A Randomized, Double-blind, Phase II Study of Efficacy and Safety of TLL-018 in Moderate-to-Severe CSU Participants With Inadequate Response to Second-Generation H1 Antihistamines
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 140
- 主要终点
- Change from baseline in weekly Itch Severity Score at Week 12
研究概览
简要总结
The goal of this clinical trial is to learn if different doses of TLL-018 works to treat in moderate-to-severe chronic spontaneous urticaria (CSU) participants . It will also learn about the safety of TLL-018. The main questions it aims to answer are:
Which is the best regimen of TLL-018 administration in reducing or eliminating symptoms (hives, itch, and/or angioedema) ? What medical problems do participants have when taking TLL-018? Researchers will compare different doses of TLL-018, and placebo (a look-alike substance that contains no drug).
Participants will:
Take TLL-018 or a placebo every day for 12 weeks Visit the clinic once every 4 weeks for checkups and tests Keep a diary of their symptoms
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged between 18 and
- •Diagnosis of CSU refractory to second-generation H1-AH.
- •CSU diagnosis for ≥ 6 months.
- •The presence of itch and hives despite current use of an approved dose of H1-AH prior to randomization.
- •UAS7 score (range 0-42) ≥ 16 and ISS7 (range 0-21) ≥ 8 during 7 days prior to randomization.
- •Participants were required to take a stable standard dose of a second generation H1-AH concomitantly according to local guidelines.
- •Willing and able to complete UPDD during the study; participants must not have more than one missing UPDD symptom score (either morning or evening) within the 7-day period prior to randomization.
- •Evidence of urticaria confirmed by the investigator prior to randomization.
- •Women of Child Bearing Potential (WOCBP) should not be pregnant or breastfeeding and the pregnancy test should be negative before randomization.
- •Participants and their partners must agree to have adequate barrier contraception during the whole treatment period and at least 90 days after treatment; subjects should avoid the sperm or ovum donation for at least six months after treatment.
- •The trial participant understands the informed consent form and voluntarily agrees to participate in the study.
排除标准
- •Participants meeting diagnosis criteria of chronic spontaneous urticaria with the following concomitant diseases cannot be enrolled:
- •Progressive or uncontrolled signs or symptoms of renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiovascular, neurologic, psychiatric, or cerebral disease, as judged by the investigator to place the subject at unacceptable risk by study participation.
- •Clearly defined underlying etiology for chronic urticarias other than CSU. E.g. induced urticaria, including but not limited to artificial urticaria.
- •Any disease, which may have symptoms of urticaria and/or angioedema, including but not limited to urticaria and vasculitis.
- •Suffering from other chronic pruritic diseases that may affect the assessment of efficacy, such as psoriasis, atopic dermatitis, etc.
- •Previous malignancy, herpes zoster, active tuberculosis.
- •Participants with any of the following prior therapies or medications cannot be enrolled:
- •Have received treatment with JAK inhibitors (e.g., tofacitinib, baricitinib, ruxolitinib, etc.) or BTK inhibitors (e.g., remibrutinib) within 4 weeks prior to randomization;
- •Have received any investigational product within 4 weeks prior to randomization or within 5 elimination half-lives, whichever is longer;
- •Have received omalizumab/omalizumab biosimilar treatment within 4 months prior to randomization;
- •Have received biologics with potential therapeutic effects for chronic spontaneous urticaria (e.g., dupilumab, etc.) within 3 months prior to randomization or within 5 elimination half-lives, whichever is longer;
- •Have received immunosuppressive or immunomodulatory drug therapy within 4 weeks prior to randomization, e.g., systemic corticosteroids, etc.
- •Known allergy to any active ingredients or excipients of H1-AH or TLL-
- •Abnormal laboratory test results that may interfere with the conduct of the study by the assessment from the investigator.
- •Any other situation or condition that, in the investigator's judgment, would render the participant unsuitable for study participation.
研究组 & 干预措施
Arm A
TLL-018 tablets taken orally 10 mg (1 tablet) twice daily for 12 weeks
干预措施: TLL-018 tablets (Drug)
Arm B
TLL-018 tablets taken orally 20 mg (2 tablets) twice daily for 4 weeks, followed by TLL-018 tablets taken orally 10 mg (1 tablet) twice daily for 8 weeks
干预措施: TLL-018 tablets (Drug)
Arm C
TLL-018 tablets taken orally 20 mg (2 tablets) twice daily for 12 weeks
干预措施: TLL-018 tablets (Drug)
Arm D
Placebo taken orally (2 tablets) twice daily for 12 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Change from baseline in weekly Itch Severity Score at Week 12
时间窗: 12 weeks
The weekly Itch Severity Score (ISS7) is the itch severity score for 7 days, and it ranges from 0 to 21 (higher = worse itch).
Change from baseline in weekly Urticaria Activity Score at Week 12
时间窗: 12 weeks
The weekly Urticaria Activity Score (UAS7) is a scoring system to evaluate urticaria signs and symptoms. It is based on scoring wheals (hive severity score) and itch (itch severity score) separately on a scale of 0 (no signs/symptoms) to 3 (intense signs/symptoms) over 7 days. The final score is calculated by adding together the daily scores, which can range from 0 to 6, for 7 days. This results in a maximum total score of 42, and a minimum possible score of 0.
次要结局
- Change from baseline in weekly Hive Severity Score(12 weeks)
- Proportion of Participants With weekly Urticaria Activity Score ≤ 6(12 weeks)
- Proportion of Participants With weekly Urticaria Activity Score = 0(12 weeks)
- Change from baseline in Dermatology Life Quality Index score(12 weeks)
- Proportion of Participants With Dermatology Life Quality Index score=0/1(12 weeks)