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

NCT04827589 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: GS-US-556-59602020-005394-27
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) at Week 8.

  The UAS7 is the sum of the Hives Severity Score Over 7 Days (HSS7) and Itch Severity Score Over 7 Days (ISS7). The possible range of the UAS7 is 0 to 42. A well-controlled urticaria response is defined as a UAS7 ≤ 6. Higher scores indicate high disease activity in hives and itch. Hives Severity Score (HSS) is defined as the number of hives recorded twice daily by the participant on a scale from 0 (none) to 3 (severe). HSS7 is derived by adding together the daily average scores over a consecutive 7-day period. The severity of itch will be recorded twice daily by the participant using a scale from 0 (none) to 3 (severe). ISS7 is derived by adding together the daily average scores over a consecutive 7-day period.

  Baseline; Week 8

Secondary Outcomes (7)

• Change from baseline of Hives Severity Score Over 7 Days (HSS7) at Week 8

  Baseline; Week 8

• Change from baseline of Itch Severity Score Over 7 Days (ISS7) at Week 8

  Baseline; Week 8

• Proportion of Participants Achieving a Complete Response (UAS7 = 0) at Week 8

  Week 8

• Proportion of Participants Achieving Well-controlled Urticaria (UAS7 ≤ 6) at Week 8

  Week 8

• Change from Baseline in Angioedema Activity Score Over 7 Days (AAS7) at Week 8

  Baseline; Week 8

Study Arms (3)

Tirabrutinib

EXPERIMENTAL

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

Drug: Tirabrutinib

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Tirabrutinib, Open Label Extension

EXPERIMENTAL

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.

Drug: Tirabrutinib

Interventions

Tirabrutinib DRUG

Tablets administered orally

Also known as: GS-4059

Tirabrutinib; Tirabrutinib, Open Label Extension

Placebo DRUG

Tablets administered orally

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

MeSH Terms

Conditions

Chronic Urticaria

Interventions

tirabrutinib

Condition Hierarchy (Ancestors)

Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Study consists a placebo controlled period and an open label extension period. Sponsor is also masked for the placebo controlled period.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2021
• First Posted: April 1, 2021
• Study Start: July 1, 2021
• Primary Completion: April 1, 2022
• Study Completion: September 1, 2022
• Last Updated: July 28, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share