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

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• Chronic Urticaria 213

Study arms

• Experimental
  Part A (CSU): Tacabrutideg

  Sequential cohorts of increasing dose levels of tacabrutideg will be evaluated in participants with CSU.

  Drug: Tacabrutideg

• Placebo comparator
  Part A (CSU): Placebo

  Participants with CSU will receive matching placebo orally for 28 days and then crossover to receive tacabrutideg.

  Drug: Tacabrutideg · Drug: Placebo

• Experimental
  Part B (Healthy Participants): Tacabrutideg

  Sequential cohorts of increasing dose levels of tacabrutideg will be evaluated in healthy participants.

  Drug: Tacabrutideg

Interventions

• DrugTacabrutideg

  Administered orally

  Also known as: BGB-16673

• DrugPlacebo

  Administered orally

Primary outcomes

1. 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.

   Time frame: Up to approximately 4 months

2. Part B: Number of participants with adverse events (AEs)

   Number of participants with TEAEs and SAEs, including findings from laboratory tests and electrocardiogram results.

   Time frame: Up to approximately 6 weeks

3. Part A: Maximum observed plasma concentration (Cmax) of tacabrutideg

   Time frame: Up to approximately 10 weeks

4. Part A: Minimum observed plasma concentration (Cmin) of tacabrutideg

   Time frame: Up to approximately 10 weeks

5. Part A: Time to reach maximum observed plasma concentration (Tmax) of tacabrutideg

   Time frame: Up to approximately 10 weeks

6. Part A: Apparent terminal elimination half life (t1/2) of tacabrutideg

   Time frame: Up to approximately 10 weeks

7. Part A: Area under the curve (AUC) of tacabrutideg

   Time frame: Up to approximately 10 weeks

8. Part A: Apparent oral clearance (CL/F) of tacabrutideg

   Time frame: Up to approximately 10 weeks

9. Part A: Apparent volume of distribution (Vz/F) of tacabrutideg

   Time frame: Up to approximately 10 weeks

10. Part A: Accumulation Ratio of AUC for tacabrutideg

    Time frame: Up to approximately 10 weeks

11. Part A: Accumulation Ratio of Cmax for tacabrutideg

    Time frame: Up to approximately 10 weeks

Secondary outcomes

1. 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.

   Time frame: Baseline and up to approximately 3 months

2. 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.

   Time frame: Baseline and up to approximately 3 months

3. 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.

   Time frame: Baseline and up to approximately 3 months

4. 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.

   Time frame: Baseline and up to approximately 3 months

5. 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.

   Time frame: Baseline and up to approximately 3 months

6. Part A: Percentage of participants with complete absence of hives and itch, assessed as UAS7 = 0

   Time frame: Up to approximately 3 months

7. Part A: Percentage of participants with UAS7 ≤ 6 response

   Time frame: Up to approximately 3 months

8. Part A: Levels of Bruton tyrosine kinase (BTK) protein

   Time frame: Up to approximately 3 months

Individual participant data

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Supporting information: Study protocol, Sap, Csr