A Study of GDC-0853 in Participants With Refractory Chronic Spontaneous Urticaria (CSU).

Phase 2

Completed

Conditions: Urticaria

Interventions: Drug: Placebo
Drug: GDC-0853

Registration Number: NCT03137069

Lead Sponsor: Genentech, Inc.

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 134

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1: Placebo	Placebo	Participants received matching placebo twice daily from Day 1 to 56.
Cohort 1: GDC-0853 200mg BID	GDC-0853	Participants received GDC-0853 200mg twice daily from Day 1 to 56.
Cohort 2: Placebo	Placebo	Participants received matching placebo up to twice daily from Day 1 to 56.
Cohort 2: GDC-0853 50mg QD	GDC-0853	Participants received GDC-0853 50mg once daily from Day 1 to 56.
Cohort 2: GDC-0853 150mg QD	GDC-0853	Participants received GDC-0853 150mg once daily from Day 1 to 56.
Cohort 2: GDC-0853 200mg BID	GDC-0853	Participants received GDC-0853 200mg twice daily from Day 1 to 56.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in the Urticaria Activity Score Over 7 Days (UAS7) at Day 57	Baseline and Day 57	The Urticaria Activity Score (UAS) is a composite, diary-recorded score with numeric severity intensity ratings (0=none to 3=intense/severe) for the number of wheals (hives) and the intensity of the pruritus (itch) over the past 12 hours (twice daily). The daily UAS is calculated as the average of the morning and evening scores. The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. The maximum UAS7 value is 42. A higher score indicates worse disease. A negative change score (Day 57 score minus Baseline score) indicates improvement.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in the UAS7 at Day 29	Baseline and Day 29	The Urticaria Activity Score (UAS) is a composite, diary-recorded score with numeric severity intensity ratings (0=none to 3=intense/severe) for the number of wheals (hives) and the intensity of the pruritus (itch) over the past 12 hours (twice daily). The daily UAS is calculated as the average of the morning and evening scores. The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. The maximum UAS7 value is 42. A higher score indicates worse disease. A negative change score (Day 29 score minus Baseline score) indicates improvement.
Plasma Concentrations of Fenebrutinib (GDC-0853) at Specified Timepoints	Days 1, 8 and 57.	Plasma Concentration Data for fenebrutinib (GDC-0853) will be tabulated and summarised by visits. Descriptive summary statistics for Arithmetic Mean and Standard Deviation will be presented. Please note that the Placebo Cohorts were not evaluated for this Outcome Measure.
Percentage of Participants With Adverse Events (AEs)	Baseline up until 4 weeks after the last dose of study drug (up to 2 years, 5 months).	An Adverse Event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An Adverse Event can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as Adverse Events.
Percentage of Participants Who Are Well-Controlled (UAS7 ≤ 6)	Day 57	The Urticaria Activity Score (UAS) is a composite, diary-recorded score with numeric severity intensity ratings (0=none to 3=intense/severe) for the number of wheals (hives) and the intensity of the pruritus (itch) over the past 12 hours (twice daily). The daily UAS is calculated as the average of the morning and evening scores. The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. The maximum UAS7 value is 42. A higher score indicates worse disease. Participants with UAS7 score ≤6 are considered well controlled.

Trial Locations

Locations (27): Gordon Sussman Clinical Research
🇨🇦
Toronto, Ontario, Canada
New Horizon Research Center
🇺🇸
Miami, Florida, United States
Universitätsmedizin Johannes Gutenberg Universität
🇩🇪
Mainz, Germany
Allergy & Asthma Immunology Associates
🇺🇸
Scottsdale, Arizona, United States
Clinical Research Center of Alabama, LLC
🇺🇸
Birmingham, Alabama, United States
Kern Allergy Med Clinic, Inc.
🇺🇸
Bakersfield, California, United States
Integrated Research Group Inc
🇺🇸
Riverside, California, United States
Allergy & Asthma Consultants
🇺🇸
Redwood City, California, United States
Integrated Research of Inland
🇺🇸
Upland, California, United States
Renstar Medical Research
🇺🇸
Ocala, Florida, United States
Asthma, Nasal Disease, and Allergy Research Center of New England
🇺🇸
East Providence, Rhode Island, United States
University of British Columbia
🇨🇦
Vancouver, British Columbia, Canada
Private Practice - Dr. Jason Ohayon
🇨🇦
Hamilton, Ontario, Canada
Timber Lane Allergy and Asthma Research, LLC
🇺🇸
Burlington, Vermont, United States
Center for Clinical Studies
🇺🇸
Cypress, Texas, United States
Lynde Institute for Dermatology
🇨🇦
Markham, Ontario, Canada
Cheema Research
🇨🇦
Mississauga, Ontario, Canada
Yang Medicine
🇨🇦
Ottawa, Ontario, Canada
Private Practice - Dr. Isabelle Delorme
🇨🇦
Drummondville, Quebec, Canada
Centre de Recherche Applique En Allergie de Quebec
🇨🇦
Quebec City, Quebec, Canada
Hautarztpraxis Mahlow
🇩🇪
Mahlow, Germany
Charite Mitte; Klinik fur Dermatologie
🇩🇪
Berlin, Germany
Licca Clinical Research Institute
🇩🇪
Augsburg, Germany
Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Augenheilkunde
🇩🇪
Dresden, Germany
Klinik für Haut- und Geschlechtskrankheiten, Universitätsklinikum Münster
🇩🇪
Münster, Germany
Vital Prospects Clinical Research Institute PC - CRN
🇺🇸
Tulsa, Oklahoma, United States
Southern California Research Center
🇺🇸
Mission Viejo, California, United States