A Golimumab Phase 3b, Multicenter, Assessment of Intravenous Efficacy in Rheumatoid Arthritis Subjects Who Have Diminished Disease Control Despite Treatment With Infliximab (REMICADE®)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 7
- 试验地点
- 53
- 主要终点
- Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20) Response at Week 24
研究概览
简要总结
This is a Phase 3b, multicenter study of the efficacy of golimumab 2 mg/kg IV in subjects with active rheumatoid arthritis who are receiving methotrexate and have inadequate disease control (defined as an erythrocyte sedimentation rate [ESR]-based Disease Activity Score in 28 joints [DAS28] ≥ 3.2 and ≥ 4 swollen and ≥ 4 tender joints) despite current anti-TNFα therapy with infliximab 2 - 4 mg/kg every 4 weeks, 2 - 5 mg/kg every 5 weeks, 3 - 6 mg/kg every 6 weeks, 3 - 7mg/kg every 7 weeks, or 4 - 8 mg/kg every 8 weeks.
To be eligible for participation, subjects must have previously demonstrated initial and/or temporary improvement in disease signs and symptoms, who have since exhibited a diminished response despite continued treatment. It is estimated that 200 subjects will be enrolled in the study at approximately 85 global sites.
详细描述
The study employs an open-label "active switch" design that moves subjects from infliximab to golimumab 2 mg/kg IV. In general, subjects eligible for the study include men or women who are currently receiving infliximab in actual clinical practice who are at least 18 years of age with active rheumatoid arthritis, and have previously demonstrated initial and/or temporary improvement in disease signs and symptoms, but now exhibit a diminished response and inadequate disease control despite continued treatment. Subjects must have received infliximab in combination with methotrexate for a minimum of 9 months prior to the first screening visit.
The screening visit will occur sometime between Week -12 and Week -10. Consenting subjects who meet screening criteria will receive their final dose of infliximab at Week -8 as part of actual clinical practice. Golimumab IV treatment, which will be supplied by the sponsor, will be received at Weeks 0, 4, 12, 20, and 28. The primary endpoint is at Week 24, the final efficacy assessment is at Week 32, and a follow-up safety assessment by telephone is at Week 44. There will be a maximum of 36 weeks between the last infliximab infusion at Week -8 and the last infusion of golimumab at Week 28. The duration of study participation is expected to be a maximum of 56 weeks (including the Screening Period, 32 weeks of golimumab treatment and assessment, and a 12-week safety follow-up).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 76 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Major Inclusion Criteria include (but not limited to):
- •Have a diagnosis of Rheumatoid Arthritis (according to the revised 1987 criteria of the American Rheumatism Association).
- •Treatment with infliximab and methotrexate for >= 9 months, (with stable doses of methotrexate over last 16 weeks of 7.5 mg/week to 25 mg/week) and (anti-TNFα therapy with infliximab 2 - 4 mg/kg every 4 weeks, 2 - 5 mg/kg every 5 weeks, 3 - 6 mg/kg every 6 weeks, 3 - 7mg/kg every 7 weeks, or 4 - 8 mg/kg every 8 weeks).
- •Disease Activity Score 28 (DAS28) ≥ 3.2 based on Erythrocyte Sedimentation Rate (ESR) at Week -8 and Week
- •Swollen joint count (SJC) ≥ 4 and tender joint count (TJC) ≥ 4 at Week - 8 and at Week
- •Prior response confirmed by physician.
排除标准
- •include (but not limited to):
- •Have a history of latent or active granulomatous infection, including histoplasmosis, or Have a history of latent or active granulomatous infection, including histoplasmosis, or coccidioidomycosis, prior to the first screening visit or during the Screening Period.
- •Have had a Bacille Calmette-Guérin (BCG) vaccination within 12 months of screening.
- •Have a chest radiograph within 3 months prior to the first administration of study agent that shows an abnormality suggestive of a malignancy or current active infection, including tuberculosis (TB), histoplasmosis, or coccidioidomycosis.
- •Have previously received more than 1 of the currently approved subcutaneous (SC) administered anti-TNFα agents, etanercept, certolizumab pegol, golimumab, or adalimumab.
- •Are pregnant, nursing, or planning a pregnancy or fathering a child within 6 months after receiving the last administration of the study agent.
- •Weight less than 35 kg or greater than 110 kg (less than 77 pounds or greater than 242 pounds).
研究组 & 干预措施
Golimumab 2 mg/kg IV
Study drug (golimumab 2 mg/kg IV) will be administered as an intravenous (IV) infusion at Weeks 0, 4, 12, 20 and 28.
干预措施: Golimumab 2 mg/kg IV (Biological)
结局指标
主要结局
Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20) Response at Week 24
时间窗: Week 24
The ACR 20 Response is defined as greater than or equal to (\>=) 20 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and \>=20 percent improvement in 3 of following 5 assessments: patient's assessment of pain using Visual Analog Scale (VAS; 0-10 millimeter \[mm\], 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, \[0 mm=no pain to 100 mm=worst possible pain\]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas. The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and erythrocyte sedimentation rate (ESR).
次要结局
- Percentage of Participants Who Achieved an ACR 20 Response at Week 24 With Confirmed Presence of Antibodies to Infliximab(Week 24)
- Percentage of Participants Who Acheived ACR 20 Response at Week 24 With Trough Infliximab Levels Below the Lower Limit of Quantification (LLOQ)(Week 24)