A Study of the Safety and Efficacy of Golimumab in Subjects With Rheumatoid Arthritis That Are Methotrexate-Naive - Study Results

Study Type:	Interventional
Study Design:	Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment
Condition:	Rheumatoid Arthritis
Interventions:	Biological: golimumab Drug: placebo; methotrexate Drug: golimumab; methotrexate Biological: Golimumab

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This was a multicenter, randomized, double-blind, placebo-controlled, 4-arm, parallel-group study with the first patient consented on 12Dec2005. The Week 24 database lock was 01 Oct. 2007. 637 subjects were randomized at 90 centers: 25 sites in Asia, 34 sites in Europe/Australia/New Zealand, 10 sites in Latin America and 21 sites in North America.

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 I: Placebo + Methotrexate (MTX)	Placebo SC injections every 4 wks from Wk 0 to Wk 48 (unless early escape at Wk 28); MTX - 10 to 20 mg from Wk 0 for up to 5 years; golimumab - If early escape, 50 mg SC injection every 4 wks from Wk 28 up to 5 yrs; golimumab - Dr's discretion after unblinding (last patients enrolled completes the Wk 52 evaluation and database is locked), dose adjust from 50 to 100 mg.
Group II: Golimumab 100 mg + Placebo	Golimumab 100 mg SC injection every 4 wks from Wk 0 for up to 5 yrs, placebo capsule MTX weekly from Wk 0 to unblinding (last patients enrolled completes the Wk 52 evaluation and database is locked) unless early escape at Wk 28; MTX - If early escape start 10 mg weekly during blinded period; MTX - Dr's discretion, adjust weekly dose after unblinding.
Group III: Golimumab 50 mg + Methotrexate (MTX)	Golimumab 50 mg SC injections every 4 wks from Wk 0-48 (Wk 28 if early escape); MTX - 10 to 20 mg from Wk 0 for up to 5 years; golimumab - If early escape, 100 mg beginning at Wk 28 for up to 5 yrs; golimumab - Dr's discretion after unblinding (last patients enrolled completes the Wk 52 evaluation and database is locked), dose adjust from 50 to 100 mg.
Group IV: Golimumab 100 mg + Methotrexate (MTX)	Golimumab 100 mg SC injections every 4 wks from Wk 0 up to 5 yrs; MTX - 10 to 20 mg from Wk 0 for up to 5 years.

Participant Flow: Overall Study

	Group I: Placebo + Methotrexate (MTX)	Group II: Golimumab 100 mg + Placebo	Group III: Golimumab 50 mg + Methotrexate (MTX)	Group IV: Golimumab 100 mg + Methotrexate (MTX)
STARTED	160	159	159	159
COMPLETED	150^[1]	150^[2]	151^[3]	149^[4]
NOT COMPLETED	10	9	8	10
Adverse Event	1	1	5	6
Unsatisfactory theapeutic effect	1	3	0	0
Lost to Follow-up	3	0	1	1
Death	0	0	1	1
Patient relocated	1	0	0	0
Not specified	4	5	1	2

[1]	Indicates number of patients that are continuing subcutaneous study agent at Week 24
[2]	Indicates number of patients that are continuing subcutaneous study agent at Week 24
[3]	Indicates number of patients that are continuing subcutaneous study agent at Week 24
[4]	Indicates number of patients that are continuing subcutaneous study agent at Week 24

Baseline Characteristics

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Reporting Groups

	Description
Group I: Placebo + Methotrexate (MTX)	Placebo SC injections every 4 wks from Wk 0 to Wk 48 (unless early escape at Wk 28); MTX - 10 to 20 mg from Wk 0 for up to 5 years; golimumab - If early escape, 50 mg SC injection every 4 wks from Wk 28 up to 5 yrs; golimumab - Dr's discretion after unblinding (last patients enrolled completes the Wk 52 evaluation and database is locked), dose adjust from 50 to 100 mg.
Group II: Golimumab 100 mg + Placebo	Golimumab 100 mg SC injection every 4 wks from Wk 0 for up to 5 yrs, placebo capsule MTX weekly from Wk 0 to unblinding (last patients enrolled completes the Wk 52 evaluation and database is locked) unless early escape at Wk 28; MTX - If early escape start 10 mg weekly during blinded period; MTX - Dr's discretion, adjust weekly dose after unblinding.
Group III: Golimumab 50 mg + Methotrexate (MTX)	Golimumab 50 mg SC injections every 4 wks from Wk 0-48 (Wk 28 if early escape); MTX - 10 to 20 mg from Wk 0 for up to 5 years; golimumab - If early escape, 100 mg beginning at Wk 28 for up to 5 yrs; golimumab - Dr's discretion after unblinding (last patients enrolled completes the Wk 52 evaluation and database is locked), dose adjust from 50 to 100 mg.
Group IV: Golimumab 100 mg + Methotrexate (MTX)	Golimumab 100 mg SC injections every 4 wks from Wk 0 up to 5 yrs; MTX - 10 to 20 mg from Wk 0 for up to 5 years.

Baseline Measures

	Group I: Placebo + Methotrexate (MTX)	Group II: Golimumab 100 mg + Placebo	Group III: Golimumab 50 mg + Methotrexate (MTX)	Group IV: Golimumab 100 mg + Methotrexate (MTX)	Total
Number of Participants [units: participants]	160	159	159	159	637
Age [units: years] Mean ± Standard Deviation	48.6 ± 12.91	48.2 ± 12.85	50.9 ± 11.32	50.2 ± 11.87	49.5 ± 12.28
Gender [units: participants]
Female	134	134	135	125	528
Male	26	25	24	34	109

Outcome Measures

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1. Primary:

American College of Rheumatology 50 Response at Week 24 [ Week 24 ]

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2. Secondary:

American College of Rheumatology 20 Response at Week 24 [ Week 24 ]

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Measure Type	Secondary
Measure Title	American College of Rheumatology 20 Response at Week 24
Measure Description	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	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.
Intent to Treat (ITT). Patients considered non-responder if used any pre-specified prohibited medications or discontinued subcutaneous (SC) study agent due to lack of efficacy. Missing ACR components were imputed by Last Observation Carried Forward (LOCF) unless all ACR components are missing in which case considered non-responders.

Reporting Groups

	Description
Group I: Placebo + Methotrexate (MTX)	Placebo SC injections every 4 wks from Wk 0 to Wk 48 (unless early escape at Wk 28); MTX - 10 to 20 mg from Wk 0 for up to 5 years; golimumab - If early escape, 50 mg SC injection every 4 wks from Wk 28 up to 5 yrs; golimumab - Dr's discretion after unblinding, dose adjust from 50 to 100 mg.
Group II: Golimumab 100 mg + Placebo	Golimumab 100 mg SC injection every 4 wks from Wk 0 for up to 5 yrs, placebo capsule MTX weekly from Wk 0 to unblinding (last patients enrolled completes the Wk 52 evaluation and database is locked) unless early escape at Wk 28; MTX - If early escape start 10 mg weekly during blinded period; MTX - Dr's discretion, adjust weekly dose after unblinding.
Group III: Golimumab 50 mg + Methotrexate (MTX)	Golimumab 50 mg SC injections every 4 wks from Wk 0-48 (Wk 28 if early escape); MTX - 10 to 20 mg from Wk 0 for up to 5 years; golimumab - If early escape, 100 mg beginning at Wk 28 for up to 5 yrs; golimumab - Dr's discretion after unblinding, dose adjust from 50 to 100 mg.
Group IV: Golimumab 100 mg + Methotrexate (MTX)	Golimumab 100 mg SC injections every 4 wks from Wk 0 up to 5 yrs; MTX - 10 to 20 mg from Wk 0 for up to 5 years.
Combined: Group III & IV	Combines Group III (golimumab 50 mg + methotrexate (MTX)) and Group IV (golimumab 100 mg + MTX)

Measured Values

	Group I: Placebo + Methotrexate (MTX)	Group II: Golimumab 100 mg + Placebo	Group III: Golimumab 50 mg + Methotrexate (MTX)	Group IV: Golimumab 100 mg + Methotrexate (MTX)	Combined: Group III & IV
Number of Participants Analyzed [units: participants]	160	159	159	159	318
American College of Rheumatology 20 Response at Week 24 [units: Participants]	79	82	98	98	196

Statistical Analysis 1 for American College of Rheumatology 20 Response at Week 24

Groups ^[1]	Group I: Placebo + Methotrexate (MTX) vs. Combined: Group III & IV
Method ^[2]	Cochran-Mantel-Haenszel
P Value ^[3]	0.011

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	Cochran-Mantel-Haenszel(CMH) test stratified by screening C-reactive protein (CRP) (< 1.5 mg/dL; >= 1.5 mg/dL)
[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 20 Response at Week 24

Groups ^[1]	Group I: Placebo + Methotrexate (MTX) vs. Group III: Golimumab 50 mg + Methotrexate (MTX)
Method ^[2]	Cochran-Mantel-Haenszel
P Value ^[3]	0.028

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	CMH test stratified by screening CRP (< 1.5 mg/dL; >= 1.5 mg/dL)
[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 3 for American College of Rheumatology 20 Response at Week 24

Groups ^[1]	Group I: Placebo + Methotrexate (MTX) vs. Group IV: Golimumab 100 mg + Methotrexate (MTX)
Method ^[2]	Cochran-Mantel-Haenszel
P Value ^[3]	0.028

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	CMH test stratified by screening CRP (< 1.5 mg/dL; >= 1.5 mg/dL)
[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 4 for American College of Rheumatology 20 Response at Week 24

Groups ^[1]	Group I: Placebo + Methotrexate (MTX) vs. Group II: Golimumab 100 mg + Placebo
Method ^[2]	Cochran-Mantel-Haenszel
P Value ^[3]	0.677

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	CMH test stratified by screening CRP (< 1.5 mg/dL; >= 1.5 mg/dL)
[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.

3. Secondary:

American College of Rheumatology 50 Response at Week 24 in Patients With Abnormal C-reactive Protein at Baseline [ Week 24 ]

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Serious Adverse Events

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Other Adverse Events

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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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Generally, the only disclosure restriction on the PI is that the sponsor has 60 days to review results communications prior to public release and can embargo communications regarding trial results for a period that does not exceed 180 days from the time submitted to the sponsor for review. 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: Director Clinical Research
Organization: Centocor Research & Development, Inc.
phone: 1-800-457-6399

No publications provided

Responsible Party:	Centocor Inc. ( Director of Clinical Research )
Study ID Numbers:	CR006331, C0524T05, GO-BEFORE
Study First Received:	December 11, 2005
Results First Received:	May 21, 2009
Last Updated:	May 21, 2009
ClinicalTrials.gov Identifier:	NCT00264537 History of Changes
Health Authority:	United States: Food and Drug Administration