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

NCT03137069 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: GS396842016-004624-35
• Study Type: interventional
• Target: 134
• Locations: 3 countries
• Sites: 27

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.

Conditions

Urticaria

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Percentage of Participants Who Are Well-Controlled (UAS7 ≤ 6)

  Day 57

• Change From Baseline in the UAS7 at Day 29

  Baseline and Day 29

• 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).

• Plasma Concentrations of Fenebrutinib (GDC-0853) at Specified Timepoints

  Days 1, 8 and 57.

Study Arms (6)

Cohort 1: Placebo

PLACEBO COMPARATOR

Participants received matching placebo twice daily from Day 1 to 56.

Drug: Placebo

Cohort 1: GDC-0853 200mg BID

EXPERIMENTAL

Participants received GDC-0853 200mg twice daily from Day 1 to 56.

Drug: GDC-0853

Cohort 2: Placebo

PLACEBO COMPARATOR

Participants received matching placebo up to twice daily from Day 1 to 56.

Drug: Placebo

Cohort 2: GDC-0853 50mg QD

EXPERIMENTAL

Participants received GDC-0853 50mg once daily from Day 1 to 56.

Drug: GDC-0853

Cohort 2: GDC-0853 150mg QD

EXPERIMENTAL

Participants received GDC-0853 150mg once daily from Day 1 to 56.

Drug: GDC-0853

Cohort 2: GDC-0853 200mg BID

EXPERIMENTAL

Participants received GDC-0853 200mg twice daily from Day 1 to 56.

Drug: GDC-0853

Interventions

GDC-0853 DRUG

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

Cohort 1: GDC-0853 200mg BID; Cohort 2: GDC-0853 150mg QD; Cohort 2: GDC-0853 200mg BID; Cohort 2: GDC-0853 50mg QD

Placebo DRUG

Matching Placebo will be administered orally, as per the dosing schedules described above.

Cohort 1: Placebo; Cohort 2: Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (27)

Clinical Research Center of Alabama, LLC

Birmingham, Alabama, 35209, United States

Location

Allergy & Asthma Immunology Associates

Scottsdale, Arizona, 85251, United States

Location

Kern Allergy Med Clinic, Inc.

Bakersfield, California, 93301, United States

Location

Southern California Research Center

Mission Viejo, California, 92691, United States

Location

Allergy & Asthma Consultants

Redwood City, California, 94063, United States

Location

Integrated Research Group Inc

Riverside, California, 92506, United States

Location

Integrated Research of Inland

Upland, California, 91786, United States

Location

New Horizon Research Center

Miami, Florida, 33165, United States

Location

Renstar Medical Research

Ocala, Florida, 34470, United States

Location

Vital Prospects Clinical Research Institute PC - CRN

Tulsa, Oklahoma, 74136, United States

Location

Asthma, Nasal Disease, and Allergy Research Center of New England

East Providence, Rhode Island, 02914, United States

Location

Center for Clinical Studies

Cypress, Texas, 77433, United States

Location

Timber Lane Allergy and Asthma Research, LLC

Burlington, Vermont, 05403, United States

Location

University of British Columbia

Vancouver, British Columbia, V6T 1Z4, Canada

Location

Private Practice - Dr. Jason Ohayon

Hamilton, Ontario, L8S 1G5, Canada

Location

Lynde Institute for Dermatology

Markham, Ontario, L3P 1X2, Canada

Location

Cheema Research

Mississauga, Ontario, L5A 3V4, Canada

Location

Yang Medicine

Ottawa, Ontario, K1G 6C6, Canada

Location

Gordon Sussman Clinical Research

Toronto, Ontario, M4V 1R2, Canada

Location

Private Practice - Dr. Isabelle Delorme

Drummondville, Quebec, J2B 5L4, Canada

Location

Centre de Recherche Applique En Allergie de Quebec

Québec, Quebec, G1V 4M6, Canada

Location

Licca Clinical Research Institute

Augsburg, 86179, Germany

Location

Charite Mitte; Klinik fur Dermatologie

Berlin, 10117, Germany

Location

Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Augenheilkunde

Dresden, 01307, Germany

Location

Hautarztpraxis Mahlow

Mahlow, 15831, Germany

Location

Universitätsmedizin Johannes Gutenberg Universität

Mainz, 55131, Germany

Location

Klinik für Haut- und Geschlechtskrankheiten, Universitätsklinikum Münster

Münster, 48419, Germany

Location

MeSH Terms

Conditions

Urticaria

Interventions

fenebrutinib

Condition Hierarchy (Ancestors)

Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Limitations and Caveats

Recruitment was stopped after an interim analysis of Cohort 2 based on pre-specified internal criteria.

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2017
• First Posted: May 2, 2017
• Study Start: May 26, 2017
• Primary Completion: September 27, 2019
• Study Completion: October 25, 2019
• Last Updated: September 29, 2020
• Results First Posted: September 29, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will share

Locations

DE (6); CA (8); US (13)