Chronic Spontaneous UrticariaPhase 2NCT04827589
Study to Evaluate the Efficacy, Safety, and Tolerability of Tirabrutinib in Participants With Antihistamine-Resistant Chronic Spontaneous Urticaria
A Phase 2 study testing Tirabrutinib in people with Chronic Spontaneous Urticaria, run by Gilead Sciences.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Chronic Spontaneous Urticaria
- What is being tested?
- Tirabrutinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jul 2021to Sep 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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)
Show all 17Show fewer
- 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.
About this study
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
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
- Being tested
- Tirabrutinib, Placebo
- Medical subject headings
- Chronic Urticaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TirabrutinibDrug
Also called GS-4059
Tablets administered orally
PlaceboDrug
Tablets administered orally
| Study group | Role | What they receive |
|---|---|---|
| Tirabrutinib | Experimental | Participant will receive tirabrutinib twice daily in addition to their standard-of-care therapy for up to 8 weeks. Receives: Drug: Tirabrutinib |
| Placebo | Placebo comparator | Participants will receive placebo twice daily in addition to their standard-of-care therapy for up to 8 weeks. Receives: 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. Receives: Drug: Tirabrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline; Week 8
Secondary outcomes (7)
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.
Measured: Baseline; Week 8
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.
Measured: Baseline; Week 8
Proportion of Participants Achieving a Complete Response (UAS7 = 0) at Week 8
Measured: Week 8
Proportion of Participants Achieving Well-controlled Urticaria (UAS7 ≤ 6) at Week 8
Measured: 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.
Measured: Baseline; Week 8
Proportion of Participants Achieving a Complete Angioedema Response (AAS7 = 0) at Week 8
Measured: 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.
Measured: Baseline; Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2021
- Study startJul 2021 (estimated)
- Primary completionApr 2022 (estimated)
- Study completionSep 2022 (estimated)
Why it stopped: Development program terminated
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Spontaneous UrticariaStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gilead Study Director, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04827589
- Sponsor's protocol ID
- GS-US-556-5960
- Other IDs
- 2020-005394-27
- Status last verified
- Jul 2021
- First submitted
- 30 Mar 2021
- Last updated
- 28 Jul 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04827589
- Acronym / sponsor ID
- GS-US-556-5960
- Conditions
- Chronic Spontaneous Urticaria
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Development program terminated
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- Jul 2021 (estimated)
- Primary completion
- Apr 2022 (estimated)
- Study completion
- Sep 2022 (estimated)
- First posted
- 1 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Tirabrutinib | Experimental | Drug: TirabrutinibParticipant will receive tirabrutinib twice daily in addition to their standard-of-care therapy for up to 8 weeks. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants will receive placebo twice daily in addition to their standard-of-care therapy for up to 8 weeks. |
| Tirabrutinib, Open Label Extension | Experimental | Drug: TirabrutinibAt 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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 (17 listed)
- Clearly defined underlying etiology for chronic urticaria other than CSU, including:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TirabrutinibAlso: GS-4059Tablets administered orally | Drug | Tirabrutinib, Tirabrutinib, Open Label Extension |
| PlaceboTablets administered orally | Drug | Placebo |
Primary outcome
Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) at Week 8.
Time frame: Baseline; 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.
7 secondary outcomes
Change from baseline of Hives Severity Score Over 7 Days (HSS7) at Week 8
Time frame: Baseline; Week 8
Change from baseline of Itch Severity Score Over 7 Days (ISS7) at Week 8
Time frame: Baseline; Week 8
Proportion of Participants Achieving a Complete Response (UAS7 = 0) at Week 8
Time frame: Week 8
Proportion of Participants Achieving Well-controlled Urticaria (UAS7 ≤ 6) at Week 8
Time frame: Week 8
Change from Baseline in Angioedema Activity Score Over 7 Days (AAS7) at Week 8
Time frame: Baseline; Week 8
Proportion of Participants Achieving a Complete Angioedema Response (AAS7 = 0) at Week 8
Time frame: Week 8
Change From Baseline in the Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) Measurement at Week 8
Time frame: Baseline; Week 8
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gilead Study Director study director
Gilead Sciences
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tirabrutinib in people with Chronic Spontaneous Urticaria, run by Gilead Sciences.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 28 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) at Week 8. (time frame: Baseline; Week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2021; AzTrials last refreshed its copy on 8 Nov 2026.