Clinical trial NCT04827589: Study to Evaluate the Efficacy, Safety, and Tolerability of Tirabrutinib in Participants With Antihistamine-Resistant Chronic Spontaneous Urticaria
Official title: A Phase 2a, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy, Safety, and Tolerability of Tirabrutinib in Subjects With Antihistamine-Resistant Chronic Spontaneous Urticaria
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Chronic Spontaneous Urticaria
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2021-04-01
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the efficacy of tirabrutinib in reducing disease activity in participants with chronic spontaneous urticaria (CSU) with respect to change from baseline in urticaria activity score over 7 days (UAS7) at Week 8 when added to standard of care.


Eligibility criteria: Key Inclusion Criteria:

* Diagnosis of chronic spontaneous urticaria (CSU) (with or without urticarial dermatographism) for ≥ 6 months prior to screening
* Presence of itch and hives for ≥ 6 consecutive weeks prior to screening, refractory to nonsedating H1-antihistamines (according to local treatment guidelines) during that time
* Individuals must be maintained on approved H1-antihistamine doses as per the 2018 European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA2LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO) guidelines (2018 EAACI/GA2LEN/EDF/WAO; ie, up to 4 times standard dosing) from 7 days prior to randomization.
* Individuals must have active disease defined as UAS7 ≥ 16 and HSS7 ≥ 8 during the 7 consecutive days (with no missing timepoints) prior to randomization (Day -7 to Day -1).

Key Exclusion Criteria:

* Clearly defined underlying etiology for chronic urticaria other than CSU, including:

  * Inducible urticaria as the only manifestation of disease (cold, heat, pressure, delayed pressure, aquagenic, contact, cholinergic, dermatographism)
  * Known underlying genetic cause of urticaria or angioedema such as hereditary angioedema (C1-inhibitor deficiency)
  * Urticarial dermatoses associated with a known diagnosis of an autoinflammatory syndrome or monoclonal gammopathy
  * Diseases with possible urticarial manifestations such as urticarial vasculitis, erythema multiforme, or cutaneous mastocytosis
  * Any other skin disease associated with chronic itching that could confound the study evaluation (eg, atopic dermatitis, psoriasis, bullous pemphigoid, and dermatitis herpetiformis)
* Previous treatment with omalizumab or any other monoclonal antibody used to treat CSU within 16 weeks prior to randomization
* Refractory to omalizumab or biosimilar
* Previous use of a Bruton's tyrosine kinase (BTK) inhibitor
* Any prior history of anaphylaxis
* Use of a nonbiologic investigational drug or participation in an investigational study involving biologic therapy within 90 days or 5 half-lives (whichever is greater) prior to randomization
* Intravenous immunoglobulin (IVIg) or plasmapheresis within 28 days prior to randomization
* Use of cyclosporine A, methotrexate, mycophenolate mofetil (or mycophenolic acid), or azathioprine within 28 days prior to randomization; or use of dupilumab within 16 weeks prior to randomization
* Routine (daily or every other day use for 5 or more consecutive days) of systemic corticosteroids within 28 days of randomization
* Use of intramuscular corticosteroids within 28 days of randomization
* Any clinically unstable disease states that would likely require rescue corticosteroids (eg, severe asthma) that may interfere with data interpretation

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

Primary outcomes:
measure: Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) at Week 8.
timeFrame: Baseline; Week 8
Secondary outcomes:
measure: Change from baseline of Hives Severity Score Over 7 Days (HSS7) at Week 8
timeFrame: Baseline; Week 8
measure: Change from baseline of Itch Severity Score Over 7 Days (ISS7) at Week 8
timeFrame: Baseline; Week 8
measure: Proportion of Participants Achieving a Complete Response (UAS7 = 0) at Week 8
timeFrame: Week 8
measure: Proportion of Participants Achieving Well-controlled Urticaria (UAS7 ≤ 6) at Week 8
timeFrame: Week 8
measure: Change from Baseline in Angioedema Activity Score Over 7 Days (AAS7) at Week 8
timeFrame: Baseline; Week 8
measure: Proportion of Participants Achieving a Complete Angioedema Response (AAS7 = 0) at Week 8
timeFrame: Week 8
measure: Change From Baseline in the Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) Measurement at Week 8
timeFrame: Baseline; Week 8
Other outcomes:
Locations:
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: