A Phase 2, Randomized, Double-Blind, Placebo-Controlled Multicenter Study of LNK01001 Capsule in Moderately to Severely Active Rheumatoid Arthritis Patients With Inadequate Response or Intolerance to csDMARDs
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 156
- 试验地点
- 1
- 主要终点
- Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at week 12
研究概览
简要总结
This study includes two periods. In Period 1, Participants who meet eligibility criteria will be randomized in a 1:1:1 ratio to receive a twice-daily oral LNK01001 Dose A or LNK01001 Dose B or a matching placebo for 12 weeks. Participants who receive a placebo in Period 1 will be re-randomized at Week 13 in a 1:1 ratio to receive a twice-daily oral LNK01001 Dose A or LNK01001 Dose B for 12 weeks (period 2). Participants who receive LNK01001 ( Dose A and Dose B) in Period 1 will maintain the treatment dose in Period 2.
详细描述
This study includes a 35-day screening period; a 12-week randomized, double-blind, parallel-group, placebo-controlled treatment period (Period 1); a 12-week double-blind period (Period 2); and a 28 to 35-day follow-up period (FU).
Participants who meet eligibility criteria will be randomized in a ratio of 1：1：1 to 3 treatment groups in period 1， the placebo group will be rerandomized in a 1:1 ratio to LNK01001 Dose A or LNK01001 Dose B at week 13.
- Group 1: LNK01001 Dose A BID (Day 1 to Week 12)， LNK01001 Dose A BID (Week 13 and thereafter)
- Group 2：LNK01001 Dose B BID (Day 1 to Week 12)， LNK01001 Dose B BID (Week 13 and thereafter)
- Group 3: Placebo (Day 1 to Week12) ， LNK01001 Dose A BID (Week 13 and thereafter)
- Group 4: Placebo (Day 1 to Week12) ， LNK01001 Dose B BID (Week 13 and thereafter)
Participants who complete the Week 12 visit (end of Period 1) will enter Period 2, and continue to receive LNK01001 Dose A or Dose B treatment. Starting at Week 12, rescue therapy 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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants between ≥ 18 and ≤70 years of age.
- •Diagnosis of RA for ≥ 3 months at screening visit who also fulfill the 2010 American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) classification criteria for RA.
- •≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at Screening and baseline visit.
- •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.
排除标准
- •Subjects who are allergy to any component of the study drug.
- •Subjects who are ACR functional class IV or long-term bedridden/long-term wheelchair.
- •Prior exposure to Janus Kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).
- •Subjects who received intra-articular, intramuscular, intravenous, trigger point or tender point, intracapsular, or intra-tendon injections of glucocorticoids within 8 weeks before randomization.
- •Current use of oral or inhaled glucocorticoids and the daily dose is >10 mg of prednisone (or equivalent dose) or on a not stable dose within 4 weeks before randomization.
- •Current use of Non-steroidal anti-inflammatory drugs and on a not stable dose within 4 weeks before randomization.
- •Subjects who received iguratimod treatment within 4 weeks before randomization.
- •Subjects who received interferon treatment 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.
- •Subject with any major surgery within 4 weeks before randomization or planned major surgery during study; history of chronic pain that may affect study evaluation; previous recipient of an organ transplant.
- •Any clinically significant laboratory or ECG abnormal value, as determined by the Investigator, may interfere with the evaluation of the study results.
研究组 & 干预措施
LNK01001 Dose A
Participants will receive LNK01001 Dose A orally BID for up to 24 weeks.
干预措施: LNK01001 Dose A (Drug)
LNK01001 Dose B
Participants will receive LNK01001 Dose B orally BID for up to 24 weeks.
干预措施: LNK01001 Dose B (Drug)
placebo/LNK01001 Dose A
Participants will receive a placebo orally BID for 12 weeks in Period 1. Participants will be re-randomized at Week 13 in a 1:1 ratio to receive LNK01001 Dose A orally BID for up to 24 weeks.
干预措施: LNK01001 Dose A (Drug)
placebo/LNK01001 Dose A
Participants will receive a placebo orally BID for 12 weeks in Period 1. Participants will be re-randomized at Week 13 in a 1:1 ratio to receive LNK01001 Dose A orally BID for up to 24 weeks.
干预措施: placebo (Drug)
placebo/LNK01001 Dose B
Participants will receive a placebo orally BID for 12 weeks in Period 1. Participants will be re-randomized at Week 13 in a 1:1 ratio to receive LNK01001 Dose B orally BID for up to 24 weeks.
干预措施: LNK01001 Dose B (Drug)
placebo/LNK01001 Dose B
Participants will receive a placebo orally BID for 12 weeks in Period 1. Participants will be re-randomized at Week 13 in a 1:1 ratio to receive LNK01001 Dose B orally BID for up to 24 weeks.
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 12
时间窗: week 12
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 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
- Percentage of Participants With an ACR70(Week1,2,4,8,12)
- Change From Baseline in Disease Activity Score 28 (DAS28)-ESR(Week1,2,4,8,12)
- Percentage of Participants With an ACR50(Week1,2,4,8,12)
- Percentage of Participants With an ACR20(Week1,2,4,8)
- Change From Baseline in Disease Activity Score 28 (DAS28)-CRP(Week1,2,4,8,12)
- Change from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI).(Week1,2,4,8,12)