A Study of Efficacy and Safety of TLL-018 in CSU Participants

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of TLL-018 in Participants With Moderate-to-Severe Chronic Spontaneous Urticaria With Inadequate Controll to Second Generation H1-antihistamines

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of TLL-018 in Participants With Moderate-to-Severe Chronic Spontaneous Urticaria (CSU) With Inadequate Controll to Second Generation H1-antihistamines.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Spontaneous Urticaria
• Intervention / Treatment: Drug: TLL-018 tablets; Drug: Placebo tablets

Detailed Description

This is a randomized, double-blind, single-dummy, placebo-parallel-group, phase 3 study to assess the safety and efficacy of TLL-018 in Moderate-to-Severe Chronic Spontaneous Urticaria (CSU) participants who had an Inadequate Controll to Second Generation H1-antihistamines.

• Study Type: Interventional
• Enrollment (Actual): 440
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged between 18 and 75.
• Diagnosis of CSU refractory to secomd-generation H1-AH.
• CSU diagnosis for ≥ 6 months.
• The presence of itch and hivese despite current use of an approved dose of H1-AH prior to screening visit.
• UAS7 score (range 0-42) ≥ 16 and itch component of UAS7 (range 0-21) ≥ 8 during 7 days prior to randomization (Day 1).
• 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 for the duration of the study.
• 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 (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.

Exclusion Criteria:

• Participants meeting Chinese Guidelines for Urticaria Diagnosis and Treatment with the following concomitant diseases cannot be enrolled:

  1. Clearly defined underlying etiology for chronic urticarias other than CSU. E.g. induced urticaria, including but not limited to artificial urticaria.
  2. Any disease, which may have symptoms of urticaria and/or angioedema, including but not limited to urticaria and vasculitis.
  3. Suffering from other chronic pruritic diseases that may affect the judgment of efficacy results, such as psoriasis, atopic dermatitis, etc.
  4. Previous malignancy, herpes zoster, active tuberculosis.
  5. Other symptoms of progressive or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiovascular, neurological, psychiatric, or cerebral disease.
  6. Taking part in this study, in the opinion of the investigator, places the patient at unacceptable risk.

• Participants with any of the following prior therapies or concomitant medications cannot be enrolled:

  1. Have received any study drug within 4 weeks or less than 5 elimination of half-life period before randomization (whichever is longer).
  2. Have received biological agent within 3 months or 5 elimination of half-life period prior to randomization (whichever is longer).
  3. Have received immunosuppressive/modulatory drug within 4 weeks before randomization.
  4. Have received any live vaccine within 2 months before randomization or plan to receive a live vaccine during the study.
• Have experienced major surgery within 4 weeks before randomization, or expected to receive major surgical treatment after enrollment;
• Have donated blood more than 400 ml or received blood transfusion within 3 months prior to the study.
• History of drug or alcohol abuse within 6 months prior to screening.
• Allergy to ingredients or excipients of H1-AH or TLL-018.
• Laboratory test results are abnormal and may interfere the study judged by investigators.
• Participants are not appropriate for participation in any other situation or condition in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; TLL018 tablets,1 tablet ,BID	Drug: TLL-018 tablets; Oral TLL-018 tablets taken orally 1 pieces BlD for 52 weeks
Placebo Comparator: Arm 2; Placebo tablets, 1 tablet ,BID	Drug: Placebo tablets; Oral Placebo tablets taken orally 1 pieces BlD for 12 weeks and then Oral TLL-018 tablets taken orally 1 pieces BlD for 40 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in UAS7 at Week 12	To demonstrate that TLL-018 is superior to placebo in CSU with respect to change from baseline in UAS7 at Week 12 by assessing absolute change from baseline in weekly Urticaria Activity Score (UAS7) at week 12. The 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.	12 weeks
Change from baseline in ISS7 at Week 12	To demonstrate that TLL-018 is superior to placebo in CSU with respect to change from baseline in ISS7 at Week 12 by assessing absolute change from baseline in weekly Itch Severity Score (ISS7) at week 12. The ISS7 is the itch severity score for 7 days, and it ranges from 0 to 21.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in HSS7 at Week 12	To demonstrate that TLL-018 is superior to placebo in CSU with respect to change from baseline in HSS7 at Week 12 by assessing absolute change from baseline in hive severity score (HSS7) at week 12. The HSS7 is the hive severity score for 7 days, and it ranges from 0 to 21.	12 weeks
Proportion of Participants With UAS7≤6 Response at Week 12	To demonstrate that a greater proportion of participants achieve disease activity control UAS7≤6 at Week 12 who are treated with TLL-018 compared to placebo-treated participants by assessing achievement of UAS7≤6 at week 12.	12 weeks
Proportion of Participants With UAS7=0 Response at Week 12	To demonstrate that a greater proportion of participants achieve complete absence of hives and itch (UAS7 = 0) at Week 12 who are treated with TLL-018 compared to placebo-treated participants by achievement of UAS7 = 0 at week 12.	12 weeks
Proportion of Participants With DLQI=0/1 Response at Week 12	To demonstrate that a greater proportion of participants who are treated with TLL-018 achieve DLQI = 0/1 at Week 12 compared to placebo-treated participants by assessing achievement of DLQI = 0/1 at week 12.	12 weeks
Change from baseline in DLQI at Week 12	To demonstrate that TLL-018 is superior to placebo in CSU with respect to change from baseline in DLQI at Week 12 by assessing absolute change from baseline in DLQI at week 12.	12 weeks
Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events	To demonstrate the safety and tolerability of TLL-018 by assessing occurrence of treatment emergent adverse events and serious adverse events during the study.	52 weeks

Collaborators and Investigators

• Sponsor: Hangzhou Highlightll Pharmaceutical Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2024
• Primary Completion (Actual): October 23, 2025
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: April 29, 2024
• First Submitted That Met QC Criteria: April 29, 2024
• First Posted (Actual): May 2, 2024

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Skin Diseases; Urticaria; Skin Diseases, Vascular; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Chronic Urticaria
• Other Study ID Numbers: TLL-018-303

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No