A Study of GDC-0853 in Participants With Refractory Chronic Spontaneous Urticaria (CSU).
Condition: Urticaria
MeSH terms: Urticaria; Chronic Urticaria
Intervention: GDC-0853; Placebo
Intervention description: GDC-0853 will be administered orally at dosages of 50, 150 and 200mg to participants, as per the dosing schedules described above.; Matching Placebo will be administered orally, as per the dosing schedules described above.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 134.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the efficacy, safety and pharmacokinetics of
      GDC-0853 compared with placebo in participants with Refractory Chronic Spontaneous Urticaria
      (CSU) already treated with anti-histamines. Participants have the option to enter the
      Open-Label Extension (OLE) study after completing the 8-week treatment period.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Aged 18-75 years, inclusive

          -  Diagnosis of chronic spontaneous urticaria (CSU) refractory to H1 antihistamines at
             the time of randomization

          -  Willing and able to complete an Urticaria Participant Daily eDiary for the duration of
             the study

          -  No evidence of active or latent or inadequately treated infection with tuberculosis
             (TB)

          -  Partcipants with a history of Bacille Calmette-Guérin (BCG) vaccination should be
             screened using the QuantiFERON-TB-Gold (QFT) test

          -  Only for participants currently receiving proton-pump inhibitors (PPIs) or H2 receptor
             antagonists (H2RAs): Treatment must be at a stable dose during the 2-week screening
             period prior to randomization and with a plan to remain at a stable dose for the
             duration of the study

          -  For women of childbearing potential: Agreement to remain abstinent (refrain from
             heterosexual intercourse) or use contraceptive methods that result in a failure rate
             of <1% per year during the treatment period and for at least 4 weeks after the last
             dose of study drug. Women must refrain from donating eggs during this same period.

        Exclusion Criteria:

          -  Treatment with omalizumab or other monoclonal antibody therapies used to treat CSU
             within 4 months prior to screening or primary nonresponse to omalizumab

          -  Use of a non-biologic investigational drug or participation in an investigational
             study with a non-biologic drug within 30 days prior to study drug administration on
             Day 1 (or within 5 half-lives of the investigational product, whichever is greater)

          -  Use of a biologic investigational therapy or participation in an investigational study
             involving biologic therapy within 90 days or 5 half-lives, whichever is greater, prior
             to study drug administration on Day 1

          -  Previous treatment with GDC-0853 or other Bruton's tyrosine kinase (BTK) inhibitors

          -  Participants whose urticaria is solely due to physical urticaria

          -  Other diseases with symptoms of urticaria or angioedema, including urticarial
             vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary or
             acquired angioedema, lymphoma, or leukemia

          -  Atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, or other skin disease
             associated with itch such as psoriasis

          -  Routine doses of the following medications within 30 days prior to screening: systemic
             or cutaneous (topical) corticosteroids (prescription or over the counter),
             hydroxychloroquine, methotrexate, cyclosporine, or cyclophosphamide

          -  Prior utilization of intravenous (IV) steroids for treatment of laryngeal angioedema

          -  Intravenous immunoglobulin G (IV IG) or plasmapheresis within 30 days prior to
             screening

          -  History of anaphylactic shock without clearly identifiable avoidable antigen

          -  Hypersensitivity to GDC-0853 or any component of the formulation

          -  Major surgery within 8 weeks prior to screening or surgery planned prior to end of
             study (12 weeks after randomization)

          -  Require any prohibited concomitant medications

          -  History of live attenuated vaccine within 6 weeks prior to randomization or
             requirement to receive these vaccinations at any time during study drug treatment

          -  Evidence of clinically significant cardiac, neurologic, psychiatric, pulmonary, renal,
             hepatic, endocrine, metabolic, or gastrointestinal (GI) disease that, in the
             investigator's opinion, would compromise the safety of the participant, interfere with
             the interpretation of the study results or otherwise preclude participant
             participation

          -  Current treatment with astemizole, terfenadine, and/or ebastine

          -  Uncontrolled disease states, such as asthma, psoriasis, or inflammatory bowel disease,
             where flares are commonly treated with oral or parenteral corticosteroids