Study to Evaluate the Efficacy, Safety, and Tolerability of Tirabrutinib in Participants With Antihistamine-Resistant Chronic Spontaneous Urticaria

NCT ID: NCT04827589

Last Updated: 2021-07-28

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-31
• Study Completion Date: 2022-09-30

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.

Conditions

Chronic Spontaneous Urticaria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Tirabrutinib

Participant will receive tirabrutinib twice daily in addition to their standard-of-care therapy for up to 8 weeks.

Group Type: EXPERIMENTAL

Tirabrutinib

Intervention Type: DRUG

Tablets administered orally

Placebo

Participants will receive placebo twice daily in addition to their standard-of-care therapy for up to 8 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Tablets administered orally

Tirabrutinib, Open Label Extension

At Week 8, participants who have not discontinued the study drug will receive tirabrutinib twice daily in addition to their standard-of-care therapy for up to 16 weeks.

Group Type: EXPERIMENTAL

Tirabrutinib

Intervention Type: DRUG

Tablets administered orally

Interventions

Tirabrutinib

Tablets administered orally

Intervention Type: DRUG

Placebo

Tablets administered orally

Intervention Type: DRUG

Other Intervention Names

GS-4059

Eligibility Criteria

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).

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Other Identifiers

2020-005394-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-556-5960

Identifier Type: -

Identifier Source: org_study_id