A Phase IIb Multicenter, Randomized, Double-blind, Placebo-Controlled Dose-Range Finding Study of ALX-0061 Administered Subcutaneously in Combination With Methotrexate, in Subjects With Moderate to Severe Rheumatoid Arthritis Despite Methotrexate Therapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 345
- 试验地点
- 7
- 主要终点
- Number and Percentage of Subjects Achieving American College of Rheumatology (ACR) 20 Response at Week 12
研究概览
简要总结
The purpose of this study is to assess the efficacy and safety of dose regimens of ALX-0061 administered subcutaneously (s.c.) in combination with methotrexate (MTX) to subjects with active rheumatoid arthritis (RA) despite MTX therapy, compared with placebo.
To assess the effects of ALX-0061 on quality of life, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of ALX-0061, and to define the optimal dose regimen for ALX-0061, based on safety and efficacy, for further clinical development.
详细描述
Subjects who completed the 24-week assessment period and achieved at least 20% improvement in swollen joint count (SJC) and/or tender joint count (TJC) at Week 24 of study ALX0061-C201 were invited to participate in an open-label extension (OLE) study ALX0061-C203 (NCT02518620), if the study was approved in their country and selection criteria were met.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of RA for at least 6 months prior to screening, and American College of Rheumatology (ACR) functional class I-III
- •Subjects treated with and tolerating MTX
- •Active RA
- •Others as defined in the protocol
排除标准
- •Have been treated with disease-modifying antirheumatic drugs (DMARDs)/systemic immunosuppressives other than MTX.
- •Have received approved or investigational biological or targeted synthetic DMARD therapies for RA less than 6 months prior to screening.
- •Have a history of toxicity, non-tolerance, primary non-response or inadequate response to a biological therapy, or targeted synthetic DMARDs, for RA.
- •Have received prior therapy blocking the interleukin-6 (IL-6) pathway, at any time.
- •Others as defined in the protocol
研究组 & 干预措施
ALX-0061 150 mg q4w + MTX
ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit.
干预措施: ALX-0061 (Biological)
Placebo q2w + MTX
Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit.
干预措施: Placebo (Other)
Placebo q2w + MTX
Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit.
干预措施: Methotrexate (Drug)
ALX-0061 75 mg q4w + MTX
ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit.
干预措施: ALX-0061 (Biological)
ALX-0061 75 mg q4w + MTX
ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit.
干预措施: Placebo (Other)
ALX-0061 75 mg q4w + MTX
ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit.
干预措施: Methotrexate (Drug)
ALX-0061 150 mg q4w + MTX
ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit.
干预措施: Placebo (Other)
ALX-0061 150 mg q4w + MTX
ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit.
干预措施: Methotrexate (Drug)
ALX-0061 150 mg q2w + MTX
ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit.
干预措施: ALX-0061 (Biological)
ALX-0061 150 mg q2w + MTX
ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit.
干预措施: Placebo (Other)
ALX-0061 150 mg q2w + MTX
ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit.
干预措施: Methotrexate (Drug)
ALX-0061 225 mg q2w + MTX
ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24.
The last study drug administration was at the Week 22 visit.
干预措施: ALX-0061 (Biological)
ALX-0061 225 mg q2w + MTX
ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24.
The last study drug administration was at the Week 22 visit.
干预措施: Methotrexate (Drug)
结局指标
主要结局
Number and Percentage of Subjects Achieving American College of Rheumatology (ACR) 20 Response at Week 12
时间窗: Week 12
ACR 20 response is defined as: * 20% improvement in tender joint count (TJC; 68 joints) relative to Week 0 AND * 20% improvement in swollen joint count (SJC; 66 joints) relative to Week 0 AND * 20% improvement in 3 of the following 5 areas relative to Week 0: * Subject's Assessment of Pain (100 mm - visual analogue scale \[VAS\]) * Subject's Global Assessment of Disease Activity (VASPA) * Physician's Global Assessment of Disease Activity (VASPHA) * Subject's assessment of physical function as measured by Health Assessment Questionnaire-Disability Index (HAQ-DI) * C-reactive protein (CRP) level The primary endpoint was analyzed using non-responder imputation (NRI), i.e., subjects with missing ACR20 response at Week 12 were treated as non responders.
次要结局
- Number and Percentage of Subjects With ACR70 Response at Weeks 12 and 24(24 weeks)
- Number and Percentage of Subjects in Remission Using CDAI at Weeks 12 and 24(24 weeks)
- Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Weeks 12 and 24(24 weeks)
- Number of Subjects With Development of a Treatment-emergent Antidrug Antibody Response(from baseline till follow-up (FU) (i.e., 12 weeks after last study drug dosing at Week 22 or after early treatment discontinuation))
- Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Weeks 12 and 24(24 weeks)
- Number and Percentage of Subjects in Remission Using DAS28 (ESR) at Weeks 12 and 24(24 weeks)
- Change From Baseline in Mental Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24(from baseline till Week 24)
- Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R) at Weeks 12 and 24(from baseline till Week 24)
- Number of Treatment-related Treatment-emergent Adverse Events(From first study drug intake until the Week 24 or Early Termination visit. Only safety data through Week 24 is reported as 256 of the 293 subjects who completed the 24-week treatment period rolled-over to the C203 Study and did not perform the FU visit)
- Number and Percentage of Subjects With Low Disease Activity (LDA) Using Disease Activity Score 28 (DAS28) Using C-reactive Protein (CRP) at Weeks 12 and 24(24 weeks)
- Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Weeks 12 and 24(24 weeks)
- Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Weeks 12 and 24(24 weeks)
- Number and Percentage of Subjects With ACR20 Response at Week 24(24 weeks)
- Number and Percentage of Subjects With ACR50 Response at Weeks 12 and 24(24 weeks)
- Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Weeks 12 and 24(24 weeks)
- Number and Percentage of Subjects in Remission Using SDAI at Weeks 12 and 24(24 weeks)
- Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 12 and 24(from baseline till Week 24)
- Change From Baseline in Physical Component Score of Short Form Health Survey (SF-36) at Weeks 12 and 24(from baseline till Week 24)
- Number of Treatment-emergent Adverse Events by Severity(From first study drug intake until the Week 24 or Early Termination visit. Only safety data through Week 24 is reported as 256 of the 293 subjects who completed the 24-week treatment period rolled-over to the C203 Study and did not perform the FU visit)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Weeks 12 and 24(from baseline till Week 24)
- Pharmacokinetics: ALX-0061 Concentration in Serum at Weeks 12 and 24(at Week 12 and Week 24 visits)
- Number and Percentage of Subjects With Treatment-emergent Adverse Events by Severity(From first study drug intake until the Week 24 or Early Termination visit. Only safety data through Week 24 is reported as 256 of the 293 subjects who completed the 24-week treatment period rolled-over to the C203 Study and did not perform the FU visit)
- Number and Percentage of Subjects With Treatment-related Treatment-emergent Adverse Events(From first study drug intake until the Week 24 or Early Termination visit. Only safety data through Week 24 is reported as 256 of the 293 subjects who completed the 24-week treatment period rolled-over to the C203 Study and did not perform the FU visit)