Rheumatoid Arthritis: A Phase 2 Study to Investigate the Safety and Efficacy of ABBV-105 Given Alone or in Combination With Upadacitinib (ABBV-599 Combination) With a Background of Conventional Synthetic DMARDs in Subjects With Active Rheumatoid Arthritis With Inadequate Response or Intolerance to Biologic DMARDs
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 242
- 试验地点
- 115
- 主要终点
- Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12
研究概览
简要总结
This was a phase 2 study to evaluate the safety and efficacy of elsubrutinib (ELS) and ABBV-599 (ELS plus upadacitinib [UPA]) vs placebo on a background of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) for the treatment of signs and symptoms of rheumatoid arthritis (RA) at 12 weeks in biological disease-modifying anti-rheumatic drugs (bDMARD)-inadequate response (bDMARD-IR) or bDMARD-intolerant participants with moderately to severely active RA and to define optimal dose for further development.
详细描述
This was a 12-week, randomized, double-blind, parallel-group, Phase 2, dose exploratory, multicenter study. Participants who met eligibility criteria were randomized in a 3:2:2:2:2:1 ratio to 1 of 6 treatment groups: ABBV-599 [UPA 15 mg/ELS 60 mg]); ELS 60 mg/UPA placebo; ELS 20 mg/UPA placebo; ELS 5 mg/UPA placebo; UPA 15 mg/ELS placebo; and ELS placebo/UPA placebo. The study included a 35-day maximum screening period and a 12-week treatment period with 30-day follow-up.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of rheumatoid arthritis (RA) for ≥ 3 months based on the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA
- •Participant meets the following minimum disease activity criteria:
- •≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits
- •High-sensitivity C-reactive protein (hsCRP) ≥ 3 mg/L (central lab) at Screening Visit
- •Participants must have been treated for ≥ 3 months with ≥ 1 biologic disease-modifying anti-rheumatic drug (bDMARD) therapy but continue to exhibit active RA or had to discontinue due to intolerability or toxicity, irrespective of treatment duration
- •Participants must have been receiving conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) therapy ≥ 3 months and on a stable dose for ≥ 4 weeks prior to the first dose of study drug
- •Participants must have discontinued all bDMARDs prior to the first dose of study drug
排除标准
- •Participant has prior exposure to any Janus Kinase (JAK) inhibitor for greater than 2 weeks (including but not limited to upadacitinib, tofacitinib, baricitinib, and filgotinib). A washout period of ≥ 30 days is required for any JAK inhibitor prior to the first dose of study drug.
研究组 & 干预措施
ELS placebo/UPA placebo
Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
干预措施: Placebo for elsubrutinib (Drug)
ELS placebo/UPA placebo
Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
干预措施: Placebo for upadacitinib (Drug)
UPA 15 mg/ELS 60 mg
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks
干预措施: Elsubrutinib (Drug)
UPA 15 mg/ELS 60 mg
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks
干预措施: Upadacitinib (Drug)
ELS 60 mg/UPA placebo
60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
干预措施: Elsubrutinib (Drug)
ELS 60 mg/UPA placebo
60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
干预措施: Placebo for upadacitinib (Drug)
ELS 20 mg/UPA placebo
20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
干预措施: Elsubrutinib (Drug)
ELS 20 mg/UPA placebo
20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
干预措施: Placebo for upadacitinib (Drug)
ELS 5 mg/UPA placebo
5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
干预措施: Elsubrutinib (Drug)
ELS 5 mg/UPA placebo
5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
干预措施: Placebo for upadacitinib (Drug)
UPA 15 mg/ELS placebo
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks
干预措施: Upadacitinib (Drug)
UPA 15 mg/ELS placebo
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks
干预措施: Placebo for elsubrutinib (Drug)
结局指标
主要结局
Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12
时间窗: Baseline, Week 12
The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from baseline indicates improvement in disease activity.
次要结局
- Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12(At Week 12)
- Change From Baseline in Morning Stiffness Severity(Baseline, Week 2, Week 4, Week 8, and Week 12)
- Change From Baseline in Simplified Disease Activity Index (SDAI)(Baseline, Week 2, Week 4, Week 8, and Week 12)
- Change From Baseline in Clinical Disease Activity Index (CDAI)(Baseline, Week 2, Week 4, Week 8, and Week 12)
- Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria(Week 2, Week 4, Week 8, and Week 12)
- Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12(At Week 12)
- Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria(Week 2, Week 4, Week 8, and Week 12)
- Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response(Baseline, Week 2, Week 4, Week 8, and Week 12)
- Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response(Baseline, Week 2, Week 4, Week 8, and Week 12)
- Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response(Baseline, Week 2, Week 4, Week 8, and Week 12)
- Change From Baseline in Tender Joint Count 68 (TJC68)(Baseline, Week 2, Week 4, Week 8, and Week 12)
- Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS])(Baseline, Week 2, Week 4, Week 8, and Week 12)
- Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA)(Baseline, Week 2, Week 4, Week 8, and Week 12)
- Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP)(Baseline, Week 2, Week 4, Week 8, and Week 12)
- Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP])(Baseline, Week 2, Week 4, Week 8, and Week 12)
- Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR)(Baseline, Week 2, Week 4, Week 8, and Week 12)
- Change From Baseline in Swollen Joint Count 66 (SJC66)(Baseline, Week 2, Week 4, Week 8, and Week 12)
- Change From Baseline in Patient's Global Assessment of Disease Activity (PGA)(Baseline, Week 2, Week 4, Week 8, and Week 12)
- Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI)(Baseline, Week 2, Week 4, Week 8, and Week 12)
- Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI)(Baseline, Week 2, Week 4, Week 8, and Week 12)
- Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission(Baseline, Week 2, Week 4, Week 8, and Week 12)