Back to resultsStudy to Evaluate the Efficacy, Safety, and Tolerability of Tirabrutinib in Participants With Antihistamine-Resistant Chronic Spontaneous Urticaria
Primary Purpose
Chronic Spontaneous Urticaria
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Tirabrutinib
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Spontaneous Urticaria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Placebo Comparator
Experimental
Arm Label
Tirabrutinib
Placebo
Tirabrutinib, Open Label Extension
Arm Description
Participant will receive tirabrutinib twice daily in addition to their standard-of-care therapy for up to 8 weeks.
Participants will receive placebo twice daily in addition to their standard-of-care therapy for up to 8 weeks.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Change from baseline of Hives Severity Score Over 7 Days (HSS7) at Week 8
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 range of weekly scores is 0 to 21. Higher scores indicate increase severity in hives.
Change from baseline of Itch Severity Score Over 7 Days (ISS7) at Week 8
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. The range of weekly scores is 0 to 21. Higher scores indicate increase severity in itch.
Proportion of Participants Achieving a Complete Response (UAS7 = 0) at Week 8
Proportion of Participants Achieving Well-controlled Urticaria (UAS7 ≤ 6) at Week 8
Change from Baseline in Angioedema Activity Score Over 7 Days (AAS7) at Week 8
The Angioedema Activity Score (AAS) assesses the occurrence of episodes of angioedema. The AAS will be recorded by the participant once daily. A weekly score (AAS7) is derived by adding together the daily scores over a consecutive 7-day period. The range of weekly scores is 0 to 105, with a higher score corresponding to greater severity.
Proportion of Participants Achieving a Complete Angioedema Response (AAS7 = 0) at Week 8
Change From Baseline in the Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) Measurement at Week 8
The CU-Q2oL is a 23-item questionnaire. Domains in the questionnaire include urticaria- and angioedema-specific symptoms, discomfort, sleep, mood and activities of daily living. Each response is scored from 1 (no symptoms) to 5 (severe symptoms). Individual responses are summed to produce the overall CU-Q2oL score, which is then converted to a 0 to 100-point scale. A higher score indicates greater impairment in quality of life.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04827589
Brief Title
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
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Withdrawn
Why Stopped
Development program terminated
Study Start Date
July 2021 (Anticipated)
Primary Completion Date
April 2022 (Anticipated)
Study Completion Date
September 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Spontaneous Urticaria
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Masking Description
Study consists a placebo controlled period and an open label extension period. Sponsor is also masked for the placebo controlled period.
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tirabrutinib
Arm Type
Experimental
Arm Description
Participant will receive tirabrutinib twice daily in addition to their standard-of-care therapy for up to 8 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive placebo twice daily in addition to their standard-of-care therapy for up to 8 weeks.
Arm Title
Tirabrutinib, Open Label Extension
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Tirabrutinib
Other Intervention Name(s)
GS-4059
Intervention Description
Tablets administered orally
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Tablets administered orally
Primary Outcome Measure Information:
Title
Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) at Week 8.
Description
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.
Time Frame
Baseline; Week 8
Secondary Outcome Measure Information:
Title
Change from baseline of Hives Severity Score Over 7 Days (HSS7) at Week 8
Description
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 range of weekly scores is 0 to 21. Higher scores indicate increase severity in hives.
Time Frame
Baseline; Week 8
Title
Change from baseline of Itch Severity Score Over 7 Days (ISS7) at Week 8
Description
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. The range of weekly scores is 0 to 21. Higher scores indicate increase severity in itch.
Time Frame
Baseline; Week 8
Title
Proportion of Participants Achieving a Complete Response (UAS7 = 0) at Week 8
Time Frame
Week 8
Title
Proportion of Participants Achieving Well-controlled Urticaria (UAS7 ≤ 6) at Week 8
Time Frame
Week 8
Title
Change from Baseline in Angioedema Activity Score Over 7 Days (AAS7) at Week 8
Description
The Angioedema Activity Score (AAS) assesses the occurrence of episodes of angioedema. The AAS will be recorded by the participant once daily. A weekly score (AAS7) is derived by adding together the daily scores over a consecutive 7-day period. The range of weekly scores is 0 to 105, with a higher score corresponding to greater severity.
Time Frame
Baseline; Week 8
Title
Proportion of Participants Achieving a Complete Angioedema Response (AAS7 = 0) at Week 8
Time Frame
Week 8
Title
Change From Baseline in the Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) Measurement at Week 8
Description
The CU-Q2oL is a 23-item questionnaire. Domains in the questionnaire include urticaria- and angioedema-specific symptoms, discomfort, sleep, mood and activities of daily living. Each response is scored from 1 (no symptoms) to 5 (severe symptoms). Individual responses are summed to produce the overall CU-Q2oL score, which is then converted to a 0 to 100-point scale. A higher score indicates greater impairment in quality of life.
Time Frame
Baseline; Week 8
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study to Evaluate the Efficacy, Safety, and Tolerability of Tirabrutinib in Participants With Antihistamine-Resistant Chronic Spontaneous Urticaria
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