weeks 20, 24, 28, and 32 ]

31.  Secondary:   Change From Baseline in CRP at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab   [ Time Frame: Baseline and Weeks 20, 24, 28, and 32 ]

32.  Secondary:   Change From Baseline in ESR at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab   [ Time Frame: Baseline and Weeks 20, 24, 28, and 32 ]

33.  Secondary:   Percentage of Participants Withdrawing From the Study for Insufficient Therapeutic Response   [ Time Frame: Baseline to Week 16 ]

34.  Secondary:   Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants With Early Remission   [ Time Frame: Baseline ]

35.  Secondary:   Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants Treated With 8 Courses of Tocilizumab   [ Time Frame: Baseline ]

36.  Secondary:   Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Nonresponding Participants Treated With Rituximab   [ Time Frame: Baseline ]

37.  Secondary:   Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Week 16 Among Participants With Early Remission   [ Time Frame: Baseline and Week 16 ]

38.  Secondary:   Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab   [ Time Frame: Baseline and Weeks 16, 24, and 32 ]

39.  Secondary:   Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab   [ Time Frame: Baseline and Weeks 16, 32, 40, 48, and 66 ]

40.  Secondary:   Mean Number of Work Days Missed Per Week   [ Time Frame: Baseline and Week 16 ]

41.  Secondary:   Quality of Life as Assessed Using Short Form 36 (SF-36)   [ Time Frame: Baseline and Week 16 ]

42.  Secondary:   Change From Baseline in Quality of Life as Assessed Using SF-36 at Week 16   [ Time Frame: Baseline and Week 16 ]

43.  Secondary:   Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Participants Treated With 8 Courses of Tocilizumab   [ Time Frame: Weeks 16 and 32 ]

44.  Secondary:   Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Nonresponding Participants Treated With Rituximab   [ Time Frame: Weeks 16 and 32 ]

45.  Secondary:   Quality of Life as Assessed Using HAQ-DI   [ Time Frame: Baseline and Week 16 ]

46.  Secondary:   Change From Baseline in Quality of Life as Assessed Using HAQ-DI at Week 16   [ Time Frame: Baseline and Week 16 ]

47.  Secondary:   Change From Week 16 to 32 in Quality of Life as Assessed Using HAQ-DI Among Participants Treated With 8 Courses of Tocilizumab   [ Time Frame: Weeks 16 and 32 ]

48.  Secondary:   Change From Week 16 to 32 in Quality of Life as Assessed Using HAQ-DI Among Nonresponding Participants Treated With Rituximab   [ Time Frame: Weeks 16 and 32 ]

49.  Secondary:   Percentage of Participants Achieving a Response According to HAQ-DI Criteria   [ Time Frame: Baseline and Week 16 ]

50.  Secondary:   Quality of Life as Assessed Using Functional Assessment of Chronic Illness Therapy (FACIT)   [ Time Frame: Baseline and Week 16 ]

51.  Secondary:   Change From Baseline in Quality of Life as Assessed Using FACIT at Week 16   [ Time Frame: Baseline and Week 16 ]

52.  Secondary:   Change From Week 16 to 32 in Quality of Life as Assessed Using FACIT Among Participants Treated With 8 Courses of Tocilizumab   [ Time Frame: Weeks 16 and 32 ]

53.  Secondary:   Change From Week 16 to 32 in Quality of Life as Assessed Using FACIT Among Nonresponding Participants Treated With Rituximab   [ Time Frame: Weeks 16 and 32 ]


  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-LaRoche
phone: 800-821-8590
e-mail: genentech@druginfo.com


No publications provided


Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01332994     History of Changes
Other Study ID Numbers: ML22985
Study First Received: March 18, 2011
Results First Received: August 5, 2015
Last Updated: August 5, 2015
Health Authority: Germany: Paul-Ehrlich-Institut