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)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 433
- 主要终点
- Percentage of Participants Achieving Erythrocyte Sedimentation Rate (ESR)-Based American College of Rheumatology [ACR] 20 Response at Week 14
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Methotrexate (MTX) (Drug)
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.
干预措施: Golimumab 50 mg SC (Drug)
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.
干预措施: Golimumab 50 mg SC (Drug)
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.
干预措施: Methotrexate (MTX) (Drug)
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.
干预措施: Placebo IV (Drug)
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.
干预措施: Golimumab 2 mg/kg IV (Drug)
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.
干预措施: Methotrexate (MTX) (Drug)
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.
干预措施: Placebo SC (Drug)
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.
干预措施: Golimumab 50 mg SC (Drug)
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.
干预措施: Methotrexate (MTX) (Drug)
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.
干预措施: Golimumab 50 mg SC (Drug)
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.
干预措施: Methotrexate (MTX) (Drug)
结局指标
主要结局
Percentage of Participants Achieving Erythrocyte Sedimentation Rate (ESR)-Based American College of Rheumatology [ACR] 20 Response at Week 14
时间窗: 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.
次要结局
- Percentage of Participants Who Achieved Erythrocyte Sedimentation Rate (ESR)-Based ACR20 Response at Week 2(Within 2 weeks of initiating therapy)
- Change in ESR-based DAS28 Score at Week 76 Relative to Week 52(Week 52, 76)
- 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)
- Percentage of Participants Who Achieved Erythrocyte Sedimentation Rate (ESR)-Based ACR20 Response at Week 52 Relative to Week 16(Week 52)
- Percentage of Participants Who Achieved ESR-based and C-Reactive Protein (CRP)-Based ACR20 Response at Week 76 Relative to Week 16(Week 76)