A Study to Evaluate Rituximab in Combination With Methotrexate Compared to Methotrexate Alone in Patients With Rheumatoid Arthritis (SERENE)

This study has been completed.
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
Genentech
ClinicalTrials.gov Identifier:
NCT00299130
First received: March 3, 2006
Last updated: June 10, 2014
Last verified: June 2014
Results First Received: February 21, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Rheumatoid Arthritis
Interventions: Drug: Folate
Drug: Methotrexate
Drug: Methylprednisolone
Drug: Placebo
Drug: Rituximab

  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
A total of 511 patients were recruited and randomized between 25 October 2005 and 15 November 2006.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
One patient was randomized first to the rituximab 1000 mg + methotrexate (MTX) arm and then to the rituximab 500 mg + MTX arm. No assessments were recorded or medication given after the first randomization and all data used in the analyses was following the second randomization, so the participant is included only in the rituximab 500 mg + MTX arm.

Reporting Groups
  Description
Placebo + MTX

Participants received placebo intravenous infusion on Days 1 and 15. After Week 24, participants could switch to receive rituximab 500 mg (on Days 1 and 15) every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Placebo and rituximab infusions were preceded with 100 mg intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of methotrexate (MTX) and ≥ 5 mg/week folic acid for the duration of their participation in the study.

All participants entered a 48-week safety follow-up (SFU) period following the treatment period.

Rituximab 500 mg + MTX

Participants received 500 mg rituximab administered by intravenous infusion on Days 1 and 15. After Week 24, participants received further courses of rituximab every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Rituximab infusions were preceded with 100 mg intravenous methylprednisolone.

Participants also received a stable dose of 10-25 mg/week of methotrexate and ≥ 5 mg/week folic acid for the duration of their participation in the study.

All participants entered a 48-week safety follow-up (SFU) period following the treatment period.

Rituximab 1000 mg + MTX

Participants received 1000 mg rituximab administered by intravenous infusion on Days 1 and 15. After Week 24, participants received further courses of rituximab every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Rituximab infusions were preceded with 100 mg intravenous methylprednisolone.

Participants also received a stable dose of 10-25 mg/week of methotrexate and ≥ 5 mg/week folic acid for the duration of their participation in the study.

All participants entered a 48-week safety follow-up (SFU) period following the treatment period.


Participant Flow for 3 periods

Period 1:   Treatment Period
    Placebo + MTX     Rituximab 500 mg + MTX     Rituximab 1000 mg + MTX  
STARTED     172     168     171  
Treated     172 [1]   167     170  
Completed 24 Weeks     159     162     166  
Completed 48 Weeks     155     157     158  
Completed 144 Weeks     133     138     132  
COMPLETED     119     125     121  
NOT COMPLETED     53     43     50  
Adverse Event                 13                 8                 13  
Death                 1                 3                 1  
Insufficient Therapeutic Response                 19                 6                 6  
Protocol Violation                 0                 1                 0  
Refused Treatment                 12                 12                 19  
Failure to Return                 4                 6                 6  
Reason not Specified                 4                 6                 4  
Withdrawal by Subject                 0                 1                 1  
[1] 155 patients in the placebo arm switched to active therapy with rituximab 2x500mg between Week 24-72

Period 2:   Safety Follow-up Period
    Placebo + MTX     Rituximab 500 mg + MTX     Rituximab 1000 mg + MTX  
STARTED     167     165     168  
COMPLETED     122     120     123  
NOT COMPLETED     45     45     45  
Administrative/Other                 4                 9                 4  
Death                 4                 5                 3  
Did not Co-operate                 1                 1                 2  
Failure to Return                 14                 7                 15  
No SFU Week 48 Date Recorded                 0                 1                 0  
Withdrawal by Subject                 22                 22                 21  

Period 3:   Extended Safety Follow-up Period
    Placebo + MTX     Rituximab 500 mg + MTX     Rituximab 1000 mg + MTX  
STARTED     0     82     44  
COMPLETED     0     74     38  
NOT COMPLETED     0     8     6  
Death                 0                 3                 0  
Failure to Return                 0                 2                 2  
Did not Cooperate/Withdrew Consent                 0                 3                 4  



  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
Placebo + MTX

Participants received placebo intravenous infusion on Days 1 and 15. After Week 24, participants could switch to receive rituximab 500 mg (on Days 1 and 15) every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Placebo and rituximab infusions were preceded with 100 mg intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of methotrexate (MTX) and ≥ 5 mg/week folic acid for the duration of their participation in the study.

All participants entered a 48-week safety follow-up (SFU) period following the treatment period.

Rituximab 500 mg + MTX

Participants received 500 mg rituximab administered by intravenous infusion on Days 1 and 15. After Week 24, participants received further courses of rituximab every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Rituximab infusions were preceded with 100 mg intravenous methylprednisolone.

Participants also received a stable dose of 10-25 mg/week of methotrexate and ≥ 5 mg/week folic acid for the duration of their participation in the study.

All participants entered a 48-week safety follow-up (SFU) period following the treatment period.

Rituximab 1000 mg + MTX

Participants received 1000 mg rituximab administered by intravenous infusion on Days 1 and 15. After Week 24, participants received further courses of rituximab every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Rituximab infusions were preceded with 100 mg intravenous methylprednisolone.

Participants also received a stable dose of 10-25 mg/week of methotrexate and ≥ 5 mg/week folic acid for the duration of their participation in the study.

All participants entered a 48-week safety follow-up (SFU) period following the treatment period.

Total Total of all reporting groups

Baseline Measures
    Placebo + MTX     Rituximab 500 mg + MTX     Rituximab 1000 mg + MTX     Total  
Number of Participants  
[units: participants]
  172     167     170     509  
Age  
[units: years]
Mean ± Standard Deviation
  52.16  ± 12.390     51.91  ± 12.926     51.30  ± 12.644     51.8  ± 12.64  
Gender  
[units: participants]
       
Female     147     133     138     418  
Male     25     34     32     91  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 24   [ Time Frame: Baseline and Week 24 ]

2.  Secondary:   Percentage of Participants With an ACR50 Response at Week 24   [ Time Frame: Baseline and Week 24 ]

3.  Secondary:   Percentage of Participants With an ACR70 Response at Week 24   [ Time Frame: Baseline and Week 24 ]

4.  Secondary:   Change From Baseline in Disease Activity Score (DAS28-ESR) at Week 24   [ Time Frame: Baseline and Week 24 ]

5.  Secondary:   Percentage of Participants With European League Against Rheumatism (EULAR) Response at Week 24   [ Time Frame: Baseline and Week 24 ]

6.  Secondary:   Percent Change From Baseline in Swollen Joint Count   [ Time Frame: Baseline, Week 24 and Week 48 ]

7.  Secondary:   Percent Change From Baseline in Tender Joint Count   [ Time Frame: Baseline, Week 24 and Week 48 ]

8.  Secondary:   Percent Change From Baseline in Patient's Global Assessment of Disease Activity   [ Time Frame: Baseline, Week 24 and Week 48 ]

9.  Secondary:   Percent Change From Baseline in Patient’s Pain Assessment   [ Time Frame: Baseline, Week 24 and Week 48 ]

10.  Secondary:   Percent Change From Baseline in Physician’s Global Assessment of Disease Activity   [ Time Frame: Baseline, Week 24 and Week 48 ]

11.  Secondary:   Percent Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score   [ Time Frame: Baseline, Week 24 and Week 48 ]

12.  Secondary:   Percent Change From Baseline in C-Reactive Protein   [ Time Frame: Baseline, Week 24 and Week 48 ]

13.  Secondary:   Percent Change From Baseline in Erythrocyte Sedimentation Rate   [ Time Frame: Baseline, Week 24 and Week 48 ]

14.  Secondary:   Percent Change From Baseline in Short Form 36 Health Survey (SF-36)   [ Time Frame: Baseline, Week 24 and Week 48 ]

15.  Secondary:   Change From Baseline in Short Form 36 Health Survey (SF-36) General Health Domain Score   [ Time Frame: Baseline, Week 24 and Week 48 ]

16.  Secondary:   Change From Baseline in Short Form 36 Health Survey (SF-36) Bodily Pain Domain Score   [ Time Frame: Baseline, Week 24 and Week 48 ]

17.  Secondary:   Change From Baseline in Short Form 36 Health Survey (SF-36) Physical Functioning Domain Score   [ Time Frame: Baseline, Week 24 and Week 48 ]

18.  Secondary:   Change From Baseline in Short Form 36 Health Survey (SF-36) Physical Role Limitations Domain Score   [ Time Frame: Baseline, Week 24 and Week 48 ]

19.  Secondary:   Change From Baseline in Short Form 36 Health Survey (SF-36) Mental Health Domain Score   [ Time Frame: Baseline, Week 24 and Week 48 ]

20.  Secondary:   Change From Baseline in Short Form 36 Health Survey (SF-36) Vitality Domain Score   [ Time Frame: Baseline, Week 24 and Week 48 ]

21.  Secondary:   Change From Baseline in Short Form 36 Health Survey (SF-36) Social Functioning Domain Score   [ Time Frame: Baseline, Week 24 and Week 48 ]

22.  Secondary:   Change From Baseline in Short Form 36 Health Survey (SF-36) Emotional Role Limitations Domain Score   [ Time Frame: Baseline, Week 24 and Week 48 ]

23.  Secondary:   Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Scores   [ Time Frame: Baseline, Week 24 and Week 48 ]

24.  Secondary:   Percentage of Participants With DAS28-ESR Low Disease Activity Score and Clinical Remission at Week 24   [ Time Frame: Week 24 ]

25.  Secondary:   Percentage of Participants With HAQ-DI Improved, Unchanged or Worsened at Week 24   [ Time Frame: Baseline and Week 24 ]

26.  Secondary:   Percentage of Participants With HAQ-DI Improved, Unchanged or Worsened at Week 48   [ Time Frame: Baseline and Week 48 ]

27.  Secondary:   Percentage of Participants With European League Against Rheumatism (EULAR) Response at Week 48   [ Time Frame: Baseline and Week 48 ]

28.  Secondary:   Percentage of Participants With DAS28-ESR Low Disease Activity Score and Clinical Remission at Week 48   [ Time Frame: Week 48 ]

29.  Secondary:   Percentage of Participants With an ACR50 Response at Week 48   [ Time Frame: Baseline and Week 48 ]

30.  Secondary:   Percentage of Participants With an ACR70 Response at Week 48   [ Time Frame: Baseline and Week 48 ]

31.  Secondary:   Time to Repletion of Peripheral CD19+ B-cells   [ Time Frame: Beginning of the first infusion (Day 1) in the last treatment cycle until repletion or the end of the study (up to 3 years, 6 months) ]

32.  Secondary:   Percentage of Participants With Low Immunoglobulin Concentrations Post-rituximab Treatment   [ Time Frame: Beginning of the safety follow-up period to the end of the study (up to 3 years) ]


  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: Hoffman-LaRoche
phone: 800-821-8590


No publications provided by Genentech

Publications automatically indexed to this study:

Responsible Party: Genentech
ClinicalTrials.gov Identifier: NCT00299130     History of Changes
Other Study ID Numbers: U2973g, WA17045
Study First Received: March 3, 2006
Results First Received: February 21, 2013
Last Updated: June 10, 2014
Health Authority: United States: Food and Drug Administration