A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple-Ascending Doses of Tacabrutideg (BGB-16673) in Adults With Chronic Spontaneous Urticaria and in Healthy Participants

A Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple- Ascending Doses of BGB-16673 in Patients With Chronic Spontaneous Urticaria and in Healthy Participants

This is a Phase 1b study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of multiple-ascending doses of tacabrutideg in adults with chronic spontaneous urticaria (CSU) and in healthy participants.

Study Overview

• Status: Recruiting
• Conditions: Chronic Spontaneous Urticaria
• Intervention / Treatment: Drug: Placebo; Drug: Tacabrutideg

• Study Type: Interventional
• Enrollment (Estimated): 58
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Study Director; Phone Number: 1-877-828-5568; Email: clinicaltrials@beonemed.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100000
      • Completed
      • Peking University Third Hospital
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 630014
      • Completed
      • The First Affiliated Hospital of Chongqing Medical University
  • Guangdong
    • Guangzhou, Guangdong, China
      • Completed
      • Dermatology Hospital of Southern Medical University
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Completed
      • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
  • Hunan
    • Changsha, Hunan, China, 410008
      • Completed
      • Xiangya Hospital of Central South University
  • Shandong
    • Qingdao, Shandong, China, 266555
      • Recruiting
      • The Affiliated Hospital of Qingdao University Branch West Coast
  • Sichuan
    • Chengdu, Sichuan, China, 610021
      • Completed
      • Chengdu Second Peoples Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310006
      • Completed
      • Hangzhou First Peoples Hospital
    • Wenzhou, Zhejiang, China, 325000
      • Completed
      • The First Affiliated Hospital of Wenzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Part A

• Participants must be diagnosed with chronic spontaneous urticaria (CSU) for ≥ 6 months before randomization.
• The presence of itch and hives for ≥6 consecutive weeks at any time prior to randomization despite the use of second-generation H1-antihistamines
• UAS7≥16 and HSS7≥8 during the 7 days before randomization
• Participants must not have had any missing UAS7 entry (ISS7 and HSS7) during the 7 days before randomization
• Presence of hives must have been documented within 3 months before randomization

Part B

• Participants must be 18 to 55 years of age and healthy, with no clinically relevant abnormalities.
• Body Mass Index (BMI) of 18 to 32 kg/m^2; and a total body weight > 50 kg (110 lbs).

Exclusion Criteria:

Part A

• Participants who have a clearly defined, predominating or sole trigger for their chronic urticaria (chronic inducible urticaria), including urticaria factitia (symptomatic dermographism) or cold, heat, solar, pressure, delayed pressure, aquagenic, cholinergic, or contact urticaria.
• Other diseases with symptoms of urticaria or angioedema
• Any other skin disease associated with chronic itching that might influence in the investigators opinion the study evaluations and results, eg, atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, or psoriasis.

All Participants

• Any uncontrolled disease state, including asthma or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids.
• Significant bleeding risk or coagulopathy.
• Prior exposure to any BTK inhibitors or protein degraders.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A (CSU): Tacabrutideg; Sequential cohorts of increasing dose levels of tacabrutideg will be evaluated in participants with CSU.	Drug: Tacabrutideg; Administered orally; Other Names: BGB-16673
Placebo Comparator: Part A (CSU): Placebo; Participants with CSU will receive matching placebo orally for 28 days and then crossover to receive tacabrutideg.	Drug: Placebo; Administered orally; Drug: Tacabrutideg; Administered orally; Other Names: BGB-16673
Experimental: Part B (Healthy Participants): Tacabrutideg; Sequential cohorts of increasing dose levels of tacabrutideg will be evaluated in healthy participants.	Drug: Tacabrutideg; Administered orally; Other Names: BGB-16673

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Number of participants with adverse events (AEs)	Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including findings from laboratory tests and electrocardiogram results.	Up to approximately 4 months
Part B: Number of participants with adverse events (AEs)	Number of participants with TEAEs and SAEs, including findings from laboratory tests and electrocardiogram results.	Up to approximately 6 weeks
Part A: Maximum observed plasma concentration (Cmax) of tacabrutideg		Up to approximately 10 weeks
Part A: Minimum observed plasma concentration (Cmin) of tacabrutideg		Up to approximately 10 weeks
Part A: Time to reach maximum observed plasma concentration (Tmax) of tacabrutideg		Up to approximately 10 weeks
Part A: Apparent terminal elimination half life (t1/2) of tacabrutideg		Up to approximately 10 weeks
Part A: Area under the curve (AUC) of tacabrutideg		Up to approximately 10 weeks
Part A: Apparent oral clearance (CL/F) of tacabrutideg		Up to approximately 10 weeks
Part A: Apparent volume of distribution (Vz/F) of tacabrutideg		Up to approximately 10 weeks
Part A: Accumulation Ratio of AUC for tacabrutideg		Up to approximately 10 weeks
Part A: Accumulation Ratio of Cmax for tacabrutideg		Up to approximately 10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Change from Baseline in Weekly Urticaria Activity Score (UAS7)	The UAS7 consists of an assessment of both hives and itch severity to provide a measure of disease activity. The UAS7 is the sum of the weekly Hives Severity Score (HSS7) and the weekly Itch Severity Score (ISS7) and ranges between 0 and 42. A UAS7 score of 0 signifies that the patient is symptom free, and high UAS7 scores indicate severe symptoms.	Baseline and up to approximately 3 months
Part A: Change from baseline in weekly Itch Severity Score (ISS7)	The Itch Severity Score (ISS) is a measure of itching. Daily scores range from 0 (no itching) to 3 (intense itching). The ISS7 is a weekly score derived by adding up the daily ISS scores of the past 7 days and ranges from 0 to 21.	Baseline and up to approximately 3 months
Part A: Change from baseline in weekly Hives Severity Score (HSS7)	The Hives Severity Score (HSS) is a measure of the number of hives present recorded by the participant. Daily scores range from 0 (no hives) to 3 (intense/severe hives). HSS7 is the sum of the daily HSS scores over the past 7 days and ranges from 0 to 21.	Baseline and up to approximately 3 months
Part A: Change from baseline in weekly Angioedema Activity Score (AAS7)	The Angioedema Activity Score (AAS) is a validated tool designed and verified to measure disease activity, assess response to treatment, and optimize the treatment plan for patients with recurrent angioedema. Responses are filled out prospectively and daily, evaluating five main factors related to angioedema: duration, physical discomfort caused, impact on daily activities, effect on appearance, and overall severity, each scored between 0 and 3. Daily AAS scores can range daily from 0 to 15, and weekly (AAS7) from 0 to 105. Higher AAS scores indicate frequent and severe attacks. Lower scores indicate well-controlled symptoms.	Baseline and up to approximately 3 months
Part A: Change from baseline in 7-day recall period version of the Urticaria Control Test (UCT7)	UCT7 is a validated questionnaire used to measure the quality of life of patients with chronic urticaria and angioedema. It contains 4 questions, each of which inquires about the extent of impairment in the previous 7 days, with 5 options for answers ranging from "not at all" to "very much." The first question asks about the frequency of all symptoms combined (itching, hives, and/or swelling). The second question asks about the overall impact on quality of life. The third question asks how often treatment has been insufficient to control symptoms, and the final question asks about how well the disease has been controlled. Answers are scored from 0 to 4 (the total score will range from 0 to 16), with higher scores representing milder and better-controlled urticaria and angioedema. The recall period for this questionnaire is 7 days.	Baseline and up to approximately 3 months
Part A: Percentage of participants with complete absence of hives and itch, assessed as UAS7 = 0		Up to approximately 3 months
Part A: Percentage of participants with UAS7 ≤ 6 response		Up to approximately 3 months
Part A: Levels of Bruton tyrosine kinase (BTK) protein		Up to approximately 3 months

Collaborators and Investigators

• Sponsor: BeOne Medicines
• Investigators: Study Director: Study Director, BeOne Medicines

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2025
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: May 22, 2025
• First Submitted That Met QC Criteria: June 3, 2025
• First Posted (Actual): June 5, 2025

Study Record Updates

• Last Update Posted (Actual): September 9, 2026
• Last Update Submitted That Met QC Criteria: September 3, 2026
• Last Verified: September 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; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: BGB-16673-107

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

BeOne shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved.

BeOne shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.

Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeOne review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

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