Clinical trial NCT06396026: A Study of Efficacy and Safety of TLL-018 in CSU Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Chronic Spontaneous Urticaria
Lead sponsor: Hangzhou Highlightll Pharmaceutical Co., Ltd
Sponsor class: INDUSTRY
First posted: 2024-05-02
Enrollment: 436
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Drug: TLL-018 Drug: Placebo
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline in UAS7 at Week 12
timeFrame: 12 weeks
measure: Change from baseline in ISS7 at Week 12
timeFrame: 12 weeks
Secondary outcomes:
measure: Change from baseline in HSS7 at Week 12
timeFrame: 12 weeks
measure: Proportion of Participants With UAS7≤6 Response at Week 12
timeFrame: 12 weeks
measure: Proportion of Participants With UAS7=0 Response at Week 12
timeFrame: 12 weeks
measure: Proportion of Participants With DLQI=0/1 Response at Week 12
timeFrame: 12 weeks
measure: Change from baseline in DLQI at Week 12
timeFrame: 12 weeks
measure: Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences
state: Jiangsu
Study officials:
References: