NCT05133297已完成2 期
A Phase 2A, Randomized, Double-blind, Double-dummy, Tofacitinib-parallel-group Study to Evaluate the Safety and Efficacy of TLL-018 in Active Rheumatoid Arthritis Who Had an Inadequate Response or Intolerance to Methotrexate.
Hangzhou Highlightll Pharmaceutical Co., Ltd1 个研究点 分布在 1 个国家目标入组 101 人开始时间: 2022年2月16日最近更新:
适应症
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 101
- 试验地点
- 1
- 主要终点
- Number of Participants American College of Rheumatology 50% (ACR50) Response at Week 12
研究概览
简要总结
This is a randomized, double-blind, double-dummy, tofacitinib-parallel-group, phase 2A study to assess the safety and efficacy of TLL-018 in active rheumatoid arthritis subject who had an inadequate response or intolerance to methotrexate.
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
- Triple (Participant, Care Provider, 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
- •Diagnosed with RA based on either the 1987-revised American College of Rheumatology (ACR) classification criteria or the 2010 ACR/European League against Rheumatism (EULAR) criteria and have an inadequate response or intolerance to methotrexate.
- •Subjects must have been receiving oral or parenteral methotrexate therapy ≥ 3 months and on a stable prescription of 7.5 to 25 mg/week for at least 4 weeks prior to Baseline Visit.
- •Have active RA as defined by the following minimum disease activity criteria:
- •≥ 6 swollen joints (based on 66 joint counts) at Screening and Baseline Visits;
- •≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits;
- •high-sensitivity C-reactive protein (hsCRP) > upper limit of normal (ULN) OR positive for both rheumatoid factor and anti-cyclic citrullinated peptide (CCP) at Screening.
- •For subjects with inadequate response to methotrexate, subjects must have discontinued all oral disease-modifying anti-rheumatic drugs (DMARDs) prior to Baseline Visit as specified below or for at least five times the mean terminal elimination half-life of a drug, whichever is longer:
- •≥4 weeks prior to Baseline Visit for minocycline, penicillamine, sulfasalazine, hydroxychloroquine, chloroquine, azathioprine, gold formulations, cyclophosphamide;
- •≥12 weeks prior to Baseline Visit for leflunomide if no elimination procedure was followed, or adhere to a washout procedure (i.e., 11 days washout with colestyramine, or 30 days washout with activated charcoal).
- •The organ function level must meet the following requirements:
- •Bone marrow: Blood routine results showed hemoglobin ≥90g/L, platelet ≥100×109/L, neutrophil absolute count ≥1.5×109/L; Liver: serum bilirubin ≤1.5 times the upper limit of normal value, aspartate aminotransferase (AST) ≤1.5 times the upper limit of normal value, alanine aminotransferase (ALT) ≤1.5 times the upper limit of normal value; Serum creatinine <1.5 times the upper limit of normal value; Urine protein ≤1+, if urine protein >1+, urine protein should be collected for 24 hours, the total amount should be ≤1 g. Female subjects of childbearing potential must test negative for pregnancy.
排除标准
- •History of Felty syndrome (Rheumatoid arthritis - Splenomegaly syndrome).
- •A history of herpes zoster or disseminated herpes simplex.
- •Treatment with any JAK inhibitor (tofacitinib, baricitinib, ruxolitinib) within 2 weeks prior to study start.
- •Subjects have severe, progressive or uncontrollable symptoms of kidney, liver, blood, gastrointestinal, lung, cardiovascular, neurological or brain disease.
- •Current treatment or treatment within 4 weeks or 5 half-lives (whichever is longer) prior to the first dose of study medication with another investigational medication or current enrollment in another investigational drug protocol.
- •If the laboratory T-Spot test (or other TB diagnostic test) is positive, the investigator will determine the activity based on the history and clinical manifestations, and the patients diagnosed as active TB should be excluded.
- •Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibody.
- •Pregnant or breastfeeding female.
研究组 & 干预措施
Sequence 1
Experimental
TLL018 tablets, 1piece,BID
干预措施: TLL-018 (Drug)
Sequence 2
Experimental
TLL018 tablets, 2pieces, BID
干预措施: TLL-018 (Drug)
Sequence 3
Experimental
TLL018 tablets, 3pieces, BID
干预措施: TLL-018 (Drug)
Sequence 4
Active Comparator
TOFA tablets, 1pieces, BID
干预措施: Tofacitinib (Drug)
结局指标
主要结局
Number of Participants American College of Rheumatology 50% (ACR50) Response at Week 12
时间窗: Week 12
A participant was a responder if the following 3 criteria for improvement from baseline were met: * ≥50% improvement in 68-tender joint count; * ≥50% improvement in 66-swollen joint count; and * ≥50% improvement in at least 3 of the 5 following parameters:
次要结局
- Number of Participants American College of Rheumatology 20% (ACR20) Response(Week 4, 8, 12, 16, 20 and 24)
- Number of Participants Achieving American College of Rheumatology 70% (ACR70) Response(Weeks 4, 8, 12, 16, 20 and 24)
- Number of Participants Achieving American College of Rheumatology 50% (ACR50) Response(Weeks 4, 8, 12, 16, 20 and 24)
- Change From Baseline in Clinical Disease Activity Index (CDAI)(Weeks 4, 8, 12, 16, 20 and 24)
- Change From Baseline in Disease Activity Score Based on 28-Joints Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP)(Weeks 4, 8, 12, 16, 20 and 24)
- Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score(Weeks 4, 8, 12, 16, 20 and 24)
- Percent Change From Baseline in Participant's Assessment of Pain Based on Visual Analog Scale (VAS) Score(Weeks 4, 8, 12, 16, 20 and 24)
- Change From Baseline in Patient's Global Assessment of Arthritis(Weeks 4, 8, 12, 16, 20 and 24)
- Change From Baseline in Physician's Global Assessment of Arthritis(Weeks 4, 8, 12, 16, 20 and 24)
研究者
研究点 (1)
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