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

Phase 3

Completed

• Conditions: Arthritis; Arthritis, Rheumatoid; Autoimmune Diseases
• Interventions: Drug: Golimumab 50 mg SC; Drug: Golimumab 2 mg/kg IV; Drug: Methotrexate (MTX); Drug: Placebo SC; Drug: Placebo IV

• Registration Number: NCT01004432
• Lead Sponsor: Janssen Biotech, Inc.

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.

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 Timeline

• Study First Submitted: 2009-10-29
• Study First Submitted QC: 2009-10-29
• Study First Posted: 2009-10-30
• Study Start: 2009-12
• Primary Completion: 2013-07
• Study Completion: 2013-10
• Results First Submitted: 2014-03-13
• Results First Submitted QC: 2014-04-14
• Results First Posted: 2014-05-13
• Status Verified: 2015-04
• Last Update Submitted: 2015-04-09
• Last Update Posted: 2015-04-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 433

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Open-label (OL) Overall Group: Golimumab 50 mg SC + MTX	Golimumab 50 mg SC	All enrolled and dosed participants receive golimumab 50 milligram (mg) subcutaneous (SC) injection every 4 weeks + Methotrexate (MTX) from Week 0 to Week 12.
Double blind (DB) Group 2a: Golimumab 50mg SC & Placebo IV+MTX	Golimumab 50 mg SC	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.
Double blind (DB) Group 2a: Golimumab 50mg SC & Placebo IV+MTX	Methotrexate (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.
DB Group 2b: Golimumab 2mg/kg IV & Placebo SC + MTX	Golimumab 2 mg/kg IV	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.
OL Group 1: Golimumab 50 mg SC + MTX	Golimumab 50 mg SC	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.
OL Group 1: Golimumab 50 mg SC + MTX	Methotrexate (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.
OL Study Extension Group: Golimumab 50 mg SC + MTX	Golimumab 50 mg SC	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.
OL Study Extension Group: Golimumab 50 mg SC + MTX	Methotrexate (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.
DB Group 2b: Golimumab 2mg/kg IV & Placebo SC + MTX	Methotrexate (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.
Open-label (OL) Overall Group: Golimumab 50 mg SC + MTX	Methotrexate (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.
DB Group 2b: Golimumab 2mg/kg IV & Placebo SC + MTX	Placebo SC	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.
Double blind (DB) Group 2a: Golimumab 50mg SC & Placebo IV+MTX	Placebo IV	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
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.
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.
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.
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.