A Phase IIb Multicenter, Randomized, Double-blind Study of ALX-0061 Administered Subcutaneously as Monotherapy, in Subjects With Moderate to Severe Rheumatoid Arthritis Who Are Intolerant to Methotrexate or for Whom Continued Methotrexate Treatment is Inappropriate
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 251
- 试验地点
- 86
- 主要终点
- Number and Percentage of Subjects With American College of Rheumatology 20 (ACR20) at Week 12
研究概览
简要总结
The primary objective of this study is:
- To assess the efficacy and safety of dose regimens of ALX-0061 monotherapy administered subcutaneously (s.c.) to subjects with active rheumatoid arthritis (RA).
The secondary objectives of this study are:
- To assess the effects of ALX-0061 on quality of life, the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of ALX-0061 and to explore potential dose regimens for ALX-0061 monotherapy, based on safety and efficacy, for further clinical development.
- To obtain parallel descriptive information concerning the efficacy and safety of tocilizumab (TCZ) s.c. in the same clinical trial RA population.
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 (according to the 2010 EULAR/American College of Rheumatology (ACR) classification criteria) for at least 6 months prior to screening, and ACR functional class I-III.
- •Received previous or current treatment with methotrexate (MTX), and is considered intolerant to MTX, or for whom continued treatment with MTX is inappropriate or has contraindications for MTX use.
- •Subjects must not have received MTX for at least 4 weeks before first administration of the study drug.
- •Have active RA with at least 6 swollen and 6 tender joints(66/68 joint count) at the time of screening and baseline
- •Others as defined in the protocol
排除标准
- •Have been treated with DMARDs (Disease Modifying Antirheumatic Drugs)/systemic immunosuppressive drugs during the 4 weeks, or 12 weeks for hydroxychloroquine, chloroquine, or leflunomide (except when an adequate wash-out procedure for leflunomide was completed), prior to first administration of study drug.
- •Have received approved or investigational biological or targeted synthetic DMARD therapies for RA (including tumor necrosis factor alpha-inhibitors, abatacept, rituximab, or Janus kinase [JAK]-inhibitors) 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 (including JAK inhibitors), 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 q2w
ALX-0061 150 mg every 2 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.
干预措施: ALX-0061 (Biological)
TCZ 162 mg q1w or q2w
Open-label TCZ. Injections were to be performed q1w or q2w depending on the approved label per region (last injection was administered at Week 10 or Week 11, depending on the dose regimen).
干预措施: Tocilizumab (Biological)
ALX-0061 225 mg q2w
ALX-0061 225 mg every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.
干预措施: ALX-0061 (Biological)
ALX-0061 150 mg q4w
ALX-0061 150 mg every 4 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.
干预措施: Placebo (Biological)
ALX-0061 150 mg q2w
ALX-0061 150 mg every 2 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.
干预措施: Placebo (Biological)
ALX-0061 150 mg q4w
ALX-0061 150 mg every 4 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit.
干预措施: ALX-0061 (Biological)
结局指标
主要结局
Number and Percentage of Subjects With American College of Rheumatology 20 (ACR20) 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 in Remission Using DAS28 (ESR) at Week 12(Week 12)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Subscale at Week 12(From baseline until Week 12)
- Pharmacodynamics: Concentrations of Soluble Interleukin-6 Receptor (sIL-6R)(From baseline until Week 12)
- Pharmacokinetics: ALX-0061 Concentration in Serum at Week 12(From baseline until Week 12)
- Number and Percentage of Subjects With LDA Using Simplified Disease Activity Index (SDAI) at Week 12(Week 12)
- Number and Percentage of Subjects With LDA Using Clinical Disease Activity Index (CDAI) at Week 12(Week 12)
- Number and Percentage of Subjects With a Treatment-related Treatment-emergent Adverse Event(From baseline until Week 12)
- Number and Percentage of Subjects With LDA Using DAS28 Using Erythrocyte Sedimentation Rate (ESR) at Week 12(Week 12)
- Number and Percentage of Subjects With European League Against Rheumatism (EULAR) (CRP) Good Response at Week 12(Week 12)
- Number and Percentage of Subjects With Low Disease Activity (LDA) Using Disease Activity Score Using 28 Joint Counts (DAS28) Using C-reactive Protein (CRP) at Week 12(Week 12)
- Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12(From baseline until Week 12)
- Change From Baseline in Physical and Mental Component Scores of Short Form Health Survey (SF-36) at Week 12(From baseline until week 12)
- Number and Percentage of Subjects With ACR50 and ACR70 Response at Week 12(Week 12)
- Number and Percentage of Subjects in Remission Using SDAI at Week 12(Week 12)
- Number and Percentage of Subjects in Remission Using CDAI at Week 12(Week 12)
- Number and Percentage of Subjects in Remission Using Boolean Defined Remission Criteria at Week 12(Week 12)
- Number and Percentage of Subjects With Development of a Treatment-emergent Antidrug Antibody Response(From first study drug intake up to and including follow-up (FU), i.e., maximum of 22 weeks (10 weeks of treatment + 12 weeks of FU))
- Number and Percentage of Subjects With Treatment-emergent Adverse Event by Severity(From baseline until Week 12)
- Number of Treatment-emergent Adverse Event by Severity(From baseline until Week 12)
- Number of Treatment-related Treatment-emergent Adverse Event(From baseline until Week 12)