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
Overview
- Phase
- Phase 3
- Intervention
- TLL-018 tablets
- Conditions
- Chronic Spontaneous Urticaria
- Sponsor
- Hangzhou Highlightll Pharmaceutical Co., Ltd
- Enrollment
- 436
- Locations
- 1
- Primary Endpoint
- Change from baseline in UAS7 at Week 12
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
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.
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Aged between 18 and
- •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:
- •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 judgment of efficacy results, such as psoriasis, atopic dermatitis, etc.
- •Previous malignancy, herpes zoster, active tuberculosis.
- •Other symptoms of progressive or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiovascular, neurological, psychiatric, or cerebral disease.
- •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:
- •Have received any study drug within 4 weeks or less than 5 elimination of half-life period before randomization (whichever is longer).
- •Have received biological agent within 3 months or 5 elimination of half-life period prior to randomization (whichever is longer).
Arms & Interventions
Arm 1
TLL018 tablets,1piece,BID
Intervention: TLL-018 tablets
Arm 2
Placebo tablets,1piece,BID
Intervention: Placebo tablets
Outcomes
Primary Outcomes
Change from baseline in UAS7 at Week 12
Time Frame: 12 weeks
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.
Change from baseline in ISS7 at Week 12
Time Frame: 12 weeks
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.
Secondary Outcomes
- Change from baseline in HSS7 at Week 12(12 weeks)
- Proportion of Participants With UAS7≤6 Response at Week 12(12 weeks)
- Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events(52 weeks)
- Proportion of Participants With UAS7=0 Response at Week 12(12 weeks)
- Change from baseline in DLQI at Week 12(12 weeks)
- Proportion of Participants With DLQI=0/1 Response at Week 12(12 weeks)