Clinical trial NCT03137069: A Study of GDC-0853 in Participants With Refractory Chronic Spontaneous Urticaria (CSU).
Official title: A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled Pilot and Dose-Ranging Study of GDC-0853 in Patients With Refractory Chronic Spontaneous Urticaria (CSU).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Urticaria
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2017-05-02
Enrollment: 134
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change From Baseline in the Urticaria Activity Score Over 7 Days (UAS7) at Day 57
timeFrame: Baseline and Day 57
Secondary outcomes:
measure: Percentage of Participants Who Are Well-Controlled (UAS7 ≤ 6)
timeFrame: Day 57
measure: Change From Baseline in the UAS7 at Day 29
timeFrame: Baseline and Day 29
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Baseline up until 4 weeks after the last dose of study drug (up to 2 years, 5 months).
measure: Plasma Concentrations of Fenebrutinib (GDC-0853) at Specified Timepoints
timeFrame: Days 1, 8 and 57.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Clinical Research Center of Alabama, LLC
state: Alabama
city: Scottsdale
country: United States
facility: Allergy & Asthma Immunology Associates
state: Arizona
city: Bakersfield
country: United States
facility: Kern Allergy Med Clinic, Inc.
state: California
city: Mission Viejo
country: United States
facility: Southern California Research Center
state: California
city: Redwood City
country: United States
facility: Allergy & Asthma Consultants
state: California
city: Riverside
country: United States
facility: Integrated Research Group Inc
state: California
city: Upland
country: United States
facility: Integrated Research of Inland
state: California
city: Miami
country: United States
facility: New Horizon Research Center
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Tulsa
country: United States
facility: Vital Prospects Clinical Research Institute PC - CRN
state: Oklahoma
city: East Providence
country: United States
facility: Asthma, Nasal Disease, and Allergy Research Center of New England
state: Rhode Island
city: Cypress
country: United States
facility: Center for Clinical Studies
state: Texas
city: Burlington
country: United States
facility: Timber Lane Allergy and Asthma Research, LLC
state: Vermont
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: Hamilton
country: Canada
facility: Private Practice - Dr. Jason Ohayon
state: Ontario
city: Markham
country: Canada
facility: Lynde Institute for Dermatology
state: Ontario
city: Mississauga
country: Canada
facility: Cheema Research
state: Ontario
city: Ottawa
country: Canada
facility: Yang Medicine
state: Ontario
city: Toronto
country: Canada
facility: Gordon Sussman Clinical Research
state: Ontario
city: Drummondville
country: Canada
facility: Private Practice - Dr. Isabelle Delorme
state: Quebec
city: Quebec City
country: Canada
facility: Centre de Recherche Applique En Allergie de Quebec
state: Quebec
city: Augsburg
country: Germany
facility: Licca Clinical Research Institute
city: Berlin
country: Germany
facility: Charite Mitte; Klinik fur Dermatologie
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Augenheilkunde
city: Mahlow
country: Germany
facility: Hautarztpraxis Mahlow
city: Mainz
country: Germany
facility: Universitätsmedizin Johannes Gutenberg Universität
city: Münster
country: Germany
facility: Klinik für Haut- und Geschlechtskrankheiten, Universitätsklinikum Münster
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: