A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase 2 Proof-of-Concept Study to Evaluate Safety, Tolerability, and Efficacy of GS-5718 on Background Therapy With Conventional Synthetic Disease-modifying Antirheumatic Drug(s) (csDMARDs) in Participants With Active Rheumatoid Arthritis Who Have an Inadequate Response to Biologic DMARD(s) Treatment
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Change From Baseline in Disease Activity Score (DAS) Based on 28 Joints Using C-reactive Protein (CRP) DAS28 (CRP) at Week 12
研究概览
简要总结
The primary objective of the study is to evaluate the effect of GS-5718 versus placebo for the treatment of rheumatoid arthritis (RA) as measured by change from baseline in Disease Activity Score (DAS) based on 28 joints using C-reactive protein (CRP) (DAS28[CRP]) at Week 12.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of rheumatoid arthritis (RA) ≥ 3 months prior to screening fulfilling the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA
- •Rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPA) positivity
- •Individual fulfills all of the following minimum disease activity criteria:
- •≥ 6 swollen joints (from a swollen joint count based on 66 joints [SJC66]) provided this would also fulfill ≥ 4 swollen joints (from a swollen joint count based on 28 joints [SJC28]) at screening and Day 1, and
- •≥ 6 tender joints (from a tender joint count based on 68 joints [TJC68]), provided this would also fulfill ≥ 4 tender joints (from a tender joint count based on 28 joints [TJC28]) at screening and Day 1, and
- •hsCRP > upper limit of normal at screening
- •Received at least one bDMARD for the treatment of RA to which there is a lack of efficacy and/or intolerance.
排除标准
- •Individuals who do not qualify per the tofacitinib label and/or local guidelines should not be enrolled.
- •Prior exposure to any Janus kinase inhibitor
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
GS-5718 Dose A
Participants will receive GS-5718 Dose A once daily + placebo to match (PTM) GS-5718 Dose B once daily + PTM tofacitinib twice daily for up to 12 weeks.
干预措施: GS-5718 (Drug)
GS-5718 Dose A
Participants will receive GS-5718 Dose A once daily + placebo to match (PTM) GS-5718 Dose B once daily + PTM tofacitinib twice daily for up to 12 weeks.
干预措施: Placebo to match GS-5718 (Drug)
GS-5718 Dose A
Participants will receive GS-5718 Dose A once daily + placebo to match (PTM) GS-5718 Dose B once daily + PTM tofacitinib twice daily for up to 12 weeks.
干预措施: Placebo to match Tofacitinib (Drug)
GS-5718 Dose B
Participants will receive GS-5718 Dose B once daily + PTM GS-5718 Dose A once daily + PTM tofacitinib twice daily for up to 12 weeks.
干预措施: GS-5718 (Drug)
GS-5718 Dose B
Participants will receive GS-5718 Dose B once daily + PTM GS-5718 Dose A once daily + PTM tofacitinib twice daily for up to 12 weeks.
干预措施: Placebo to match GS-5718 (Drug)
GS-5718 Dose B
Participants will receive GS-5718 Dose B once daily + PTM GS-5718 Dose A once daily + PTM tofacitinib twice daily for up to 12 weeks.
干预措施: Placebo to match Tofacitinib (Drug)
Tofacitinib
Participants will receive tofacitinib 5 mg twice daily + PTM GS-5718 (Dose A + Dose B) once daily for up to 12 weeks.
干预措施: Placebo to match GS-5718 (Drug)
Tofacitinib
Participants will receive tofacitinib 5 mg twice daily + PTM GS-5718 (Dose A + Dose B) once daily for up to 12 weeks.
干预措施: Tofacitinib 5 mg (Drug)
Placebo
Participants will receive PTM GS-5718 (Dose A + Dose B) once daily + PTM tofacitinib twice daily for up to 12 weeks.
干预措施: Placebo to match GS-5718 (Drug)
Placebo
Participants will receive PTM GS-5718 (Dose A + Dose B) once daily + PTM tofacitinib twice daily for up to 12 weeks.
干预措施: Placebo to match Tofacitinib (Drug)
结局指标
主要结局
Change From Baseline in Disease Activity Score (DAS) Based on 28 Joints Using C-reactive Protein (CRP) DAS28 (CRP) at Week 12
时间窗: Baseline, Week 12
The DAS28(CRP) is a measure of the participant's disease activity calculated using the tender joint counts (28 joints), swollen joint counts (28 joints), subject's global assessment (SGA) of disease activity assessed using visual analog scale (VAS) on a scale of 0-100 (0 indicating no arthritis and 100 indicating extremely active arthritis), and high-sensitivity C-reactive protein (hsCRP) measurement for a total possible score of 1 to 9.4. Higher values indicate higher disease activity. A negative change from baseline indicates improvement.
次要结局
- Percentage of Participants Who Achieve American College of Rheumatology 20% Improvement (ACR20) Response at Week 12(Week 12)
- Percentage of Participants Who Achieve SDAI ≤ 3.3 at Week 12(Week 12)
- Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 12(Baseline, Week 12)
- Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 12(Baseline, Week 12)
- Percentage of Participants Who Achieve DAS28(CRP) ≤ 3.2 at Week 12(Week 12)
- Pharmacokinetic (PK) Parameter: AUCtau of GS-5718(Up to Week 12)
- PK Parameter: AUCtau of Methotrexate (MTX)(Up to Week 8)
- PK Parameter: Cmax of GS-5718(Up to Week 12)
- PK Parameter: Cmax of MTX(Up to Week 8)
- Percentage of Participants Who Achieve ACR 50% Improvement (ACR50) Response at Week 12(Week 12)
- Percentage of Participants Who Achieve ACR 70% Improvement (ACR70) Response at Week 12(Week 12)
- Percentage of Participants Who Achieve SDAI ≤ 11 at Week 12(Week 12)
- Percentage of Participants Who Achieve CDAI ≤ 2.8 at Week 12(Week 12)
- Percentage of Participants Who Achieve CDAI ≤ 10 at Week 12(Week 12)
- Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 12(Baseline, Week 12)
- Percentage of Participants Who Achieve DAS28(CRP) < 2.6 at Week 12(Week 12)