Chronic Spontaneous Urticaria (CSU)
Conditions
Brief summary
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
Interventions
DRUGTLL-018 tablets
TLL-018 tablets taken orally 10 mg (1 tablet) twice daily
DRUGPlacebo
Placebo taken orally (2 tablets) twice daily for 12 weeks
Sponsors
Hangzhou Highlightll Pharmaceutical Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Aged between 18 and 75. * 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.
Exclusion criteria
* Participants meeting diagnosis criteria of chronic spontaneous urticaria with the following concomitant diseases cannot be enrolled: 1. 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. 2. Clearly defined underlying etiology for chronic urticarias other than CSU. E.g. induced urticaria, including but not limited to artificial urticaria. 3. Any disease, which may have symptoms of urticaria and/or angioedema, including but not limited to urticaria and vasculitis. 4. Suffering from other chronic pruritic diseases that may affect the assessment of efficacy, such as psoriasis, atopic dermatitis, etc. 5. Previous malignancy, herpes zoster, active tuberculosis. * Participants with any of the following prior therapies or medications cannot be enrolled: 1. Have received treatment with JAK inhibitors (e.g., tofacitinib, baricitinib, ruxolitinib, etc.) or BTK inhibitors (e.g., remibrutinib) within 4 weeks prior to randomization; 2. Have received any investigational product within 4 weeks prior to randomization or within 5 elimination half-lives, whichever is longer; 3. Have received omalizumab/omalizumab biosimilar treatment within 4 months prior to randomization; 4. 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; 5. 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-018. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in weekly Itch Severity Score at Week 12 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in weekly Hive Severity Score | 12 weeks | Change from baseline in weekly hive severity score (HSS7) at week 1, 2, 4, 8, and 12. The weekly hive severity score (HSS7) ranges from 0 to 21 (higher = worse). |
| Proportion of Participants With weekly Urticaria Activity Score ≤ 6 | 12 weeks | Proportion of participants achieve disease activity control (weekly Urticaria Activity Score≤6) at Week 1, 2, 4, 8, and 12. The weekly Urticaria Activity Score 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. |
| Proportion of Participants With weekly Urticaria Activity Score = 0 | 12 weeks | Proportion of participants achieve achieve complete absence of hives and itch (weekly Urticaria Activity Score=0) at Week 1, 2, 4, 8, and 12. The weekly Urticaria Activity Score 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. |
| Change from baseline in Dermatology Life Quality Index score | 12 weeks | Change from baseline in Dermatology Life Quality Index score at week 4, 8,and 12. The Dermatology Life Quality Index (DLQI) is a widely used patient-reported outcome (PRO) instrument with a range of 0-30, higher scores indicate greater impairment of quality of life. |
| Proportion of Participants With Dermatology Life Quality Index score=0/1 | 12 weeks | Proportion of Participants With Dermatology Life Quality Index score=0/1 at week 4, 8, and 12. The Dermatology Life Quality Index (DLQI) is a widely used patient-reported outcome (PRO) instrument with a range of 0-30, higher scores indicate greater impairment of quality of life. |
Outcome results
None listed