Chronic Spontaneous Urticaria
Conditions
Brief summary
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.
Interventions
DRUGTacabrutideg
Administered orally
DRUGPlacebo
Administered orally
Sponsors
BeOne Medicines
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Part A is a double-blinded, placebo-controlled study to evaluate tacabrutideg in adults with moderate to severe CSU. Part B is an open-label study of tacabrutideg in healthy participants.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Number of participants with adverse events (AEs) | Up to approximately 4 months | Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including findings from laboratory tests and electrocardiogram results. |
| Part B: Number of participants with adverse events (AEs) | Up to approximately 6 weeks | Number of participants with TEAEs and SAEs, including findings from laboratory tests and electrocardiogram results. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| Part A: Change from Baseline in Weekly Urticaria Activity Score (UAS7) | Baseline and up to approximately 3 months | 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. |
| Part A: Change from baseline in weekly Itch Severity Score (ISS7) | Baseline and up to approximately 3 months | 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. |
| Part A: Change from baseline in weekly Hives Severity Score (HSS7) | Baseline and up to approximately 3 months | 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. |
| Part A: Change from baseline in weekly Angioedema Activity Score (AAS7) | Baseline and up to approximately 3 months | 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. |
| Part A: Change from baseline in 7-day recall period version of the Urticaria Control Test (UCT7) | Baseline and up to approximately 3 months | 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. |
| 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 | — |
Countries
China
Contacts
CONTACTStudy Director
STUDY_DIRECTORStudy Director
BeOne Medicines
Outcome results
None listed