Safety and Efficacy of GS-4774 in Combination With Tenofovir Disoproxil Fumarate (TDF) for the Treatment of Participants With Chronic Hepatitis B (CHB) and Who Are Currently Not on Treatment
A Phase 2, Randomized, Open-Label Study to Evaluate the Safety and Efficacy of GS-4774 in Combination With Tenofovir Disoproxil Fumarate (TDF) for the Treatment of Subjects With Chronic Hepatitis B and Who Are Currently Not on Treatment
2 other identifiers
interventional
195
6 countries
33
Brief Summary
The primary objectives of this study are to evaluate the safety, tolerability, and efficacy of GS-4774 in adults with CHB and who are currently not on treatment. Participants will be randomized to receive TDF alone or GS-4774 plus TDF for 20 weeks. After Week 20, GS-4774 will be discontinued. All participants will continue on TDF and will be followed for an additional 28 weeks. Following completion of the 48 week study period, all participants will be eligible for a treatment extension for 96 weeks.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jul 2014
Typical duration for phase_2
33 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 23, 2014
CompletedFirst Posted
Study publicly available on registry
June 25, 2014
CompletedStudy Start
First participant enrolled
July 24, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 17, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
May 30, 2018
CompletedResults Posted
Study results publicly available
June 4, 2019
CompletedJune 4, 2019
May 1, 2019
1.6 years
June 23, 2014
May 15, 2019
May 15, 2019
Conditions
Outcome Measures
Primary Outcomes (1)
Mean Change in Serum HBsAg From Baseline to Week 24
The change from baseline to Week 24 in HBsAg was analyzed using a mixed effect model for repeated measures (MMRM). The model included treatment groups, ALT levels (\> ULN or ≤ ULN) at baseline, HBeAg status (positive or negative) at baseline, HBsAg level at baseline, visit and treatment-by-visit interaction as fixed effects and visit as a repeated measurement. Estimated least square means of treatment effects are presented with the 95% confidence intervals (CIs).
Baseline to Week 24
Secondary Outcomes (18)
Mean Change in HBsAg From Baseline to Week 12
Baseline to Week 12
Mean Change in HBsAg From Baseline to Week 48
Baseline to Week 48
Percentage of Participants With HBsAg Loss at Week 24
Baseline to Week 24
Percentage of Participants With HBsAg Loss at Week 48
Baseline to Week 48
Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 24
Baseline to Week 24
- +13 more secondary outcomes
Study Arms (4)
TDF 48 weeks
ACTIVE COMPARATORParticipants will receive TDF for 48 weeks. After Week 48, participants will have the option to continue receiving TDF for up to 144 weeks.
TDF plus GS-4774 2 YU
EXPERIMENTALParticipants will receive TDF plus GS-4774 2 yeast units (YU) for 20 weeks. After Week 20, GS-4774 will be discontinued and participants will continue on TDF for an additional 28 weeks. After Week 48, participants will have the option to continue receiving TDF for up to 144 weeks.
TDF plus GS-4774 10 YU
EXPERIMENTALParticipants will receive TDF plus GS-4774 10 YU for 20 weeks. After Week 20, GS-4774 will be discontinued and participants will continue on TDF for an additional 28 weeks. After Week 48, participants will have the option to continue receiving TDF for up to 144 weeks.
TDF plus GS-4774 40 YU
EXPERIMENTALParticipants will receive TDF plus GS-4774 40 YU for 20 weeks. After Week 20, GS-4774 will be discontinued and participants will continue on TDF for an additional 28 weeks. After Week 48, participants will have the option to continue receiving TDF for up to 144 weeks.
Interventions
TDF 300 mg tablet administered orally once daily
GS-4774 subcutaneous injection administered every 4 weeks for a total of 6 doses
Eligibility Criteria
You may qualify if:
- Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study
- Documented evidence of chronic hepatitis B virus (HBV) infection, for example, hepatitis B surface antigen (HBsAg) positive for more than 6 months
- Screening HBV DNA ≥ 2000 IU/mL
- A negative serum pregnancy test is required for females (unless surgically sterile or \> 2 years post-menopausal)
You may not qualify if:
- Cirrhosis
- Inadequate liver function
- Co-infection with hepatitis C virus (HCV), HIV or hepatitis D virus (HDV)
- Received antiviral treatment for HBV within 3 months of screening
- Evidence of hepatocellular carcinoma (eg, as evidenced by recent imaging)
- Significant cardiovascular, pulmonary, or neurological disease
- Women who are pregnant or may wish to become pregnant during the course of the study
- Received solid organ or bone marrow transplant
- Received prolonged therapy with immunomodulators (eg, corticosteroids) or biologics (eg, monoclonal antibody, interferon) within 3 months of screening
- Use of investigational agents within 3 months of screening
- Current alcohol or substance abuse judged by the investigator to potentially interfere with individual's compliance
- Receipt of immunoglobulin or other blood products within 3 months prior to enrollment
- History of demyelinating disease (Guillain-Barre), Bell's Palsy, Crohn's disease, Ulcerative colitis, or autoimmune disease
- Documented history of yeast allergy
- Known hypersensitivity to study drugs, metabolites or formulation excipients
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Gilead Scienceslead
Study Sites (33)
Stanford University Medical Center
Palo Alto, California, United States
Kaiser Permanente
Sacramento, California, United States
Research and Education, Inc.
San Diego, California, United States
Kaiser Permanente San Francisco
San Francisco, California, United States
Silicon Valley Research Institute
San Jose, California, United States
The Queen's Medical Center
Honolulu, Hawaii, United States
Digestive Disease Associates, PA
Baltimore, Maryland, United States
Tufts Medical Center
Boston, Massachusetts, United States
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Xiaoli Ma, PC
Philadelphia, Pennsylvania, United States
Virginia Commonwealth University
Richmond, Virginia, United States
Kaiser Permanente
Springfield, Virginia, United States
Gordon & Leslie Diamond Health Care Centre
Vancouver, British Columbia, Canada
Liver and Intestinal Research Center
Vancouver, British Columbia, Canada
University of Manitoba
Winnipeg, Manitoba, Canada
Toronto General Hospital-The University Health Network
Toronto, Ontario, Canada
Toronto Liver Centre
Toronto, Ontario, Canada
Toronto Western Hospital-The University Health Network
Toronto, Ontario, Canada
Aou-S.Orsola-Malpighi - Universita Degli Studi Di
Bologna, Italy
Azienda Ospedaliero-Universitaria di Parma
Parma, Italy
Azienda Ospedaliero-Universitaria Pisana
Pisa, Italy
IRCCS Casa Sollievo della Sofferenza
San Giovanni Rotondo, Italy
Auckland Clinical Studies
Auckland, New Zealand
Dr. Victor Babes Hospital for Infectious Diseases
Bucharest, Romania
Institutul National de Boli Infectioase Prof.Dr. Matei Bals
Bucharest, Romania
Kyungpook National University Hospital
Daegu, South Korea
The Catholic University of Korea
Seocho, South Korea
Seoul National University Bundang Hospital
Seongnam, South Korea
Samsung Medical Center
Seoul, South Korea
Seoul National University College of Medicine
Seoul, South Korea
Yonsei Universiity
Seoul, South Korea
Pusan National University Yangsan Hospital
Yangsan, South Korea
The Catholic University of Korea
Yangsan, South Korea
Related Publications (2)
Janssen HL, Yoon SK, Yoshida EM, Trinh HN, Rodell TC, Nguyen AH, et al. Safety and Efficacy of GS-4774 in combination with TDF in Patients with Chronic Hepatitis B not on Antiviral Medication [Abstract 231]. Hepatology AASLD Abstracts 2016;64 (Suppl S1):122A.
RESULTBoni C, Janssen HLA, Rossi M, Yoon SK, Vecchi A, Barili V, Yoshida EM, Trinh H, Rodell TC, Laccabue D, Alfieri A, Brillo F, Fisicaro P, Acerbi G, Pedrazzi G, Andreone P, Cursaro C, Margotti M, Santoro R, Piazzolla V, Brunetto MR, Coco B, Cavallone D, Zhao Y, Joshi A, Woo J, Lau AH, Gaggar A, Subramanian GM, Massetto B, Fung S, Ahn SH, Ma X, Mangia A, Ferrari C. Combined GS-4774 and Tenofovir Therapy Can Improve HBV-Specific T-Cell Responses in Patients With Chronic Hepatitis. Gastroenterology. 2019 Jul;157(1):227-241.e7. doi: 10.1053/j.gastro.2019.03.044. Epub 2019 Mar 28.
PMID: 30930022RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Gilead Clinical Study Information Center
- Organization
- Gilead Sciences
Study Officials
- STUDY DIRECTOR
Gilead Study Director
Gilead Sciences
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 23, 2014
First Posted
June 25, 2014
Study Start
July 24, 2014
Primary Completion
February 17, 2016
Study Completion
May 30, 2018
Last Updated
June 4, 2019
Results First Posted
June 4, 2019
Record last verified: 2019-05