Golimumab in Rheumatoid Arthritis Participants With an Inadequate Response to Etanercept (ENBREL) or Adalimumab (HUMIRA)

• Sponsor: Janssen Biotech, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01004432
• Collaborator: Merck Sharp & Dohme LLC (Industry)
• Enrollment: 433
• Locations: 117
• Arms: 5
• Duration (Months): 46
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of switching rheumatoid arthritis (RA) participants who have an inadequate response to their current treatment with either etanercept + methotrexate or adalimumab + methotrexate to treatment with golimumab 50 milligram (mg) subcutaneous (SC) injection (a needle inserted under the skin in the back of upper arm, upper thigh or stomach area) every 4 weeks + methotrexate. This study is also designed to evaluate the benefit and safety of switching participants from treatment with golimumab 50 mg subcutaneous injection every 4 weeks + methotrexate to golimumab 2 milligram per kilogram (mg/kg) intravenous every 8 weeks + methotrexate, for those who do not achieve a marked improvement of their RA at Week 16.

Condition or Disease	Intervention/Treatment	Phase
Arthritis; Arthritis, Rheumatoid; Autoimmune Diseases	Drug: Golimumab 50 mg SC; Drug: Golimumab 2 mg/kg IV; Drug: Methotrexate (MTX); Drug: Placebo SC; Drug: Placebo IV	Phase 3

Detailed Description

The study consists of a main study and a voluntary, open-label (participants and researchers are aware about the treatment participants are receiving), 24-week study extension. The main study includes a Screening Run-in Period (Week -6 to Week 0), an Open-label Treatment Period (Week 0 to Week 16), an Open-label or Double-blind Treatment Period (Week 16 to Week 52). The main study also includes a Follow-up Period from Week 52 through Week 64 for those participants who will not participate in the 24-week study extension. Participants, participating in 24-week extension (at Week 52), will receive open-label golimumab SC injections every 4 weeks from Week 52 up to Week 72 and will be followed-up up to Week 88. All eligible participants will initiate the treatment with open-label golimumab SC injection every 4 weeks up to Week 12. At Week 16, depending upon the treatment response either participants will continue to receive open-label golimumab SC injection every 4 weeks up to Week 48 or participants will be randomly assigned to receive following 2 treatments: 1- golimumab 50mg SC injection every 4 weeks along with placebo intravenous infusion every 8 weeks through Week 48; 2- Placebo SC injection every 4 weeks along with golimumab 2mg/kg intravenous infusion every 8 weeks through Week 48. At Week 52, participants who choose to participate in the 24-week study extension will receive open-label golimumab 50 mg SC injections every 4 weeks through Week 72. Participants' safety will be monitored throughout the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 433 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Golimumab Phase 3b, Multicenter, Switch Assessment of Subcutaneous and Intravenous Efficacy in Rheumatoid Arthritis Patients Who Have Inadequate Disease Control Despite Treatment With Etanercept (ENBREL) or Adalimumab (HUMIRA)
• Study Start Date: Dec 1, 2009
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: Oct 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Open-label (OL) Overall Group: Golimumab 50 mg SC + MTX All enrolled and dosed participants receive golimumab 50 milligram (mg) subcutaneous (SC) injection every 4 weeks + Methotrexate (MTX) from Week 0 to Week 12.	Drug: Golimumab 50 mg SC; Golimumab 50 milligram (mg) subcutaneous (SC) injection every 4 weeks.; Drug: Methotrexate (MTX); Participants will continue taking their current Methotrexate (MTX) treatment regimen.
Experimental: Double blind (DB) Group 2a: Golimumab 50mg SC & Placebo IV+MTX Participants, who do not achieve Disease Activity Score in 28 joints (DAS28) good response at Week 16, will be randomly assigned to receive golimumab 50 mg SC injection every 4 weeks + MTX from Week 16 to Week 48, along with placebo matched to golimumab intravenous infusion (IV) at Week 16, 20, 28, 36, and 44.	Drug: Golimumab 50 mg SC; Golimumab 50 milligram (mg) subcutaneous (SC) injection every 4 weeks.; Drug: Methotrexate (MTX); Participants will continue taking their current Methotrexate (MTX) treatment regimen.; Drug: Placebo IV; Placebo matched to golimumab intravenous infusion every 8 weeks.
Experimental: DB Group 2b: Golimumab 2mg/kg IV & Placebo SC + MTX Participants, who do not achieve DAS28 good response at Week 16, will be randomly assigned to receive golimumab 2 milligram per kilogram (mg/kg) intravenous infusion (IV) + MTX, at Week 16, 20, 28, 36 and 44, along with placebo matched to golimumab SC injection every 4 weeks from Week 16 to Week 48.	Drug: Golimumab 2 mg/kg IV; Golimumab 2 milligram per kilogram (mg/kg) intravenous infusion every 8 weeks.; Drug: Methotrexate (MTX); Participants will continue taking their current Methotrexate (MTX) treatment regimen.; Drug: Placebo SC; Placebo matched to golimumab SC injection every 4 weeks.
Experimental: OL Group 1: Golimumab 50 mg SC + MTX Participants, who achieve DAS28 good response at Week 16, will receive golimumab 50 mg SC injection every 4 weeks + MTX from Week 16 to Week 48.	Drug: Golimumab 50 mg SC; Golimumab 50 milligram (mg) subcutaneous (SC) injection every 4 weeks.; Drug: Methotrexate (MTX); Participants will continue taking their current Methotrexate (MTX) treatment regimen.
Experimental: OL Study Extension Group: Golimumab 50 mg SC + MTX Participants who complete the main study (Week 0 to Week 52), do not meet lack of efficacy criteria, and participate in the OL study extension, will receive golimumab 50 mg SC injection every 4 weeks + MTX from Week 52 to Week 72.	Drug: Golimumab 50 mg SC; Golimumab 50 milligram (mg) subcutaneous (SC) injection every 4 weeks.; Drug: Methotrexate (MTX); Participants will continue taking their current Methotrexate (MTX) treatment regimen.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Achieving Erythrocyte Sedimentation Rate (ESR)-Based American College of Rheumatology [ACR] 20 Response at Week 14 [Week 14]

   Erythrocyte Sedimentation Rate (ESR)-based ACR 20 response: greater than or equal to (>=) 20 percent (%) improvement from Baseline in tender (68 joints assessed) and swollen (66 joints assessed) joint counts and >=20% improvement from Baseline in 3 of the following 5 assessments: 1- Participant's assessment of pain using Visual Analog Scale (VAS) (0 to 10 centimeters [cm]), 2- Participant's global assessment of disease activity using VAS (0 to 10 cm), 3- Physician's global assessment of disease activity using VAS (0 to 10 cm), 4- Participant's assessment of physical function as measured by the Disability Index of the Health Assessment Questionnaire (HAQ-DI) (score of 0-3 in 8 functional areas), 5- ESR.

Secondary Outcome Measures

1. Percentage of Participants Who Achieved Erythrocyte Sedimentation Rate (ESR)-Based ACR20 Response at Week 2 [Within 2 weeks of initiating therapy]

   Erythrocyte Sedimentation Rate (ESR)-based ACR 20 response: greater than or equal to (>=) 20 percent (%) improvement from Baseline in tender (68 joints assessed) and swollen (66 joints assessed) joint counts and >=20% improvement from Baseline in 3 of the following 5 assessments: 1- Participant's assessment of pain using Visual Analog Scale (VAS) (0 to 10 centimeters [cm]), 2- Participant's global assessment of disease activity using VAS (0 to 10 cm), 3- Physician's global assessment of disease activity using VAS (0 to 10 cm), 4- Participant's assessment of physical function as measured by the Disability Index of the Health Assessment Questionnaire (HAQ-DI) (score of 0-3 in 8 functional areas), 5- ESR.

2. Percentage of Participants Who Achieved Erythrocyte Sedimentation Rate (ESR)-Based Disease Activity Score (DAS28) Response at Week 16 and Maintained Response Through Week 52 [Week 52]

   Erythrocyte Sedimentation Rate (ESR)-based disease activity score for 28-joints count (DAS28) as defined by European League Against Rheumatism (EULAR), response criteria was used to assess individual response as none, moderate, or good, depending on the extent of change from Baseline and the level of disease activity reached. A participant was classified as having achieved a DAS28 good response if, DAS28 was less than or equal to (<=) 3.2 at a given visit and improvement from Baseline was >1.2. Percentage of participants, who achieved ESR-based DAS 28 good response at Week 16 and maintained that response through Week 52, is reported.

3. Percentage of Participants Who Achieved Erythrocyte Sedimentation Rate (ESR)-Based ACR20 Response at Week 52 Relative to Week 16 [Week 52]

   Erythrocyte Sedimentation Rate (ESR)-based ACR 20 response: >=20 % improvement from Week 16 in tender (68 joints assessed) and swollen (66 joints assessed) joint counts and >=20% improvement from Week 16 in 3 of the following 5 assessments: 1- Participant's assessment of pain using VAS (0 to 10 cm), 2- Participant's global assessment of disease activity using VAS (0 to 10 cm), 3- Physician's global assessment of disease activity using VAS (0 to 10 cm), 4- Participant's assessment of physical function as measured by the Disability Index of the Health Assessment Questionnaire (HAQ-DI) (score of 0-3 in 8 functional areas), 5- ESR. Percentage of participants, who achieved ESR-based ACR 20 responses at Week 52 relative to Week 16, is reported.

4. Percentage of Participants Who Achieved ESR-based and C-Reactive Protein (CRP)-Based ACR20 Response at Week 76 Relative to Week 16 [Week 76]

   Erythrocyte Sedimentation Rate (ESR)-based/ C Reactive Protein (CRP)-based ACR 20 response: >=20 % improvement from Week 16 in tender (68 joints assessed) and swollen (66 joints assessed) joint counts and >=20% improvement from Week 16 in 3 of the following 5 assessments: 1- Participant's assessment of pain using VAS (0 to 10 cm), 2- Participant's global assessment of disease activity using VAS (0 to 10 cm), 3- Physician's global assessment of disease activity using VAS (0 to 10 cm), 4- Participant's assessment of physical function as measured by the Disability Index of the Health Assessment Questionnaire (HAQ-DI) (score of 0-3 in 8 functional areas), 5- ESR or CRP. Percentage of participants, who achieved ESR/ CRP-based ACR 20 responses at Week 76 relative to Week 16, is reported.

5. Change in ESR-based DAS28 Score at Week 76 Relative to Week 52 [Week 52, 76]

   Erythrocyte Sedimentation Rate (ESR)-based disease activity score for 28-joints count (DAS28) was calculated from number of swollen joint counts (SJC) and tender joint counts (TJC) using 28 joints count, ESR, and patient global assessment of disease activity (participant rated arthritis activity assessment with scores ranging 0 to 10; higher scores indicated greater disease activity). Total ESR-based DAS28 score range: 0 to 9.4, higher score=more disease activity.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have inadequate RA disease control prior to the first administration of study agent despite treatment with etanercept (Enbrel) + methotrexate or adalimumab (Humira) + methotrexate (MTX)

• Must have received a stable dose of MTX greater than or equal to (>=) 7.5 milligram (mg) per week to less than or equal to (<=) 25 mg per week for at least 4 consecutive weeks prior to the first screening visit and must plan to maintain that dose throughout the study

• Participants must have received etanercept or adalimumab in combination with MTX for a minimum of 3 months prior to the first visit

• Negative tuberculosis (TB) test

• Are capable of providing informed consent, which must be obtained prior to any study-related procedures

Exclusion Criteria:

• Have a history of latent or active granulomatous infection, including TB, histoplasmosis, or coccidioidomycosis, or are frequently in contact with individuals who carry active TB infection

• Have inflammatory diseases other than RA, including but not limited to psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus, primary Sjogren's or Lyme disease

• Have demonstrated a discernible improvement in disease activity between screening and prior to the first golimumab injection at Week 0

• Have any known malignancy or have a history of malignancy within the previous 5 years (with the exception of a nonmelanoma skin cancer that has been treated with no evidence of recurrence)

• Have a history of lymphoproliferative disease, including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease such as lymphadenopathy of unusual size or location

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States
2		Huntsville	Alabama	United States
3		Tuscaloosa	Alabama	United States
4		Mesa	Arizona	United States
5		Phoenix	Arizona	United States
6		Hot Springs	Arkansas	United States
7		Little Rock	Arkansas	United States
8		Covina	California	United States
9		Hemet	California	United States
10		Loma Linda	California	United States
11		Long Beach	California	United States
12		Murrieta	California	United States
13		Santa Maria	California	United States
14		Santa Monica	California	United States
15		Torrance	California	United States
16		Van Nuys	California	United States
17		Victorville	California	United States
18		Whittier	California	United States
19		Bridgeport	Connecticut	United States
20		Hamden	Connecticut	United States
21		Trumbull	Connecticut	United States
22		Aventura	Florida	United States
23		Fort Lauderdale	Florida	United States
24		Jacksonville	Florida	United States
25		Naples	Florida	United States
26		Orange Park	Florida	United States
27		Orlando	Florida	United States
28		Palm Harbor	Florida	United States
29		Plantation	Florida	United States
30		Sarasota	Florida	United States
31		Tampa	Florida	United States
32		Duluth	Georgia	United States
33		Coeur D'Alene	Idaho	United States
34		Idaho Falls	Idaho	United States
35		Rockford	Illinois	United States
36		South Bend	Indiana	United States
37		Bettendorf	Iowa	United States
38		Kansas City	Kansas	United States
39		Bowling Green	Kentucky	United States
40		Monroe	Louisiana	United States
41		New Orleans	Louisiana	United States
42		Wheaton	Maryland	United States
43		Rochester	Minnesota	United States
44		Flowood	Mississippi	United States
45		Tupelo	Mississippi	United States
46		Clayton	Missouri	United States
47		Florissant	Missouri	United States
48		Lincoln	Nebraska	United States
49		Freehold	New Jersey	United States
50		Brooklyn	New York	United States
51		Mineola	New York	United States
52		Plainview	New York	United States
53		Rochester	New York	United States
54		Smithtown	New York	United States
55		Charlotte	North Carolina	United States
56		Greenville	North Carolina	United States
57		Hickory	North Carolina	United States
58		Wilmington	North Carolina	United States
59		Akron	Ohio	United States
60		Columbus	Ohio	United States
61		Mayfield	Ohio	United States
62		Middleburg Heights	Ohio	United States
63		Edmond	Oklahoma	United States
64		Oklahoma City	Oklahoma	United States
65		Lake Oswego	Oregon	United States
66		Bethlehem	Pennsylvania	United States
67		Duncansville	Pennsylvania	United States
68		West Reading	Pennsylvania	United States
69		Wexford	Pennsylvania	United States
70		Charleston	South Carolina	United States
71		Columbia	South Carolina	United States
72		Myrtle Beach	South Carolina	United States
73		Hixson	Tennessee	United States
74		Jackson	Tennessee	United States
75		Kingsport	Tennessee	United States
76		Knoxville	Tennessee	United States
77		Nashville	Tennessee	United States
78		Austin	Texas	United States
79		Carrollton	Texas	United States
80		Dallas	Texas	United States
81		Houston	Texas	United States
82		San Antonio	Texas	United States
83		Arlington	Virginia	United States
84		Chesapeake	Virginia	United States
85		Seattle	Washington	United States
86		Spokane	Washington	United States
87		Beckley	West Virginia	United States
88		Clarksburg	West Virginia	United States
89		Glendale	Wisconsin	United States
90		Vienna		Austria
91		Brussel		Belgium
92		Genk		Belgium
93		Gent		Belgium
94		Liège		Belgium
95		Merksem		Belgium
96		Edmonton	Alberta	Canada
97		Kelowna	British Columbia	Canada
98		Vancouver	British Columbia	Canada
99		Winnipeg	Manitoba	Canada
100		Hamilton	Ontario	Canada
101		Montreal	Quebec	Canada
102		Quebec		Canada
103		St Johns		Canada
104		Hamburg		Germany
105		Herne		Germany
106		München		Germany
107		Ratingen		Germany
108		Heraklion- Crete		Greece
109		Thessalonikis		Greece
110		Stockholm		Sweden
111		Cannock		United Kingdom
112		Leeds		United Kingdom
113		London		United Kingdom
114		Manchester		United Kingdom
115		Merseyside		United Kingdom
116		Newcastle Upon Tyne		United Kingdom
117		Wigan		United Kingdom

Sponsors and Collaborators

• Janssen Biotech, Inc.
• Merck Sharp & Dohme LLC

Investigators

• Study Director: Janssen Biotech, Inc. Clinical Trial, Janssen Biotech, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen Biotech, Inc.
• ClinicalTrials.gov Identifier: NCT01004432
• Other Study ID Numbers: CR016663; CNTO148ART3002; 2009-010582-23; GO SAVE
• First Posted: Oct 30, 2009
• Last Update Posted: Apr 30, 2015
• Last Verified: Apr 1, 2015

• Keywords provided by Janssen Biotech, Inc.: humira, remicade; rheumatoid arthritis; enbrel failure; humira failure; arthritis; enbrel
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Autoimmune Diseases; Golimumab; Methotrexate; Antibodies, Monoclonal

Study Results

Participant Flow

Arm/Group Title	Open-label (OL) Overall Group: Golimumab 50 mg SC + MTX	OL Group 1: Golimumab 50 mg SC + MTX	Double Blind (DB) Group 2a: Golimumab 50mg SC & Placebo IV+MTX	DB Group 2b: Golimumab 2mg/kg IV & Placebo SC + MTX	OL Study Extension Group: Golimumab 50 mg SC + MTX
Arm/Group Description	All enrolled and dosed participants received golimumab 50 mg SC injection every 4 weeks + MTX from Week 0 to Week 12.	Participants, who achieved Disease Activity Score in 28 joints (DAS28) good response at Week 16, received Golimumab 50 milligram (mg) subcutaneous (SC) injection every 4 weeks + Methotrexate (MTX) from Week 16 to Week 48.	Participants, who did not achieve DAS28 good response at Week 16, were randomly assigned to receive golimumab 50 mg SC injection every 4 weeks + MTX from Week 16 to Week 48, along with placebo matched to golimumab intravenous infusion (IV) at Week 16, 20, 28, 36, and 44.	Participants, who did not achieve DAS28 good response at Week 16, were randomly assigned to receive golimumab 2 milligram per kilogram (mg/kg) intravenous infusion (IV) + MTX, at Week 16, 20, 28, 36 and 44, along with placebo matched to golimumab SC injection every 4 weeks from Week 16 to Week 48.	Participants who completed the main study (Week 0 to Week 52), not met lack of efficacy criteria, and participated in the OL study extension, received golimumab 50 mg SC injection every 4 weeks + MTX from Week 52 to Week 72.
Period Title: Open-label (OL) Period (Week 0 - 16)
STARTED	433	0	0	0	0
COMPLETED	350	0	0	0	0
NOT COMPLETED	83	0	0	0	0
Period Title: Open-label (OL) Period (Week 0 - 16)
STARTED	0	75	91	184	0
COMPLETED	0	65	54	126	0
NOT COMPLETED	0	10	37	58	0
Period Title: Open-label (OL) Period (Week 0 - 16)
STARTED	0	0	0	0	212
COMPLETED	0	0	0	0	194
NOT COMPLETED	0	0	0	0	18

Baseline Characteristics

Arm/Group Title	OL Overall Group: Golimumab 50 mg SC + MTX
Arm/Group Description	All enrolled and dosed participants received golimumab 50 mg SC injection every 4 weeks + MTX from Week 0 to Week 12.
Overall Participants	433
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.7 (11.52)
Sex: Female, Male (Count of Participants)
Female	358 82.7%
Male	75 17.3%
Region of Enrollment (participants) [Number]
Austria	1 0.2%
Belgium	9 2.1%
Canada	37 8.5%
Germany	7 1.6%
Greece	8 1.8%
Italy	12 2.8%
Sweden	1 0.2%
United Kingdom	9 2.1%
United States	349 80.6%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving Erythrocyte Sedimentation Rate (ESR)-Based American College of Rheumatology [ACR] 20 Response at Week 14
Description	Erythrocyte Sedimentation Rate (ESR)-based ACR 20 response: greater than or equal to (>=) 20 percent (%) improvement from Baseline in tender (68 joints assessed) and swollen (66 joints assessed) joint counts and >=20% improvement from Baseline in 3 of the following 5 assessments: 1- Participant's assessment of pain using Visual Analog Scale (VAS) (0 to 10 centimeters [cm]), 2- Participant's global assessment of disease activity using VAS (0 to 10 cm), 3- Physician's global assessment of disease activity using VAS (0 to 10 cm), 4- Participant's assessment of physical function as measured by the Disability Index of the Health Assessment Questionnaire (HAQ-DI) (score of 0-3 in 8 functional areas), 5- ESR.
Time Frame	Week 14

Outcome Measure Data

Analysis Population Description

Modified Intent To Treat (mITT) population included all enrolled participants who had Week 0 measurements and received at least 1 dose of study drug.

Arm/Group Title	OL Overall Group: Golimumab 50 mg SC + MTX
Arm/Group Description	All enrolled and dosed participants received golimumab 50 mg SC injection every 4 weeks + MTX from Week 0 to Week 12.
Measure Participants	433
Number (95% Confidence Interval) [percentage of participants]	34.9 8.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OL Overall Group: Golimumab 50 mg SC + MTX
	Comments	null hypothesis: proportion <=0.2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	One sided test adjusting for conducting one interim analysis
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Percentage achive ACR 20 response
	Estimated Value	34.9
	Confidence Interval	(2-Sided) 95%; 30.4 to 39.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants Who Achieved Erythrocyte Sedimentation Rate (ESR)-Based ACR20 Response at Week 2
Description	Erythrocyte Sedimentation Rate (ESR)-based ACR 20 response: greater than or equal to (>=) 20 percent (%) improvement from Baseline in tender (68 joints assessed) and swollen (66 joints assessed) joint counts and >=20% improvement from Baseline in 3 of the following 5 assessments: 1- Participant's assessment of pain using Visual Analog Scale (VAS) (0 to 10 centimeters [cm]), 2- Participant's global assessment of disease activity using VAS (0 to 10 cm), 3- Physician's global assessment of disease activity using VAS (0 to 10 cm), 4- Participant's assessment of physical function as measured by the Disability Index of the Health Assessment Questionnaire (HAQ-DI) (score of 0-3 in 8 functional areas), 5- ESR.
Time Frame	Within 2 weeks of initiating therapy

Outcome Measure Data

Analysis Population Description

Modified Intent To Treat (mITT) population included all enrolled participants who had Week 0 measurements and received at least 1 dose of study drug.

Arm/Group Title	OL Overall Group: Golimumab 50 mg SC + MTX
Arm/Group Description	All enrolled and dosed participants received golimumab 50 mg SC injection every 4 weeks + MTX from Week 0 to Week 12.
Measure Participants	433
Number (95% Confidence Interval) [percentage of participants]	24.5 5.7%

3. Secondary Outcome

Title	Percentage of Participants Who Achieved Erythrocyte Sedimentation Rate (ESR)-Based Disease Activity Score (DAS28) Response at Week 16 and Maintained Response Through Week 52
Description	Erythrocyte Sedimentation Rate (ESR)-based disease activity score for 28-joints count (DAS28) as defined by European League Against Rheumatism (EULAR), response criteria was used to assess individual response as none, moderate, or good, depending on the extent of change from Baseline and the level of disease activity reached. A participant was classified as having achieved a DAS28 good response if, DAS28 was less than or equal to (<=) 3.2 at a given visit and improvement from Baseline was >1.2. Percentage of participants, who achieved ESR-based DAS 28 good response at Week 16 and maintained that response through Week 52, is reported.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Open-label modified Intent To Treat (mITT) population included all participants, who received at least 1 open-label golimumab 50 mg SC injection during the continued open-label/ double-blind treatment period.

Arm/Group Title	OL Group 1: Golimumab 50 mg SC + MTX
Arm/Group Description	Participants, who achieved Disease Activity Score in 28 joints (DAS28) good response at Week 16, received Golimumab 50 milligram (mg) subcutaneous (SC) injection every 4 weeks + Methotrexate (MTX) from Week 16 to Week 48.
Measure Participants	75
Number (95% Confidence Interval) [percentage of participants]	22.7 5.2%

4. Secondary Outcome

Title	Percentage of Participants Who Achieved Erythrocyte Sedimentation Rate (ESR)-Based ACR20 Response at Week 52 Relative to Week 16
Description	Erythrocyte Sedimentation Rate (ESR)-based ACR 20 response: >=20 % improvement from Week 16 in tender (68 joints assessed) and swollen (66 joints assessed) joint counts and >=20% improvement from Week 16 in 3 of the following 5 assessments: 1- Participant's assessment of pain using VAS (0 to 10 cm), 2- Participant's global assessment of disease activity using VAS (0 to 10 cm), 3- Physician's global assessment of disease activity using VAS (0 to 10 cm), 4- Participant's assessment of physical function as measured by the Disability Index of the Health Assessment Questionnaire (HAQ-DI) (score of 0-3 in 8 functional areas), 5- ESR. Percentage of participants, who achieved ESR-based ACR 20 responses at Week 52 relative to Week 16, is reported.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Double-blind modified Intent To Treat (mITT) population included participants who were randomized at Week 16 to SC or IV golimumab (Groups 2a and 2b) and received at least 1 dose of study drug after randomization.

Arm/Group Title	DB Group 2a: Golimumab 50 mg SC & Placebo IV + MTX	DB Group 2b: Golimumab 2 mg/kg IV & Placebo SC + MTX
Arm/Group Description	Participants, who did not achieved DAS28 good response at Week 16, were randomly assigned to receive golimumab 50 mg SC injection every 4 weeks + MTX from Week 16 to Week 48, along with placebo matched to golimumab intravenous infusion (IV) at Week 16, 20, 28, 36, and 44.	Participants, who did not achieve DAS28 good response at Week 16, were randomly assigned to receive golimumab 2 milligram per kilogram (mg/kg) intravenous infusion (IV) + MTX, at Week 16, 20, 28, 36 and 44, along with placebo matched to golimumab SC injection every 4 weeks from Week 16 to Week 48.
Measure Participants	91	184
Number (95% Confidence Interval) [percentage of participants]	13.2 3%	9.2 NaN

5. Secondary Outcome

Title	Percentage of Participants Who Achieved ESR-based and C-Reactive Protein (CRP)-Based ACR20 Response at Week 76 Relative to Week 16
Description	Erythrocyte Sedimentation Rate (ESR)-based/ C Reactive Protein (CRP)-based ACR 20 response: >=20 % improvement from Week 16 in tender (68 joints assessed) and swollen (66 joints assessed) joint counts and >=20% improvement from Week 16 in 3 of the following 5 assessments: 1- Participant's assessment of pain using VAS (0 to 10 cm), 2- Participant's global assessment of disease activity using VAS (0 to 10 cm), 3- Physician's global assessment of disease activity using VAS (0 to 10 cm), 4- Participant's assessment of physical function as measured by the Disability Index of the Health Assessment Questionnaire (HAQ-DI) (score of 0-3 in 8 functional areas), 5- ESR or CRP. Percentage of participants, who achieved ESR/ CRP-based ACR 20 responses at Week 76 relative to Week 16, is reported.
Time Frame	Week 76

Outcome Measure Data

Analysis Population Description

Study extension mITT population included all participants, who were enrolled into the 24-week study extension period at Week 52, and received at least 1 golimumab SC injection during the study extension period. Participants reported in other groups are subgroups of 'Study Extension OL Group' by treatment received in the OL/DB phase (Weeks 16-52).

Arm/Group Title	OL Group 1: Golimumab 50 mg SC + MTX	DB Group 2a: Golimumab 50 mg SC & Placebo IV + MTX	DB Group 2b: Golimumab 2 mg/kg IV & Placebo SC + MTX	OL Study Extension Group: Golimumab 50 mg SC + MTX
Arm/Group Description	Participants, who achieved Disease Activity Score in 28 joints (DAS28) good response at Week 16, received Golimumab 50 milligram (mg) subcutaneous (SC) injection every 4 weeks + Methotrexate (MTX) from Week 16 to Week 48.	Participants, who did not achieved DAS28 good response at Week 16, were randomly assigned to receive golimumab 50 mg SC injection every 4 weeks + MTX from Week 16 to Week 48, along with placebo matched to golimumab intravenous infusion (IV) at Week 16, 20, 28, 36, and 44.	Participants, who did not achieve DAS28 good response at Week 16, were randomly assigned to receive golimumab 2 milligram per kilogram (mg/kg) intravenous infusion (IV) + MTX, at Week 16, 20, 28, 36 and 44, along with placebo matched to golimumab SC injection every 4 weeks from Week 16 to Week 48.	Participants who completed the main study (Week 0 to Week 52), not met lack of efficacy criteria, and participated in the OL study extension, received golimumab 50 mg SC injection every 4 weeks + MTX from Week 52 to Week 72.
Measure Participants	63	47	102	212
ESR-based ACR 20 Response	7.9 1.8%	8.5 NaN	15.7 NaN	11.8 NaN
CRP-based ACR 20 Response	7.9 1.8%	8.5 NaN	17.6 NaN	12.7 NaN

6. Secondary Outcome

Title	Change in ESR-based DAS28 Score at Week 76 Relative to Week 52
Description	Erythrocyte Sedimentation Rate (ESR)-based disease activity score for 28-joints count (DAS28) was calculated from number of swollen joint counts (SJC) and tender joint counts (TJC) using 28 joints count, ESR, and patient global assessment of disease activity (participant rated arthritis activity assessment with scores ranging 0 to 10; higher scores indicated greater disease activity). Total ESR-based DAS28 score range: 0 to 9.4, higher score=more disease activity.
Time Frame	Week 52, 76

Outcome Measure Data

Analysis Population Description

Study extension mITT population. Here 'N' (number of participants analyzed) = participants evaluable for this measure and 'n' = participants evaluable at specified time point for each arm, respectively. Participants reported in other groups are subgroups of 'Study Extension OL Group' by treatment received in the OL/DB phase (Weeks 16-52).

Arm/Group Title	OL Group 1: Golimumab 50 mg SC + MTX	DB Group 2a: Golimumab 50 mg SC & Placebo IV + MTX	DB Group 2b: Golimumab 2 mg/kg IV & Placebo SC + MTX	OL Study Extension Group: Golimumab 50 mg SC + MTX
Arm/Group Description	Participants, who achieved Disease Activity Score in 28 joints (DAS28) good response at Week 16, received Golimumab 50 milligram (mg) subcutaneous (SC) injection every 4 weeks + Methotrexate (MTX) from Week 16 to Week 48.	Participants, who did not achieved DAS28 good response at Week 16, were randomly assigned to receive golimumab 50 mg SC injection every 4 weeks + MTX from Week 16 to Week 48, along with placebo matched to golimumab intravenous infusion (IV) at Week 16, 20, 28, 36, and 44.	Participants, who did not achieve DAS28 good response at Week 16, were randomly assigned to receive golimumab 2 milligram per kilogram (mg/kg) intravenous infusion (IV) + MTX, at Week 16, 20, 28, 36 and 44, along with placebo matched to golimumab SC injection every 4 weeks from Week 16 to Week 48.	Participants who completed the main study (Week 0 to Week 52), not met lack of efficacy criteria, and participated in the OL study extension, received golimumab 50 mg SC injection every 4 weeks + MTX from Week 52 to Week 72.
Measure Participants	61	40	95	196
Week 52 (n = 61, 40, 95, 196)	3.182 (1.1109)	4.070 (0.8037)	4.394 (1.2389)	3.950 (1.2379)
Change at Week 76 (n = 57, 33, 84, 174)	-0.136 (1.2095)	0.209 (1.2253)	-0.017 (1.0518)	-0.013 (1.1386)

Adverse Events

Arm/Group Title	OL Overall Group: Golimumab 50 mg SC + MTX		OL Group 1: Golimumab 50 mg SC + MTX		Double Blind (DB) Group 2a: Golimumab 50mg SC & Placebo IV+MTX		DB Group 2b: Golimumab 2mg/kg IV & Placebo SC + MTX		OL Study Extension Group: Golimumab 50 mg SC + MTX
Arm/Group Description	All enrolled and dosed participants received golimumab 50 mg SC injection every 4 weeks + MTX from Week 0 to Week 12.		Participants, who achieved Disease Activity Score in 28 joints (DAS28) good response at Week 16, received Golimumab 50 milligram (mg) subcutaneous (SC) injection every 4 weeks + Methotrexate (MTX) from Week 16 to Week 48.		Participants, who did not achieve DAS28 good response at Week 16, were randomly assigned to receive golimumab 50 mg SC injection every 4 weeks + MTX from Week 16 to Week 48, along with placebo matched to golimumab intravenous infusion (IV) at Week 16, 20, 28, 36, and 44.		Participants, who did not achieve DAS28 good response at Week 16, were randomly assigned to receive golimumab 2 milligram per kilogram (mg/kg) intravenous infusion (IV) + MTX, at Week 16, 20, 28, 36 and 44, along with placebo matched to golimumab SC injection every 4 weeks from Week 16 to Week 48.		Participants who completed the main study (Week 0 to Week 52), not met lack of efficacy criteria, and participated in the OL study extension, received golimumab 50 mg SC injection every 4 weeks + MTX from Week 52 to Week 72.
All Cause Mortality
	OL Overall Group: Golimumab 50 mg SC + MTX		OL Group 1: Golimumab 50 mg SC + MTX		Double Blind (DB) Group 2a: Golimumab 50mg SC & Placebo IV+MTX		DB Group 2b: Golimumab 2mg/kg IV & Placebo SC + MTX		OL Study Extension Group: Golimumab 50 mg SC + MTX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	OL Overall Group: Golimumab 50 mg SC + MTX		OL Group 1: Golimumab 50 mg SC + MTX		Double Blind (DB) Group 2a: Golimumab 50mg SC & Placebo IV+MTX		DB Group 2b: Golimumab 2mg/kg IV & Placebo SC + MTX		OL Study Extension Group: Golimumab 50 mg SC + MTX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/433 (4.6%)		2/75 (2.7%)		4/91 (4.4%)		10/184 (5.4%)		10/212 (4.7%)
Cardiac disorders
Bradycardia	0/433 (0%)		0/75 (0%)		0/91 (0%)		1/184 (0.5%)		0/212 (0%)
Cardiac failure congestive	0/433 (0%)		0/75 (0%)		0/91 (0%)		1/184 (0.5%)		0/212 (0%)
Coronary artery disease	0/433 (0%)		0/75 (0%)		0/91 (0%)		1/184 (0.5%)		1/212 (0.5%)
Acute myocardial infarction	0/433 (0%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		1/212 (0.5%)
Gastrointestinal disorders
Oesophagitis haemorrhagic	0/433 (0%)		0/75 (0%)		1/91 (1.1%)		0/184 (0%)		0/212 (0%)
Small intestinal obstruction	0/433 (0%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		1/212 (0.5%)
Upper gastrointestinal haemorrhage	0/433 (0%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		1/212 (0.5%)
General disorders
Chest pain	1/433 (0.2%)		0/75 (0%)		0/91 (0%)		3/184 (1.6%)		1/212 (0.5%)
Pyrexia	0/433 (0%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		1/212 (0.5%)
Infections and infestations
Appendicitis	1/433 (0.2%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		0/212 (0%)
Cellulitis	1/433 (0.2%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		1/212 (0.5%)
Diverticulitis	1/433 (0.2%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		0/212 (0%)
Gastroenteritis	1/433 (0.2%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		0/212 (0%)
Gastroenteritis viral	1/433 (0.2%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		0/212 (0%)
Pneumonia	1/433 (0.2%)		0/75 (0%)		1/91 (1.1%)		2/184 (1.1%)		0/212 (0%)
Sepsis	0/433 (0%)		0/75 (0%)		0/91 (0%)		1/184 (0.5%)		0/212 (0%)
Urinary tract infection	0/433 (0%)		0/75 (0%)		0/91 (0%)		1/184 (0.5%)		0/212 (0%)
Urosepsis	1/433 (0.2%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		0/212 (0%)
Wound infection staphylococcal	1/433 (0.2%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		0/212 (0%)
Hepatitis C	0/433 (0%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		1/212 (0.5%)
Injury, poisoning and procedural complications
Fall	1/433 (0.2%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		0/212 (0%)
Intentional overdose	0/433 (0%)		1/75 (1.3%)		0/91 (0%)		0/184 (0%)		0/212 (0%)
Upper limb fracture	1/433 (0.2%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		0/212 (0%)
Femur fracture	0/433 (0%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		1/212 (0.5%)
Metabolism and nutrition disorders
Diabetic ketoacidosis	1/433 (0.2%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		0/212 (0%)
Dehydration	0/433 (0%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		1/212 (0.5%)
Hypokalaemia	0/433 (0%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		1/212 (0.5%)
Musculoskeletal and connective tissue disorders
Back pain	2/433 (0.5%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		0/212 (0%)
Joint effusion	1/433 (0.2%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		0/212 (0%)
Muscular weakness	0/433 (0%)		1/75 (1.3%)		0/91 (0%)		0/184 (0%)		0/212 (0%)
Osteoarthritis	1/433 (0.2%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		1/212 (0.5%)
Pain in extremity	0/433 (0%)		1/75 (1.3%)		0/91 (0%)		0/184 (0%)		0/212 (0%)
Polymyalgia rheumatica	1/433 (0.2%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		0/212 (0%)
Tenosynovitis	0/433 (0%)		0/75 (0%)		1/91 (1.1%)		0/184 (0%)		0/212 (0%)
Arthralgia	0/433 (0%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		1/212 (0.5%)
Rheumatoid arthritis	1/433 (0.2%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		0/212 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	0/433 (0%)		0/75 (0%)		0/91 (0%)		1/184 (0.5%)		0/212 (0%)
Breast cancer stage III	0/433 (0%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		1/212 (0.5%)
Essential thrombocythaemia	0/433 (0%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		1/212 (0.5%)
Nervous system disorders
Carotid artery occlusion	0/433 (0%)		0/75 (0%)		0/91 (0%)		1/184 (0.5%)		0/212 (0%)
Cerebral haemorrhage	1/433 (0.2%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		0/212 (0%)
Intracranial aneurysm	0/433 (0%)		0/75 (0%)		0/91 (0%)		1/184 (0.5%)		0/212 (0%)
Polyneuropathy	1/433 (0.2%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		0/212 (0%)
Renal and urinary disorders
Renal failure acute	1/433 (0.2%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		1/212 (0.5%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/433 (0%)		0/75 (0%)		0/91 (0%)		1/184 (0.5%)		0/212 (0%)
Asthma	2/433 (0.5%)		0/75 (0%)		1/91 (1.1%)		1/184 (0.5%)		0/212 (0%)
Emphysema	1/433 (0.2%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		0/212 (0%)
Pulmonary embolism	0/433 (0%)		0/75 (0%)		1/91 (1.1%)		0/184 (0%)		1/212 (0.5%)
Respiratory distress	1/433 (0.2%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		0/212 (0%)
Pneumothorax	0/433 (0%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		1/212 (0.5%)
Vascular disorders
Deep vein thrombosis	1/433 (0.2%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		0/212 (0%)
Hypotension	0/433 (0%)		0/75 (0%)		0/91 (0%)		0/184 (0%)		1/212 (0.5%)
Other (Not Including Serious) Adverse Events
	OL Overall Group: Golimumab 50 mg SC + MTX		OL Group 1: Golimumab 50 mg SC + MTX		Double Blind (DB) Group 2a: Golimumab 50mg SC & Placebo IV+MTX		DB Group 2b: Golimumab 2mg/kg IV & Placebo SC + MTX		OL Study Extension Group: Golimumab 50 mg SC + MTX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	123/433 (28.4%)		21/75 (28%)		30/91 (33%)		54/184 (29.3%)		61/212 (28.8%)
Infections and infestations
Bronchitis	12/433 (2.8%)		2/75 (2.7%)		6/91 (6.6%)		11/184 (6%)		4/212 (1.9%)
Sinusitis	17/433 (3.9%)		4/75 (5.3%)		4/91 (4.4%)		13/184 (7.1%)		12/212 (5.7%)
Upper respiratory tract infection	29/433 (6.7%)		7/75 (9.3%)		5/91 (5.5%)		15/184 (8.2%)		13/212 (6.1%)
Urinary tract infection	24/433 (5.5%)		3/75 (4%)		2/91 (2.2%)		11/184 (6%)		13/212 (6.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	20/433 (4.6%)		2/75 (2.7%)		8/91 (8.8%)		8/184 (4.3%)		11/212 (5.2%)
Rheumatoid arthritis	13/433 (3%)		2/75 (2.7%)		9/91 (9.9%)		9/184 (4.9%)		11/212 (5.2%)
Nervous system disorders
Headache	24/433 (5.5%)		0/75 (0%)		1/91 (1.1%)		5/184 (2.7%)		3/212 (1.4%)
Psychiatric disorders
Depression	7/433 (1.6%)		4/75 (5.3%)		3/91 (3.3%)		2/184 (1.1%)		5/212 (2.4%)

Limitations/Caveats

Since participants assigned to the double blind groups were non-responders to at least 2 anti-Tumor Necrosis Factors (TNF), thus comprising a very difficult group to treat.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.