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

Urticaria Clinical Trial

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).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03137069
• Other study ID #: GS39684
• Secondary ID: 2016-004624-35
• Status: Completed
• Phase: Phase 2
• Start date: May 26, 2017
• Est. completion date: October 25, 2019

Study information

• Verified date: September 2020
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 134
• Est. completion date: October 25, 2019
• Est. primary completion date: September 27, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Urticaria

Intervention

Drug:
• GDC-0853
GDC-0853 will be administered orally at dosages of 50, 150 and 200mg to participants, as per the dosing schedules described above.
• Placebo
Matching Placebo will be administered orally, as per the dosing schedules described above.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in the Urticaria Activity Score Over 7 Days (UAS7) at 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.	Baseline and Day 57
Secondary	Percentage of Participants Who Are Well-Controlled (UAS7 = 6)	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.	Day 57
Secondary	Change From Baseline in the UAS7 at 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.	Baseline and Day 29
Secondary	Percentage of Participants With Adverse Events (AEs)	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.	Baseline up until 4 weeks after the last dose of study drug (up to 2 years, 5 months).
Secondary	Plasma Concentrations of Fenebrutinib (GDC-0853) at Specified Timepoints	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.	Days 1, 8 and 57.