An Open-label, Long-term Extension Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of TLL-018 in Patients With Rheumatoid Arthritis
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 350
- 试验地点
- 1
- 主要终点
- Number of occurrences and Percentage of Participants with AEs and SAEs
研究概览
简要总结
The primary objective of the study is to evaluate the long-term safety, tolerability, and efficacy of TLL-018 in patients with rheumatoid arthritis (RA) who have completed a preceding randomized controlled trial with TLL-018.
详细描述
This is an open-label extension study to assess the long-term safety, tolerability, and efficacy of TLL-018 in adults with RA who have completed Study TLL-018-301(NCT06020144), a phase 3 randomized controlled trial with TLL-018.
The study includes three parts: screening period, treatment period and follow-up period. All participants will be treated with TLL-018 20 mg twice daily (BID) for 78 weeks.
Safety assessment will be conducted at 6, 12, 24, 36, 48, 60, 72, 78 weeks, including physical examination, collection of vital signs, laboratory tests, AEs, SAEs, etc.
Efficacy evaluation will be performed at weeks 12, 24, 36, 48, 60, 72, and 78, including joint assessment, PGA, PtGA, VAS, HAQ-DI questionnaires, SF-36 scale, morning stiffness assessment, DAS28-hsCRP, CDAI, SDAI, ACR20/50/70 response assessment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Subjects have completed TLL-018-301 study within 3 months;
- •Age (at the time of consent):>＝18 years of age, <＝75 years of age;
- •Female subjects of childbearing potential (WOCBP), who should not be pregnant or breastfeeding, should not enter the study until after pregnancy testing (e.g., HCG beta subunit-based monitoring);
- •All subjects and their partners voluntarily use contraception as deemed effective by the investigator for at least 90 days from the first dose of the investigational drug to the last dose of the investigational drug (Appendix I); no sperm or egg donation is planned by the subject for at least 6 months from the screening period to the last dose of the investigational drug.
- •Subjects can understand the informed consent form, volunteer to participate in the study and sign the informed consent form.
排除标准
- •Subjects have had severe allergic reaction related to the investigational drug during the TLL-018-301 study;
- •Subjects have had herpes zoster, a major cardiovascular event (MACE), thromboembolism, or lymphoproliferative disorders from the time of TLL-018-301 study to the screening of OLE study;
- •Subjects have a clinically significant cardiovascular, respiratory, or any other serious and/or non-stable disease, and there is security risk for subjects to participate in this study judged by the investigator;
- •Subjects have abnormal and clinically significant laboratory test values at screening;
- •Subjects who have taken traditional Chinese medicines, csDMARDs, immunosuppressive drugs, potent opioids, and other JAK inhibitors (except the investigational drugs in TLL-018-301 study) within 1 week before taking the first dose of the investigational drug in OLE study;
- •Subjects have treated with flunomide, any bDMARDs, interferon, and other injected immunosuppressive drugs from TLL-018-301 study to the screening of OLE study;
- •Subjects who have received any live vaccine within 2 months prior to taking the first dose of the investigational drug or who plan to receive a live vaccine during the study;
- •Subjects have had active tuberculosis infection without evidence of clinical cure; have suspected tuberculosis symptoms judged by the investigator; have latent tuberculosis infection (LTBI) but not received preventive treatment regimens within 3 years prior to screening or not completed a course of therapy.
研究组 & 干预措施
TLL-018
Participants received a two-stage treatment period in Study TLL-018-301, with treatment of 24 weeks of TLL-018 20 mg BID or tofacitinib 5 mg BID in Stage 1. In Stage 2, the participants with tofacitinib who didn't achieve ACR50 were transferred to TLL-018, and other participants maintained the original treatment. Upon completion of Study TLL-018-301, qualified participants can enter the OLE study, and all participants will receive TLL-018 20 mg BID, i.e., 2 tablets of TLL-018 10 mg orally twice daily, for 78 weeks.
干预措施: TLL-018 (Drug)
结局指标
主要结局
Number of occurrences and Percentage of Participants with AEs and SAEs
时间窗: At Weeks 6, 12, 24, 36, 48, 60, 72, 78
Evaluation includes vital signs, physical examination, ECG examination, laboratory tests, AE, SAE, etc.
次要结局
- Change From Baseline in Patient's Global Assessment of Disease Activity (PtGA) Over Time(Baseline (of the preceding TLL-018-301 study）and Weeks 12, 24, 36, 48, 60, 72, 78)
- Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response Over Time(At Weeks 12, 24, 36, 48, 60, 72, 78)
- Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response Over Time(At Weeks 12, 24, 36, 48, 60, 72, 78)
- Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response Over Time(At Weeks 12, 24, 36, 48, 60, 72, 78)
- Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score-28 (DAS28[CRP]) Over Time(At Weeks 12, 24, 36, 48, 60, 72, 78)
- Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score-28 (DAS28[CRP]) Over Time(At Weeks 12, 24, 36, 48, 60, 72, 78)
- Change From Baseline in Disease Activity Score Based on CRP (DAS28 [CRP]) Over Time(Baseline (of the preceding TLL-018-301 study）and Weeks 12, 24, 36, 48, 60, 72, 78)
- Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Over Time(Baseline (of the preceding TLL-018-301 study）and Weeks 12, 24, 36, 48, 60, 72, 78)
- Change From Baseline in Clinical Disease Activity Index (CDAI) Over Time(Baseline (of the preceding TLL-018-301 study）and Weeks 12, 24, 36, 48, 60, 72, 78)
- Change From Baseline in Simplified Disease Activity Index (SDAI) Over Time(Baseline (of the preceding TLL-018-301 study）and Weeks 12, 24, 36, 48, 60, 72, 78)
- Change From Baseline in Patient's Assessment of Pain Over Time(Baseline (of the preceding 301 study）and Weeks 12, 24, 36, 48, 60, 72, 78)
- Change From Baseline in Physician's Global Assessment of Disease Activity (PGA) Changes From Baseline in SF-36 Score(Baseline (of the preceding TLL-018-301 study）and Weeks 12, 24, 36, 48, 60, 72, 78)
- Changes From Baseline in SF-36 Score Over Time(Baseline (of the preceding TLL-018-301 study）and Weeks 24, 48, 78)
- Changes From Baseline in Morning Stiffness Over Time(Baseline (of the preceding TLL-018-301 study）and Weeks 24, 48, 78)