Clinical trial NCT02174276: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis B
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2014-06-25
Enrollment: 195
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Key Inclusion Criteria:

* 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)

Key Exclusion Criteria:

* 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
* Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc). Individuals under evaluation for possible malignancy are not eligible

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Mean Change in Serum HBsAg From Baseline to Week 24
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Mean Change in HBsAg From Baseline to Week 12
timeFrame: Baseline to Week 12
measure: Mean Change in HBsAg From Baseline to Week 48
timeFrame: Baseline to Week 48
measure: Percentage of Participants With HBsAg Loss at Week 24
timeFrame: Baseline to Week 24
measure: Percentage of Participants With HBsAg Loss at Week 48
timeFrame: Baseline to Week 48
measure: Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 24
timeFrame: Baseline to Week 24
measure: Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 48
timeFrame: Baseline to Week 48
measure: Percentage of Participants With a ≥ 0.5 Log10 IU/mL or a ≥ 1.0 Log10 IU/mL Decline in HBsAg at Week 12
timeFrame: Baseline to Week 12
measure: Percentage of Participants With a ≥ 0.5 Log10 IU/mL or a ≥ 1.0 Log10 IU/mL Decline in HBsAg at Week 24
timeFrame: Baseline to Week 24
measure: Percentage of Participants With a ≥ 0.5 Log10 IU/mL or a ≥ 1.0 Log10 IU/mL Decline in HBsAg at Week 48
timeFrame: Baseline to Week 48
measure: Percentage of Participants With HBeAg Loss at Week 24
timeFrame: Baseline to Week 24
measure: Percentage of Participants With HBeAg Loss at Week 48
timeFrame: Baseline to Week 48
measure: Composite Endpoint Measuring the Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 24
timeFrame: Baseline to Week 24
measure: Composite Endpoint Measuring the Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 48
timeFrame: Baseline to Week 48
measure: Percentage of Participants With HBV DNA < Lower Limit of Quantification (LLOQ) at Week 24
timeFrame: Week 24
measure: Percentage of Participants With HBV DNA < LLOQ at Week 48
timeFrame: Week 48
measure: Percentage of Participants Experiencing Virologic Breakthrough at Week 24
timeFrame: Baseline to Week 24
measure: Percentage of Participants Experiencing Virologic Breakthrough at Week 48
timeFrame: Baseline to Week 48
measure: Number of Participants With Drug-Resistance Mutations at Week 48 or at the Last Visit Available
timeFrame: Baseline to Week 48
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente
state: California
city: San Diego
country: United States
facility: Research and Education, Inc.
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente San Francisco
state: California
city: San Jose
country: United States
facility: Silicon Valley Research Institute
state: California
city: Honolulu
country: United States
facility: The Queen's Medical Center
state: Hawaii
city: Baltimore
country: United States
facility: Digestive Disease Associates, PA
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Philadelphia
country: United States
facility: Xiaoli Ma, PC
state: Pennsylvania
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Springfield
country: United States
facility: Kaiser Permanente
state: Virginia
city: Vancouver
country: Canada
facility: Gordon & Leslie Diamond Health Care Centre
state: British Columbia
city: Vancouver
country: Canada
facility: Liver and Intestinal Research Center
state: British Columbia
city: Winnipeg
country: Canada
facility: University of Manitoba
state: Manitoba
city: Toronto
country: Canada
facility: Toronto General Hospital-The University Health Network
state: Ontario
city: Toronto
country: Canada
facility: Toronto Liver Centre
state: Ontario
city: Toronto
country: Canada
facility: Toronto Western Hospital-The University Health Network
state: Ontario
city: Bologna
country: Italy
facility: Aou-S.Orsola-Malpighi - Universita Degli Studi Di
city: Parma
country: Italy
facility: Azienda Ospedaliero-Universitaria di Parma
city: Pisa
country: Italy
facility: Azienda Ospedaliero-Universitaria Pisana
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Casa Sollievo della Sofferenza
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Seocho
country: Korea, Republic of
facility: The Catholic University of Korea
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University College of Medicine
city: Seoul
country: Korea, Republic of
facility: Yonsei Universiity
city: Yangsan
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
city: Yangsan
country: Korea, Republic of
facility: The Catholic University of Korea
city: Auckland
country: New Zealand
facility: Auckland Clinical Studies
city: Bucharest
country: Romania
facility: Dr. Victor Babes Hospital for Infectious Diseases
city: Bucharest
country: Romania
facility: Institutul National de Boli Infectioase Prof.Dr. Matei Bals
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Boni 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.