A Study of the Safety and Efficacy of Golimumab (CNTO 148) in Subjects With Active Rheumatoid Arthritis Previously Treated With Biologic Anti-TNFa Agent(s)

This study has been completed.
Sponsor:
Collaborator:
Schering-Plough
Information provided by (Responsible Party):
Centocor, Inc.
ClinicalTrials.gov Identifier:
NCT00299546
First received: March 3, 2006
Last updated: January 27, 2014
Last verified: January 2014
Results First Received: May 21, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Arthritis, Rheumatoid
Interventions: Drug: Placebo
Biological: Golimumab 50 mg
Biological: Golimumab 100 mg

  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 461 participants were enrolled at 86 sites in North America, Europe, Australia and New Zealand.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Group 1: Placebo Placebo Subcutaneous (SC) injections every 4 weeks (wks) thru Wk 20 (unless early escape at Wk 16); Golimumab - if early escape, 50 mg SC injections from Wk 16 up to 5 yrs; Golimumab - 50 mg SC injections beginning Wk 24 up to 5 yrs (unless early escape); Golimumab - Dr's discretion after unblinding, dose adjusted from 50 to 100 mg and from 100 to 50mg. Duration of the blinded period was until the week-24 database lock.
Group 2: Golimumab 50 mg Golimumab 50 mg SC injections every 4 wks from Wk 0 up to 5 yrs (unless early escape at Wk 16); Golimumab - if early escape, 100 mg SC injections every 4 wks beginning Wk 16 up to 5 yrs; Golimumab - Dr's discretion after unblinding, dose adjusted from 50 to 100 mg and from 100 to 50mg. Duration of the blinded period was until the week-24 database lock.
Group 3: Golimumab 100 mg Golimumab 100 mg SC injections every 4 wks from Wk 0 up to 5 yrs; Golimumab - Dr's discretion after unblinding, dose adjusted from 100 to 50 mg. Duration of the blinded period was until the week-24 database lock.

Participant Flow:   Overall Study
    Group 1: Placebo     Group 2: Golimumab 50 mg     Group 3: Golimumab 100 mg  
STARTED     155     153     153  
COMPLETED     55     61     67  
NOT COMPLETED     100     92     86  
Death                 3                 2                 0  
Lost to Follow-up                 2                 2                 5  
Adverse Event                 37                 22                 27  
Unsatisfactory therapeutic effect                 34                 39                 34  
Not specified                 24                 26                 19  
Not treated                 0                 1                 1  



  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
Group 1: Placebo Placebo Subcutaneous (SC) injections every 4 weeks (wks) thru Wk 20 (unless early escape at Wk 16); Golimumab - if early escape, 50 mg SC injections from Wk 16 up to 5 yrs; Golimumab - 50 mg SC injections beginning Wk 24 up to 5 yrs (unless early escape); Golimumab - Dr's discretion after unblinding, dose adjusted from 50 to 100 mg and from 100 to 50mg. Duration of the blinded period was until the week-24 database lock.
Group 2: Golimumab 50 mg Golimumab 50 mg SC injections every 4 wks from Wk 0 up to 5 yrs (unless early escape at Wk 16); Golimumab - if early escape, 100 mg SC injections every 4 wks beginning Wk 16 up to 5 yrs; Golimumab - Dr's discretion after unblinding, dose adjusted from 50 to 100 mg and from 100 to 50mg. Duration of the blinded period was until the week-24 database lock.
Group 3: Golimumab 100 mg Golimumab 100 mg SC injections every 4 wks from Wk 0 up to 5 yrs; Golimumab - Dr's discretion after unblinding, dose adjusted from 100 to 50 mg. Duration of the blinded period was until the week-24 database lock.
Total Total of all reporting groups

Baseline Measures
    Group 1: Placebo     Group 2: Golimumab 50 mg     Group 3: Golimumab 100 mg     Total  
Number of Participants  
[units: participants]
  155     153     153     461  
Age  
[units: years]
Mean ± Standard Deviation
  54.8  ± 13.07     53.9  ± 11.47     53.7  ± 12.26     54.1  ± 12.27  
Gender  
[units: participants]
       
Female     132     113     122     367  
Male     23     40     31     94  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   American College of Rheumatology (ACR) 20 Response at Week 14.   [ Time Frame: Week 14 ]

2.  Secondary:   American College of Rheumatology (ACR) 50 Response at Week 14   [ Time Frame: Week 14 ]

3.  Secondary:   Disease Activity Index Score 28 (DAS 28) (Using C-reactive Protein) Response at Week 14   [ Time Frame: Week 14 ]

4.  Secondary:   American College of Rheumatology (ACR) 20 at Week 24   [ Time Frame: From Baseline to Week 24 ]
  Hide Outcome Measure 4

Measure Type Secondary
Measure Title American College of Rheumatology (ACR) 20 at Week 24
Measure Description Number of patients who achieved ACR 20 response at Week (Wk) 24. ACR 20 response is an improvement of >= 20% from baseline in both the tender and swollen joint count and in at least 3 of the 5 assessments ( patient's assessment of pain visual analog scale (VAS), patient's global assessemnt of disease activity VAS scale, Physician's global assessment of disease activity VAS scale,HAQ and CRP)
Time Frame From Baseline to Week 24  
Safety Issue No  

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.
Randomized participants (excluding 1 site). Participants considered non-responders if used any prohibited medications or discontinued SC study agent due to lack of efficacy. Missing ACR components imputed by LOCF unless all components were missing; in which case considered non-responders. Wk 16 ACR response used for change in study tx.

Reporting Groups
  Description
Group 1: Placebo Placebo Subcutaneous (SC) injections every 4 weeks (wks) thru Wk 20 (unless early escape at Wk 16); golimumab - if early escape, 50 mg SC injections from Wk 16 up to 5 yrs; golimumab - 50 mg SC injections beginning Wk 24 up to 5 yrs (unless early escape); golimumab - Dr's discretion after unblinding, dose adjusted from 50 to 100 mg. Duration of the blinded period was until the week-24 database lock.
Group 2: Golimumab 50 mg Golimumab 50 mg SC injections every 4 wks from Wk 0 up to 5 yrs (unless early escape at Wk 16); golimumab - if early escape, 100 mg SC injections every 4 wks beginning Wk 16 up to 5 yrs; golimumab - Dr's discretion after unblinding, dose adjusted from 50 to 100 mg. Duration of the blinded period was until the week-24 database lock.
Group 3: Golimumab 100 mg Golimumab 100 mg SC injections every 4 wks from Wk 0 up to 5 yrs; Golimumab - Dr's discretion after unblinding, dose adjusted from 100 to 50 mg. Duration of the blinded period was until the week-24 database lock.
Combined Golimumab Combines Group 2 (golimumab 50 mg) and Group 3 (golimumab 100 mg).

Measured Values
    Group 1: Placebo     Group 2: Golimumab 50 mg     Group 3: Golimumab 100 mg     Combined Golimumab  
Number of Participants Analyzed  
[units: participants]
  150     147     148     295  
American College of Rheumatology (ACR) 20 at Week 24  
[units: participants]
  24     46     63     109  


Statistical Analysis 1 for American College of Rheumatology (ACR) 20 at Week 24
Groups [1] Group 1: Placebo vs. Combined Golimumab
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Stratified by baseline Methotrexate (MTX).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.

Statistical Analysis 2 for American College of Rheumatology (ACR) 20 at Week 24
Groups [1] Group 1: Placebo vs. Group 2: Golimumab 50 mg
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.002
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Stratified by baseline MTX.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Test was performed because Group 1: Placebo was significantly different from Combined Groups 2 & 3.

Statistical Analysis 3 for American College of Rheumatology (ACR) 20 at Week 24
Groups [1] Group 1: Placebo vs. Group 3: Golimumab 100 mg
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Stratified by baseline MTX.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Test was performed because Group 1: Placebo was significantly different from Combined Groups 2 & 3.



5.  Secondary:   Health Assessment Questionnaire (HAQ) Score at Week 24   [ Time Frame: From Baseline to Week 24 ]


  Serious Adverse Events


  Other Adverse Events


  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.


Limitations and Caveats
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
The count of patients with any nonserious adverse events (NAE) excludes patients who only had NAE that occurred in <= 5% of patients. This information may vary from existing approved labeling and publications due to the requirement of this website.  


Results Point of Contact:  
Name/Title: Associate Director Clinical Research
Organization: Centocor Research & Development, Inc.
phone: 1-800-457-6399


No publications provided by Centocor, Inc.

Publications automatically indexed to this study:

Responsible Party: Centocor, Inc.
ClinicalTrials.gov Identifier: NCT00299546     History of Changes
Other Study ID Numbers: CR006334, C0524T11
Study First Received: March 3, 2006
Results First Received: May 21, 2009
Last Updated: January 27, 2014
Health Authority: United States: Food and Drug Administration