A Phase Ib/IIa Study Assessing the Rapid Onset Characteristics of TLL-018 for Moderate-to-Severe CSU With Inadequate Response to Second-Generation H1 Antihistamines

NCT07665996 | Not Yet Recruiting Phase 1

• 1 other identifier: TLL-018-206
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate the rapid onset characteristics of TLL-018 in moderate-to-severe CSU with inadequate response to second-generation H1 antihistamines. The main objectives are: To evaluate the rapid onset characteristics of TLL-018 in participants with moderate-to-severe chronic spontaneous urticaria. To evaluate the safety profile of TLL-018 in participants with moderate-to-severe chronic spontaneous urticaria. To evaluate the pharmacokinetic (PK) profile of TLL-018 in participants with moderate-to-severe chronic spontaneous urticaria. Participants will be randomly allocated at a 1:1:1 ratio to receive TLL-018 10 mg, TLL-018 20 mg, or placebo orally after meals.

Conditions

Chronic Spontaneous Urticaria (CSU)

Outcome Measures

Primary Outcomes (19)

• Time to first achievement of ≥1-point reduction from baseline in in-clinic Itch Severity Scale after first dose

  Time from first dose until the first clinic assessment where a ≥1-point reduction from baseline in Itch Severity Scale (ISS, range 0-4; higher = worse itch) at in-clinic evaluation.

  First dose up to day 2

• Time to first ≥1-point reduction from baseline in in-clinic Hive Severity Scale after first dose

  Time from first dose to the first in-clinic assessment with ≥1-point reduction from baseline on Hive Severity Scale (HSS, 0-4).

  First dose up to day 2

• Change from baseline in in-clinic Itch Severity Scale post first dose

  Mean change from baseline of in-clinic ISS (0-4) at scheduled timepoints after first dose.

  First dose up to 8 hours post first dose

• Change from baseline in in-clinic Hive Severity Scale post first dose

  Mean change from baseline of in-clinic Hive Severity Scale (0-4) at scheduled timepoints after first dosing.

  First dose up to 8 hours post first dose

• Change from baseline in in-clinic Numeric Rating Scale post first dose

  Mean change from baseline of in-clinic Numeric Rating Scale (clinic NRS, 0-10) at scheduled timepoints after first dosing.

  First dose up to 8 hours post first dose

• Proportion of participants with ≥1-point reduction from baseline in in-clinic Itch Severity Scale post first dose

  Percentage of participants achieving ≥1-point reduction from baseline on in-clinic Itch Severity Scale (0-4) at each in-clinic timepoint post first dose.

  First dose up to 8 hours post first dose

• Proportion of participants with ≥1-point reduction from baseline in in-clinic Hive Severity Scale post first dose

  Hive Severity Scale (HSS, range 0-4; higher = worse hive)

  First dose up to 8 hours post first dose

• Proportion of participants with ≥3-point reduction from baseline in in-clinic Numeric Rating Scale post first dose (baseline clinic Numeric Rating Scale ≥3)

  Percentage of participants with baseline NRS score ≥3 who attain ≥3-point reduction from baseline on NRS (0-10) at each in-clinic assessment after first dose.

  First dose up to 8 hours post first dose

• Proportion of participants with ≥4-point reduction from baseline in in-clinic Numeric Rating Scale post first dose (baseline clinic Numeric Rating Scale ≥4)

  Percentage of participants with baseline Numeric Rating Scale score ≥4 who attain ≥4-point reduction from baseline on NRS (0-10) at each in-clinic assessment after first dose.

  First dose up to 8 hours post first dose

• Change from baseline in Itch Severity Scale at Day 0.5, Day 1, Day 1.5 post first dose

  Itch Severity Scale (ISS, range 0-4; higher = worse itch)

  First dose up to 1.5 days post first dose

• Change from baseline in Hive Severity Scale at Day 0.5, Day 1, Day 1.5 post first dose

  Hive Severity Scale (HSS, range 0-4; higher = worse hive)

  First dose up to 1.5 days post first dose

• Change from baseline in Worst Itch Numeric Rating Scale at Day 0.5, Day 1, Day 1.5 post first dose

  Itch Numeric Rating Scale (NRS): from 0 (no itch) to 10 (worst imaginable itch)

  First dose up to 1.5 days post first dose

• Change from baseline in in-clinic Itch Severity Scale at 2 hours post second dose

  Itch Severity Scale (ISS, range 0-4; higher = worse itch)

  2 hours post second dose

• Change from baseline in in-clinic Hive Severity Scale at 2 hours post second dose

  Hive Severity Scale (HSS, range 0-4; higher = worse hive)

  2 hours post second dose

• Change from baseline in in-clinic Numeric Rating Scale at 2 hours post second dose

  Itch Numeric Rating Scale (NRS): from 0 (no itch) to 10 (worst imaginable itch)

  2 hours post second dose

• Proportion of participants with ≥1-point reduction from baseline in in-clinic Itch Severity Scale at 2 hours post second dose

  Itch Severity Scale (ISS, range 0-4; higher = worse itch)

  2 hours post second dose

• Proportion of participants with ≥1-point reduction from baseline in in-clinic Hive Severity Scale at 2 hours post second dose

  Hive Severity Scale (HSS, range 0-4; higher = worse hive)

  2 hours post second dose

• Proportion of participants with ≥3-point reduction from baseline in in-clinic Numeric Rating Scale at 2 hours post second dose (baseline clinic Numeric Rating Scale ≥3)

  Itch Numeric Rating Scale (NRS): from 0 (no itch) to 10 (worst imaginable itch)

  2 hours post second dose

• Proportion of participants with ≥4-point reduction from baseline in in-clinic Numeric Rating Scale at 2 hours post second dose (baseline clinic Numeric Rating Scale ≥4)

  Itch Numeric Rating Scale (NRS): from 0 (no itch) to 10 (worst imaginable itch)

  2 hours post second dose

Secondary Outcomes (7)

• Change from baseline in in-clinic Itch Severity Scale within 1 hour prior to third dose and at 2 hours post third dose

  Within 1 hour prior to third dose to 2 hours post third dose

• Change from baseline in in-clinic Hive Severity Scale within 1 hour prior to third dose and at 2 hours post third dose

  Within 1 hour prior to third dose to 2 hours post third dose

• Change from baseline in in-clinic Numeric Rating Scale within 1 hour prior to third dose and at 2 hours post third dose

  Within 1 hour prior to third dose to 2 hours post third dose

• Proportion of participants with ≥1-point reduction from baseline in in-clinic Itch Severity Scale within 1 hour prior to third dose and at 2 hours post third dose

  Within 1 hour prior to third dose to 2 hours post third dose

• Proportion of participants with ≥1-point reduction from baseline in in-clinic Hive Severity Scale within 1 hour prior to third dose and at 2 hours post third dose

  Within 1 hour prior to third dose to 2 hours post third dose

Other Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events

  From the first dosing to Day 3

Study Arms (3)

Arm 1

EXPERIMENTAL

TLL-018 10 mg

Drug: TLL-018; Drug: Placebo

Arm 2

EXPERIMENTAL

TLL-018 20 mg

Drug: TLL-018

Arm 3

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

TLL-018 DRUG

Participants will receive TLL-018 10 mg (1 tablet) and placebo (1 tablet) orally after meals, with a dosing interval of 12 hours (±15 minutes)

Arm 1

Placebo DRUG

Participants will receive placebo (2 tablets) orally after meals, with a dosing interval of 12 hours (±15 minutes)

Arm 1; Arm 3

Eligibility Criteria

• Age: 18 Years - 75 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 for ≥ 6 weeks prior to screening visit.
• UAS7 score (range 0-42) ≥ 16 and itch component of UAS7 (ISS range 0-21) ≥ 8 during 7 days prior to randomization (Day 1), and ISS ≥2 on the day of randomization.
• Participants are required to take a stable standard dose of a second generation H1-AH concomitantly according to local guidelines.
• Willing and able to to comply with the study protocol and complete the participant diary throughout the study period. Participants shall have no more than one missing urticaria symptom score (morning or evening HSS score and ISS score) within 7 days prior to randomization, and no missing HSS score or ISS score on the day immediately before randomization..
• Women of Child Bearing Potential (WOCBP) should not be pregnant or breastfeeding and the pregnancy test should be negative before randomization.
• Participants (whether male or female) should 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.

You may not qualify if:

• Participants who meet the diagnostic criteria for chronic spontaneous urticaria (CSU) shall be excluded if they present with any of the following conditions:
• Progressive or uncontrolled symptoms of renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiovascular, neurological, psychiatric or cerebral disorders that, in the investigator's judgment, would expose the patient to unacceptable risk from study participation.
• A well-defined underlying etiology of chronic urticaria other than CSU, such as inducible urticaria, including but not limited to dermatographism, cold contact urticaria, heat contact urticaria, delayed pressure urticaria, solar urticaria, vibratory angioedema, cholinergic urticaria, aquagenic urticaria, and contact urticaria.
• Other diseases presenting with urticaria or angioedema symptoms, including but not limited to urticarial vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary urticaria, drug-induced urticaria, and hereditary or acquired angioedema.
• Other chronic pruritic diseases that may interfere with efficacy outcome assessment, such as psoriasis, atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, and senile pruritus.
• History of any malignant neoplasm prior to screening, with the exception of non-melanoma skin cancer (NMSC) or basal cell carcinoma that has been adequately treated and deemed cured, cervical carcinoma in situ, or ductal carcinoma in situ of the breast.
• History of lymphoproliferative disorders (including but not limited to Epstein-Barr virus-related lymphoproliferative disorders, lymphoma, leukemia, etc.); or signs or symptoms suggestive of active lymphoproliferative disorder.
• History of cardiovascular or cerebrovascular events or related surgical procedures within 12 months prior to screening, including but not limited to myocardial infarction, unstable angina pectoris, acute coronary syndrome, cerebral hemorrhage, stroke, coronary artery stent implantation, percutaneous transluminal coronary angioplasty, and coronary artery bypass graft surgery.
• History of thromboembolic events within 12 months prior to screening (e.g., pulmonary thromboembolism, deep vein thrombosis, mesenteric artery embolism); or current high-risk factors for thromboembolic diseases (e.g., immobilization within 12 weeks prior to screening, congenital or hereditary thrombophilia, antiphospholipid antibody syndrome, etc.).
• History of gastrointestinal perforation, except for cases caused by appendicitis or trauma.
• History of herpes zoster within 1 year prior to randomization; history of disseminated herpes zoster or recurrent herpes zoster at any time prior to randomization; history of disseminated herpes simplex at any time prior to randomization.
• Positive HBsAg prior to randomization (or negative HBsAg with positive HBcAb and abnormal HBV-DNA test results), positive HCV antibody (with abnormal HCV-RNA test results), positive HIV antibody, or positive syphilis serological antibody; or known HIV infection or known immunodeficiency status.
• Any severe or systemic infection (bacterial, fungal, viral, parasitic, etc.) requiring intravenous antimicrobial therapy or resulting in hospitalization within 4 weeks prior to randomization; or any other active or recent infection that, in the investigator's judgment, would expose the participating patient to unacceptable risk.
• History of severe hematologic disorders (e.g., aplastic anemia, myelodysplastic syndrome) or any disease that may cause hemolysis or erythrocyte instability, such as malaria and hemolytic anemia.
• Participants with any of the following prior therapies or concomitant medications cannot be enrolled:

Sponsors & Collaborators

• Hangzhou Highlightll Pharmaceutical Co., Ltd: lead

Study Sites (1)

The Second People's Hospital of Chengdu

Chengdu, Sichuan, China

Location

MeSH Terms

Conditions

Chronic Urticaria

Condition Hierarchy (Ancestors)

Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Yanyan Feng, MD

CONTACT

86-13999163793; fyymed@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2026
• First Posted: June 24, 2026
• Study Start: July 15, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: July 1, 2026

Record last verified: 2026-06

Locations

CN (1)