A Study of GDC-0853 in Participants With Refractory Chronic Spontaneous Urticaria (CSU).
Primary Purpose
Urticaria
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
GDC-0853
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Urticaria
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
Sites / Locations
- Clinical Research Center of Alabama, LLC
- Allergy & Asthma Immunology Associates
- Kern Allergy Med Clinic, Inc.
- Southern California Research Center
- Allergy & Asthma Consultants
- Integrated Research Group Inc
- Integrated Research of Inland
- New Horizon Research Center
- Renstar Medical Research
- Vital Prospects Clinical Research Institute PC - CRN
- Asthma, Nasal Disease, and Allergy Research Center of New England
- Center for Clinical Studies
- Timber Lane Allergy and Asthma Research, LLC
- University of British Columbia
- Private Practice - Dr. Jason Ohayon
- Lynde Institute for Dermatology
- Cheema Research
- Yang Medicine
- Gordon Sussman Clinical Research
- Private Practice - Dr. Isabelle Delorme
- Centre de Recherche Applique En Allergie de Quebec
- Licca Clinical Research Institute
- Charite Mitte; Klinik fur Dermatologie
- Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Augenheilkunde
- Hautarztpraxis Mahlow
- Universitätsmedizin Johannes Gutenberg Universität
- Klinik für Haut- und Geschlechtskrankheiten, Universitätsklinikum Münster
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Experimental
Experimental
Arm Label
Cohort 1: Placebo
Cohort 1: GDC-0853 200mg BID
Cohort 2: Placebo
Cohort 2: GDC-0853 50mg QD
Cohort 2: GDC-0853 150mg QD
Cohort 2: GDC-0853 200mg BID
Arm Description
Participants received matching placebo twice daily from Day 1 to 56.
Participants received GDC-0853 200mg twice daily from Day 1 to 56.
Participants received matching placebo up to twice daily from Day 1 to 56.
Participants received GDC-0853 50mg once daily from Day 1 to 56.
Participants received GDC-0853 150mg once daily from Day 1 to 56.
Participants received GDC-0853 200mg twice daily from Day 1 to 56.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03137069
Brief Title
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
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
May 26, 2017 (Actual)
Primary Completion Date
September 27, 2019 (Actual)
Study Completion Date
October 25, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urticaria
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
134 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1: Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received matching placebo twice daily from Day 1 to 56.
Arm Title
Cohort 1: GDC-0853 200mg BID
Arm Type
Experimental
Arm Description
Participants received GDC-0853 200mg twice daily from Day 1 to 56.
Arm Title
Cohort 2: Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received matching placebo up to twice daily from Day 1 to 56.
Arm Title
Cohort 2: GDC-0853 50mg QD
Arm Type
Experimental
Arm Description
Participants received GDC-0853 50mg once daily from Day 1 to 56.
Arm Title
Cohort 2: GDC-0853 150mg QD
Arm Type
Experimental
Arm Description
Participants received GDC-0853 150mg once daily from Day 1 to 56.
Arm Title
Cohort 2: GDC-0853 200mg BID
Arm Type
Experimental
Arm Description
Participants received GDC-0853 200mg twice daily from Day 1 to 56.
Intervention Type
Drug
Intervention Name(s)
GDC-0853
Intervention Description
GDC-0853 will be administered orally at dosages of 50, 150 and 200mg to participants, as per the dosing schedules described above.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching Placebo will be administered orally, as per the dosing schedules described above.
Primary Outcome Measure Information:
Title
Change From Baseline in the Urticaria Activity Score Over 7 Days (UAS7) at Day 57
Description
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.
Time Frame
Baseline and Day 57
Secondary Outcome Measure Information:
Title
Percentage of Participants Who Are Well-Controlled (UAS7 ≤ 6)
Description
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.
Time Frame
Day 57
Title
Change From Baseline in the UAS7 at Day 29
Description
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.
Time Frame
Baseline and Day 29
Title
Percentage of Participants With Adverse Events (AEs)
Description
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.
Time Frame
Baseline up until 4 weeks after the last dose of study drug (up to 2 years, 5 months).
Title
Plasma Concentrations of Fenebrutinib (GDC-0853) at Specified Timepoints
Description
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.
Time Frame
Days 1, 8 and 57.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Research Center of Alabama, LLC
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35209
Country
United States
Facility Name
Allergy & Asthma Immunology Associates
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85251
Country
United States
Facility Name
Kern Allergy Med Clinic, Inc.
City
Bakersfield
State/Province
California
ZIP/Postal Code
93301
Country
United States
Facility Name
Southern California Research Center
City
Mission Viejo
State/Province
California
ZIP/Postal Code
92691
Country
United States
Facility Name
Allergy & Asthma Consultants
City
Redwood City
State/Province
California
ZIP/Postal Code
94063
Country
United States
Facility Name
Integrated Research Group Inc
City
Riverside
State/Province
California
ZIP/Postal Code
92506
Country
United States
Facility Name
Integrated Research of Inland
City
Upland
State/Province
California
ZIP/Postal Code
91786
Country
United States
Facility Name
New Horizon Research Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33165
Country
United States
Facility Name
Renstar Medical Research
City
Ocala
State/Province
Florida
ZIP/Postal Code
34470
Country
United States
Facility Name
Vital Prospects Clinical Research Institute PC - CRN
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74136
Country
United States
Facility Name
Asthma, Nasal Disease, and Allergy Research Center of New England
City
East Providence
State/Province
Rhode Island
ZIP/Postal Code
02914
Country
United States
Facility Name
Center for Clinical Studies
City
Cypress
State/Province
Texas
ZIP/Postal Code
77433
Country
United States
Facility Name
Timber Lane Allergy and Asthma Research, LLC
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05403
Country
United States
Facility Name
University of British Columbia
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6T 1Z4
Country
Canada
Facility Name
Private Practice - Dr. Jason Ohayon
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8S 1G5
Country
Canada
Facility Name
Lynde Institute for Dermatology
City
Markham
State/Province
Ontario
ZIP/Postal Code
L3P 1X2
Country
Canada
Facility Name
Cheema Research
City
Mississauga
State/Province
Ontario
ZIP/Postal Code
L5A 3V4
Country
Canada
Facility Name
Yang Medicine
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1G 6C6
Country
Canada
Facility Name
Gordon Sussman Clinical Research
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4V 1R2
Country
Canada
Facility Name
Private Practice - Dr. Isabelle Delorme
City
Drummondville
State/Province
Quebec
ZIP/Postal Code
J2B 5L4
Country
Canada
Facility Name
Centre de Recherche Applique En Allergie de Quebec
City
Quebec City
State/Province
Quebec
ZIP/Postal Code
G1V 4M6
Country
Canada
Facility Name
Licca Clinical Research Institute
City
Augsburg
ZIP/Postal Code
86179
Country
Germany
Facility Name
Charite Mitte; Klinik fur Dermatologie
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Augenheilkunde
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Hautarztpraxis Mahlow
City
Mahlow
ZIP/Postal Code
15831
Country
Germany
Facility Name
Universitätsmedizin Johannes Gutenberg Universität
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Klinik für Haut- und Geschlechtskrankheiten, Universitätsklinikum Münster
City
Münster
ZIP/Postal Code
48419
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
Learn more about this trial
A Study of GDC-0853 in Participants With Refractory Chronic Spontaneous Urticaria (CSU).
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