A Study to Evaluate the Long-term Safety and Efficacy of Fenebrutinib in Participants Previously Enrolled in a Fenebrutinib Chronic Spontaneous Urticaria (CSU) Study

• Sponsor: Genentech, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03693625
• Collaborator: (none)
• Enrollment: 31
• Locations: 10
• Arms: 2
• Actual Duration (Months): 12.8
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a Phase II, multicenter, open-label extension (OLE) study to evaluate the long-term safety and efficacy of fenebrutinib in participants with Chronic Spontaneous Urticaria (CSU) who have completed the treatment period in a fenebrutinib CSU parent study. Participants may enroll in this OLE study at any time after completing the treatment period of the parent study. Participants will receive open-label fenebrutinib at a dose of 200 milligram (mg) orally twice a day. Treatment may continue until the end of the study.

Condition or Disease	Intervention/Treatment	Phase
Urticaria	Drug: GDC-0853	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Open-Label Extension Study To Evaluate The Long-Term Safety And Efficacy Of Fenebrutinib In Patients Previously Enrolled In A Fenebrutinib Chronic Spontaneous Urticaria Study
• Actual Study Start Date: Sep 27, 2018
• Actual Primary Completion Date: Oct 23, 2019
• Actual Study Completion Date: Oct 23, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Parent Study: GDC-0853 Participants (who had received 50, 150 and 200mg GDC-0853 in Cohort 2 of the Parent GS39684 Study) received open-label fenebrutinib/GDC-0853 at a dose of 200mg orally twice a day.	Drug: GDC-0853; Participants were administered GDC-0853 200mg orally, as per the dosing schedules described above.; Other Names: fenebrutinib, RO7010939
Placebo Comparator: Parent Study: Placebo Participants (who had received Placebo in Cohort 2 of the Parent GS39684 Study) received open-label fenebrutinib/GDC-0853 at a dose of 200mg orally twice a day.	Drug: GDC-0853; Participants were administered GDC-0853 200mg orally, as per the dosing schedules described above.; Other Names: fenebrutinib, RO7010939

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Adverse Events (AEs) [Baseline up until 4 weeks after the last dose of study drug (up to 10 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.

Secondary Outcome Measures

1. Plasma Concentrations of Fenebrutinib (GDC-0853) at Specified Timepoints [Week 1 Day 1; Weeks 12 and 24; Study Completion/Early Discontinuation]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Ability to comply with the study protocol, in the investigator's judgment

• Completion of the treatment period as specified in the parent study

• Acceptable demonstration of tolerance to study drug during the parent study as determined by the investigator or Medical Monitor

• For participants receiving treatment with proton-pump inhibitors (PPIs) or H2-receptor antagonists (H2RAs), agreement to maintain treatment at a stable dose for the first 12 weeks of the study

• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating eggs

• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm

Exclusion Criteria

• Pregnant or breastfeeding, or intending to become pregnant during the study or within 4 weeks after the final dose of fenebrutinib

• Treatment with any investigational agent or live/attenuated vaccine in the preceding 6 weeks

• Any signs or symptoms of infection judged by the investigator to be clinically significant since completing the treatment period of the parent study

• Any significant changes (e.g., events, changes in medication) occurring after completion of participation in the parent study that, in the investigator's judgment, would increase the risk of adverse events in this OLE study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Research Center of Alabama, LLC	Birmingham	Alabama	United States	35209
2	Allergy & Asthma Immunology Associates	Scottsdale	Arizona	United States	85251
3	Kern Allergy Med Clinic, Inc.	Bakersfield	California	United States	93301
4	Southern California Research Center	Mission Viejo	California	United States	92691
5	Allergy & Asthma Consultants	Redwood City	California	United States	94063
6	Integrated Research Group Inc	Riverside	California	United States	92506
7	Renstar Medical Research	Ocala	Florida	United States	34470
8	Vital Prospects Clinical Research Institute PC - CRN	Tulsa	Oklahoma	United States	74136
9	Asthma, Nasal Disease, and Allergy Research Center of New England	East Providence	Rhode Island	United States	02914
10	Timber Lane Allergy and Asthma Research, LLC	Burlington	Vermont	United States	05403

Sponsors and Collaborators

• Genentech, Inc.

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 9, 2018

More Information

Publications

None provided.

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT03693625
• Other Study ID Numbers: GS40868; 2018-002296-17
• First Posted: Oct 3, 2018
• Last Update Posted: Sep 25, 2020
• Last Verified: Aug 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Urticaria; Chronic Urticaria

Study Results

Participant Flow

Recruitment Details	The study was conducted at 9 centers in 1 country.
Pre-assignment Detail	A total of 31 participants were enrolled at 9 centers.

Arm/Group Title	Parent Study: GDC-0853	Parent Study: Placebo
Arm/Group Description	Participants (who had received 50, 150 and 200mg GDC-0853 in Cohort 2 of the Parent GS39684 Study) received open-label fenebrutinib/GDC-0853 at a dose of 200mg orally twice a day.	Participants (who had received Placebo in Cohort 2 of the Parent GS39684 Study) received open-label fenebrutinib/GDC-0853 at a dose of 200mg orally twice a day.
Period Title: Overall Study
STARTED	23	8
COMPLETED	0	0
NOT COMPLETED	23	8

Baseline Characteristics

Arm/Group Title	Parent Study: GDC-0853	Parent Study: Placebo	Total
Arm/Group Description	Participants (who had received 50, 150 and 200mg GDC-0853 in Cohort 2 of the Parent GS39684 Study) received open-label fenebrutinib/GDC-0853 at a dose of 200mg orally twice a day.	Participants (who had received Placebo in Cohort 2 of the Parent GS39684 Study) received open-label fenebrutinib/GDC-0853 at a dose of 200mg orally twice a day.	Total of all reporting groups
Overall Participants	23	8	31
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	45.7 (16.5)	40.8 (11.0)	44.5 (15.3)
Sex: Female, Male (Count of Participants)
Female	19 82.6%	6 75%	25 80.6%
Male	4 17.4%	2 25%	6 19.4%
Race/Ethnicity, Customized (Number) [Number]
Hispanic or Latino	4 17.4%	4 50%	8 25.8%
Not Hispanic or Latino	19 82.6%	3 37.5%	22 71%
Unknown	0 0%	1 12.5%	1 3.2%
Race/Ethnicity, Customized (Number) [Number]
Asian	1 4.3%	1 12.5%	2 6.5%
Black or African American	2 8.7%	1 12.5%	3 9.7%
White	20 87%	6 75%	26 83.9%

Outcome Measures

1. Primary Outcome

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 10 months).

Outcome Measure Data

Analysis Population Description

The Safety-evaluable population was defined as all participants who received at least one dose of study drug.

Arm/Group Title	Parent Study: GDC-0853	Parent Study: Placebo
Arm/Group Description	Participants (who had received 50, 150 and 200mg GDC-0853 in Cohort 2 of the Parent GS39684 Study) received open-label fenebrutinib/GDC-0853 at a dose of 200mg orally twice a day.	Participants (who had received Placebo in Cohort 2 of the Parent GS39684 Study) received open-label fenebrutinib/GDC-0853 at a dose of 200mg orally twice a day.
Measure Participants	23	8
Number [Percentage of Participants]	60.9 264.8%	62.5 781.3%

2. Secondary Outcome

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.
Time Frame	Week 1 Day 1; Weeks 12 and 24; Study Completion/Early Discontinuation

Outcome Measure Data

Analysis Population Description

The PK population was defined as all participants who received at least one dose of study drug and had at least 1 evaluable PK sample.

Arm/Group Title	Parent Study: GDC-0853	Parent Study: Placebo
Arm/Group Description	Participants (who had received 50, 150 and 200mg GDC-0853 in Cohort 2 of the Parent GS39684 Study) received open-label fenebrutinib/GDC-0853 at a dose of 200mg orally twice a day.	Participants (who had received Placebo in Cohort 2 of the Parent GS39684 Study) received open-label fenebrutinib/GDC-0853 at a dose of 200mg orally twice a day.
Measure Participants	23	8
Week 1 Day 1	NA (NA)	NA (NA)
Week 12	192 (181)	190 (278)
Week 24	130 (63.8)	467 (480)
Study Completion/Early Discontinuation	NA (NA)	NA (NA)

Adverse Events

Time Frame	Baseline up until 4 weeks after the last dose of study drug (up to 10 months).
Arm/Group Title	Parent Study: GDC-0853		Parent Study: Placebo
Arm/Group Description	Participants (who had received 50, 150 and 200mg GDC-0853 in Cohort 2 of the Parent GS39684 Study) received open-label fenebrutinib/GDC-0853 at a dose of 200mg orally twice a day.		Participants (who had received Placebo in Cohort 2 of the Parent GS39684 Study) received open-label fenebrutinib/GDC-0853 at a dose of 200mg orally twice a day.
All Cause Mortality
	Parent Study: GDC-0853		Parent Study: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/8 (0%)
Serious Adverse Events
	Parent Study: GDC-0853		Parent Study: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Parent Study: GDC-0853		Parent Study: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/23 (17.4%)		5/8 (62.5%)
Blood and lymphatic system disorders
INCREASED TENDENCY TO BRUISE	0/23 (0%)	0	1/8 (12.5%)	1
Gastrointestinal disorders
DIARRHOEA	0/23 (0%)	0	1/8 (12.5%)	1
DYSPEPSIA	0/23 (0%)	0	1/8 (12.5%)	1
GASTROOESOPHAGEAL REFLUX DISEASE	0/23 (0%)	0	1/8 (12.5%)	1
Infections and infestations
ABSCESS LIMB	0/23 (0%)	0	1/8 (12.5%)	1
ORAL HERPES	0/23 (0%)	0	1/8 (12.5%)	1
SKIN INFECTION	0/23 (0%)	0	1/8 (12.5%)	1
Investigations
ALANINE AMINOTRANSFERASE INCREASED	1/23 (4.3%)	1	1/8 (12.5%)	1
ASPARTATE AMINOTRANSFERASE INCREASED	1/23 (4.3%)	1	1/8 (12.5%)	1
BLOOD CREATINE PHOSPHOKINASE INCREASED	1/23 (4.3%)	1	1/8 (12.5%)	1
Musculoskeletal and connective tissue disorders
BACK PAIN	0/23 (0%)	0	1/8 (12.5%)	1
MUSCULOSKELETAL CHEST PAIN	0/23 (0%)	0	1/8 (12.5%)	1
MYALGIA	0/23 (0%)	0	1/8 (12.5%)	1
Nervous system disorders
HEADACHE	0/23 (0%)	0	1/8 (12.5%)	2
MIGRAINE	0/23 (0%)	0	1/8 (12.5%)	2
Renal and urinary disorders
HAEMATURIA	0/23 (0%)	0	1/8 (12.5%)	1
Respiratory, thoracic and mediastinal disorders
COUGH	0/23 (0%)	0	1/8 (12.5%)	1
Skin and subcutaneous tissue disorders
PRURITUS	0/23 (0%)	0	1/8 (12.5%)	1
RASH	0/23 (0%)	0	1/8 (12.5%)	1
URTICARIA	2/23 (8.7%)	2	0/8 (0%)	0

Limitations/Caveats

Recruitment was stopped after an interim analysis of the parent GS39684 study.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.