A Randomized, Double-blind, Parallel-group Phase III Study to Demonstrate Equivalent Efficacy and to Compare Safety & Immunogenicity of GP2015 and Enbrel® (EU Authorized) in Patients With Moderate to Severe, Active Rheumatoid Arthritis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Sandoz
- 入组人数
- 376
- 试验地点
- 1
- 主要终点
- Safety: Change in DAS28-CRP Score From Baseline to Week 24 in Patients Treated With GP2015 and Patients Treated With Enbrel
研究概览
简要总结
Demonstrate equivalent efficacy of GP2015 and EU-authorized Enbrel in patients with moderate to severe, active (RA) who had an inadequate response to disease modifying anti-rheumatic drugs (DMARD) including methotrexate (MTX).
详细描述
Demonstrate equivalent efficacy of GP2015 and EU-authorized Enbrel in patients with moderate to severe, active (RA) who had an inadequate response to disease modifying anti-rheumatic drugs (DMARD) including methotrexate (MTX). In addition, data on the safety profiles of both products, including immunogenicity and local tolerability at the injection sites, will be collected and compared.
An additional study objective is to identify any potential risk of the transition from Enbrel to GP2015 in terms of general safety and immunogenicity in RA patients
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
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
- •Patients at least 18 years of age with RA diagnosis according to ACR 1987 or ACR/EULAR 20110 criteria >/= 6 months at the time of baseline visit
- •Patient must have active disease defined as DAS28-CRP>/=3.2
- •Patients must have CRP level above ULN >5mg/l) or erythrocyte sedimentation rate (ESR) >/=28mm/h
- •Patients must have inadequate clinical response to MTX at a dose of 10-25 mg/wk after proper dose escalation according to local standards
排除标准
- •Previous exposure to etanercept in the past
- •Patients with functional status class IV according to the ACR 1991 revised criteria
- •History of active tuberculosis (TB) or Presence of latent (inactive)TB detected by imaging and/or by the QuantiFERON-TB Gold test at screening
研究组 & 干预措施
50mg GP2015
Group 1 will receive treatment with 50mg GP2015 by subcutaneous injection every week up to 24 weeks (Treatment Period 1) after which patients achieving at least a moderate clinical response continue treatment with 50mg GP2015 subcutaneous injection every week up to 48 weeks (Treatment Period 2).
干预措施: GP2015 (Drug)
50mg EU-authorized Enbrel
Group 2 will receive treatment with 50mg EU-authorized Enbrel by subcutaneous injection every week up to 24 weeks (Treatment Period 1) after which patients achieving at least a moderate clinical response will be switched to 50 mg GP2015 subcutaneous injection every week up to 48 weeks (Treatment Period 2).
干预措施: GP2015 (Drug)
结局指标
主要结局
Safety: Change in DAS28-CRP Score From Baseline to Week 24 in Patients Treated With GP2015 and Patients Treated With Enbrel
时间窗: treatment period 1: up to 24 weeks
Disease activity score (DAS) 28-CRP is based on 28-joint count (tender and swollen joints), C-reactive protein and patient's assessment of global disease activity, values range from 0.96 to 10.0 while higher values mean a higher disease activity. • A DAS28-CRP value \>5.1 corresponds to a high disease activity • A DAS28-CRP value between 3.2 and 5.1 corresponds to a moderate disease activity • A DAS28-CRP value between 2.6 and 3.2 corresponds to a low disease activity • A DAS28-CRP value \< 2.6 corresponds to remission DAS28-CRP = 0.56 \* sqrt(tender28) + 0.28\* sqrt(swollen28) + 0.36 \* ln(CRP+1) + 0.014 \* GDA + 0.96 where • tender28 and swollen28 are the number of tender and swollen joints as assessed using 28-joint count • CRP is C-reactive protein (mg/l) • GDA is the global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm
次要结局
- Treatment Period 1 - Safety : Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Positive Patients(baseline, week 2, week 4, week 12, week 24)
- Treatment Period 1: Frequency and Severity of Injection Site Reactions in GP2015 and Enbrel(Treatment Period 1, up to 24 weeks)
- Treatment Period 1 - Changes From Baseline in DAS28-CRP and DAS-ESR Scores to Weeks 4, 12 and 24(baseline, Week 4, week 12, week 24)
- Treatment Period 1- Proportion of Patients Achieving EULAR Response(week 4, week 12 and week 24)
- Treatment Period 1- DAS28-CRP and DAS28-erythrocyte Sedimentation Rate (ESR) Scores at Baseline and Weeks 4, 12 and 24;(week 4, 12, 24)
- Treatment Period 1- Proportion of Patients Achieving EULAR/ACR Boolean Remission Criteria(week 4, week 12, week 24)
- Treatment Period 1- Proportion of Patients Achieving ACR20/50/70 Response at Weeks 4, 12 and 24;(Week 4, week 12 and week 24)
- Treatment Period 1 - Proportion of Patients in Each Disease Activity Category as Defined by SDAI(Weeks 4, 12 and 24;)
- Treatment Period 1- Proportion of Patients Achieving DAS28 < 2.6 at Weeks 4, 12 and 24(week 4, week 12 and week 24)
- Treatment Period 1- ACR-N Scores at Weeks 4, 12 and 24;(Weeks 4, 12 and 24;)
- Treatment Period 1 - Health Assessment Questionnaire (HAQ) Index at Baseline, Weeks 4, 12 and 24;(Baseline, Weeks 4, 12 and 24;)
- Treatment Period 1 - Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Relative to Baseline at Weeks 4, 12 and 24;(Baseline, Weeks 4, 12 and 24;)
- Treatment Period 1 - CRP Levels at Baseline and Weeks 4, 12 and 24(Weeks 4, 12 and 24)
- Treatment Period 1 - ESR Levels at Baseline and Weeks 4, 12 and 24(Weeks 4, 12 and 24)
- Treatment Period 2: DAS28-CRP and DAS28-ESR Scores up to Week 48;(Baseline, week 4, week 12, week 24, week 36 and week 48.)
- Treatment Period 2 : Changes From Baseline in DAS28-CRP and DAS28-ESR Scores From Week 4 up to Week 48(week 4, week 12, week 24, week 36, week 48)
- Treatment Period 1 - Proportion of Patients in Each Disease Activity Category as Defined by CDAI(Weeks 4, 12 and 24;)
- Treatment Period 1- Proportion of Patients Achieving HAQ Index in Normal Range (≤ 0.5) at Weeks 4, 12 and 24;(Weeks 4, 12 and 24;)
- Treatment Period 2: Proportion of Patients Achieving EULAR Reponse(week 4, week 12, week 24, week 36 and week 48)
- Treatment Period 2 : Proportion of Patients Achieving DAS28 < 2.6 at Weeks 36 and 48;(week 36 and week 48)
- Treatment Period 2 : Proportion of Patients Achieving EULAR/ACR Boolean Remission Criteria(week 4, week 12, week 24, week 36, week 48)
- Treatment Period 2 : Proportion of Patients Achieving ACR20/50/70 Response at Weeks 36 and 48;(week 36 and week 48)
- Treatment Period 2 : ACR-N Scores at Weeks 36 and 48;(week 36 and week 48)
- Treatment Period 2 : Proportion of Patients in Each Disease Activity Category as Defined by SDAI(baseline, week 4, week 12, week 24, week 36. week 48)
- Treatment Period 2 : Proportion of Patients in Each Disease Activity Category as Defined by CDAI(baseline, week 4, week 12, week 24, week 36 and week 48)
- Treatment Period 2 :Proportion of Patients Achieving HAQ Index in Normal Range (≤ 0.5) at Weeks 36 and 48;(baseline, week 4, week 12, week 24, week 36, week 48)
- Treatment Period 2 :HAQ Index at Weeks 36 and 48;(baseline, week 4, week 12, week 24, week 36, week 48)
- Treatment Period 2 : Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Relative to Baseline at Weeks 36 and 48;(baseline, week 4, week 12, week 24, week 36, week 48)
- Treatment Period 2 : CRP Levels at Week 36 and 48(baseline, week 4, week 12, week 24, week 36, week 48)
- Treatment Period 2 : ESR Levels at Week 36 and 48(baseline, week 4, week 12, week 24, week 36, week 48)
- Safety - Overall Study : Frequency and Severity of Injection Site Reactions in GP2015 and Enbrel(up to 48 weeks)
- Safety : Overall Study: Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Positive Patients(baseline, week 4, week 12, week 24, week 36, week 48)