A Randomized Double-Blind Placebo-controlled Phase Ⅲ Clinical Trial Evaluating the Efficacy and Safety of LNK01001 (Zemprocitinib) in Patient With Moderate-to-Severe Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Biologic Disease-Modifying Antirheumatic Drugs (COURAGE-RA)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 430
- 试验地点
- 1
- 主要终点
- Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 24
研究概览
简要总结
Brief Summary: This is a randomized, double-blind study comparing LNK01001 to placebo in Chinese participants with moderately to severely active rheumatoid arthritis who are on a stable dose of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and have an inadequate response or Intolerance to biologic DMARDs(bDMARDs).
The study objective of Period 1 (Day 1 to Week 24) is to compare the safety and efficacy of LNK01001 12 mg twice daily (BID) versus placebo for the treatment of signs and symptoms of participants with moderately to severely active rheumatoid arthritis (RA) who are on a stable dose of csDMARDs and had an inadequate response to or intolerance to at least 1 bDMARD.
The study objective of Period 2 (Week 24 to Week 76) is to evaluate the long-term safety, tolerability, and efficacy of LNK01001 12 mg BID in participants with RA who completed Period 1.
详细描述
This study includes a 35-day screening period; a 24-week randomized, double-blind, parallel-group, placebo-controlled treatment period (Period 1); a 52-week open label long-term extension period (Period 2); and a 28 to 35-day follow-up period (FU).
Participants who meet eligibility criteria will be randomized in a 1:1 ratio to two treatment groups:
Group 1: LNK01001 12 mg BID (Day 1 to Week 24)， LNK01001 12 mg BID (Week 24 and thereafter)
Group 2: Placebo (Day 1 to Week 24)， LNK01001 12 mg BID (Week 24 and thereafter)
Participants who complete the Week 24 visit (end of Period 1) will enter the extension portion of the study, Period 2, and continue to receive LNK01001 12 mg BID treatment. Starting at Week 12, rescue therapy is allowed if there's less than 20% improvement in both swollen joint count (SJC) and tender joint count (TJC) compared to Baseline. Starting at Week 24, initiation of or change in corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, or adding or increasing doses in up to 2 csDMARDs (concomitant use of up to 2 csDMARDs except the combination of methotrexate and leflunomide) is allowed.
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
- •Participants aged 18 and above.
- •Diagnosis of rheumatoid arthritis (RA) for ≥ 3 months.
- •≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at Screening and baseline visit.
- •Erythrocyte sedimentation rate (ESR) ≥ 28mm/h or high-sensitivity C-Reactive Protein (hsCRP) ≥ ULN at Screening.
- •Participants have been receiving csDMARD therapy ≥ 3 months and on a stable dose for ≥ 4 weeks prior to the first dose of study drug.
- •Have an inadequate response to ≥ 1 bDMARD.
排除标准
- •Subjects who were prior exposure to Janus Kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib) and have evidence showing an inadequate response or intolerance.
- •Subjects who received intra-articular, intramuscular, intravenous, trigger point or tender point, intracapsular, or intra-tendon injections of glucocorticoids within 4 weeks before randomization.
- •Current diagnosis of systemic inflammatory disease other than RA.
- •History of malignancy or current diagnosis of malignancy within 5 years before screening visit.
- •Uncontrolled diabetes, hypertension, kidney disease, liver disease, severe heart disease.
研究组 & 干预措施
LNK01001 12 mg
Period 1: Participants receive LNK01001 12 mg twice daily for 24 weeks. Period 2: Participants will continue on LNK01001 12 mg twice daily from Week 24 to Week 76.
干预措施: LNK01001 (Drug)
Placebo / LNK01001 12 mg
Period 1: Participants receive a placebo twice daily for 24 weeks. Period 2: Participants will switch to receive LNK01001 12 mg twice daily from Week 24 to Week 76.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 24
时间窗: Baseline and Week 24
Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria: 1. 20% improvement in 68-tender joint count; 2. 20% improvement in 66-swollen joint count; and 3. 20% improvement in at least 3 of the 5 following parameters: * Physician global assessment of disease activity * Patient global assessment of disease activity * Patient assessment of pain * Health Assessment Questionnaire - Disability Index (HAQ-DI) * High-sensitivity C-reactive protein (hsCRP).
次要结局
- Change from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at all visits.(Baseline to Week 76.)
- Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at all visits.(Baseline to Week 76.)
- Change from Baseline in Disease Activity Score 28 (DAS28) (CRP) at week 24(Baseline and Week 24)
- Percentage of Participants with an American College of Rheumatology 70% (ACR70) Response at all visits.(Baseline to Week 76.)
- Change from Baseline in the Severity of Morning Stiffness at all visits.(Baseline to Week 76.)
- Percentage of Participants with an American College of Rheumatology 50% (ACR50) Response at week 24(Baseline and Week 24)
- Percentage of Participants with an American College of Rheumatology 20% (ACR20) Response at all visits (except week 24).(Baseline to Week 76 (except week 24).)
- Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at all visits(Baseline to Week 76.)