Study to Evaluate the Safety, Tolerability, and Efficacy of Vesatolimod in Combination With Tenofovir Disoproxil Fumarate (TDF) in Adults With Chronic Hepatitis B (CHB) Infection Who Are Currently Not Being Treated

Gilead Sciences192 enrolled

Overview

The primary objectives of this study are to evaluate the safety, tolerability, and efficacy of vesatolimod (formerly GS-9620) in adults with chronic hepatitis B (CHB) infection who are currently not being treated.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

192

Conditions

Chronic Hepatitis B

Interventions

TDFDRUG

300 mg tablets administered orally once daily

VesatolimodDRUG

Tablets administered orally once a week (every 7 days) for 12 doses

PlaceboDRUG

Placebo administered orally once a week (every 7 days) for 12 doses

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Adult males or females between the ages of 18-65 * Chronic hepatitis B virus (HBV) infection * HBV deoxyribonucleic acid (DNA ) ≥ 2000 IU/mL at screening Key Exclusion Criteria: * Extensive bridging fibrosis or cirrhosis * Received oral antiviral treatment for HBV or prolonged therapy with immune-modulators or biologics within 3 months of screening * Co-infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV) or hepatitis D virus (HDV) * Chronic liver disease other than HBV * Lactating or pregnant females or those that wish to become pregnant during the course of the study Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Locations (21)

Unnamed facility

Los Angeles, California, United States

Unnamed facility

Palo Alto, California, United States

Unnamed facility

San Diego, California, United States

Outcomes

Primary Outcomes

Mean Change (Measured in log10 IU/mL) in Hepatitis B Surface Antigen (HBsAg) From Baseline at Week 24

The change from baseline to Week 24 in HBsAg (log10 IU/mL) was analyzed using a mixed model for repeated measures (MMRM). The model included treatment, baseline HBsAg (log10 IU/mL), baseline Hepatitis B Envelope Antigen (HBeAg) status (positive or negative), baseline alanine aminotransferase (ALT) level relative to upper limit of normal (ULN) (\> 19 vs ≤ 19 IU/L for females; \> 30 vs ≤ 30 IU/L for males), visit and treatment-by-visit interaction as fixed effects, and visit as a repeated measure.

Time frame: Baseline; Week 24

Secondary Outcomes

Percentage of Participants With HBeAg Loss and Seroconversion at Week 24

HBeAg loss was defined as qualitative HBeAg result changing from positive at baseline to negative at any postbaseline visit. HBeAg seroconversion was defined as qualitative Hepatitis B Envelope Antibody (HBeAb) result changing from negative at baseline to positive at any postbaseline visit. The Missing (M) = Failure (F) approach was used for this analysis.

Time frame: Week 24

Percentage of Participants With HBeAg Loss and Seroconversion at Week 48

HBeAg loss was defined as qualitative HBeAg result changing from positive at baseline to negative at any postbaseline visit. HBeAg seroconversion was defined as qualitative HBeAb result changing from negative at baseline to positive at any postbaseline visit. The Missing (M) = Failure (F) approach was used for this analysis.

Time frame: Week 48

Percentage of Participants With HBsAg Loss and Seroconversion at Week 24

HBsAg loss was defined as qualitative HBsAg result changing from positive at baseline to negative at any postbaseline visit. HBsAg seroconversion was defined as qualitative Hepatitis B Surface Antibody (HBsAb) result changing from negative at baseline to positive at any postbaseline visit. The Missing (M) = Failure (F) approach was used for this analysis.

Data from ClinicalTrials.gov

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Unnamed facility

San Francisco, California, United States

Unnamed facility

Honolulu, Hawaii, United States

Unnamed facility

Catonsville, Maryland, United States

Unnamed facility

Boston, Massachusetts, United States

Unnamed facility

Flushing, New York, United States

Unnamed facility

Philadelphia, Pennsylvania, United States

Unnamed facility

Toronto, Ontario, Canada

...and 11 more locations

Percentage of Participants With HBsAg Loss and Seroconversion at Week 48

HBsAg loss was defined as qualitative HBsAg result changing from positive at baseline to negative at any postbaseline visit. HBsAg seroconversion was defined as qualitative HBsAb result changing from negative at baseline to positive at any postbaseline visit. The Missing (M) = Failure (F) approach was used for this analysis.

Time frame: Week 48

Mean Change (Measured in log10 IU/mL) in HBsAg From Baseline at Week 12

Time frame: Baseline; Week 12

Mean Change (Measured in log10 IU/mL) in HBsAg From Baseline at Week 48

Time frame: Baseline; Week 48

Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 12

HBsAg ≥ 0.5 log10 IU/mL decline was defined as a decline from baseline in log10 IU/mL serum HBsAg ≥ 0.5 at the Week 12 post-baseline visit. Missing values were considered failures.

Time frame: Baseline to Week 12

Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 24

HBsAg ≥ 0.5 log10 IU/mL decline was defined as a decline from baseline in log10 IU/mL serum HBsAg ≥ 0.5 at the Week 24 post-baseline visit.

Time frame: Baseline to Week 24

Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 48

HBsAg ≥ 0.5 log10 IU/mL decline was defined as a decline from baseline in log10 IU/mL serum HBsAg ≥ 0.5 at the Week 12 post-baseline visit. Missing values were considered failures.

Time frame: Baseline to Week 48

Percentage of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantitation (LLOQ) at Week 24

LLOQ for HBV DNA was defined as 20 IU/mL. The participants with missing information were excluded from the analysis.

Time frame: Week 24

Percentage of Participants With HBV DNA < LLOQ at Week 48

LLOQ for HBV DNA was defined as 20 IU/mL. The participants with missing information were excluded from the analysis.

Time frame: Week 48

Percentage of Participants Experiencing Virologic Breakthrough

Virologic breakthrough was defined as confirmed HBV DNA ≥ 69 IU/mL after having had HBV DNA \< 69 IU/mL or confirmed 1.0 log10 IU/mL or greater increase in HBV DNA from nadir. Confirmation requires 2 consecutive occurrences of elevation in HBV DNA to \> 69 IU/mL after having had HBV DNA \< 69 IU/mL or 1.0 log10 IU/mL or greater increases in HBV DNA from nadir.

Time frame: Weeks 24 and 48

Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase/Reverse Transcriptase (Pol/RT)

Sequence analysis of the HBV pol/RT was attempted for any participant who had HBV DNA ≥ 69 IU/mL at Week 48 or early discontinuation. Results of the alignment of Week 48 and baseline sequence were reported as a change from baseline sequence.

Time frame: Baseline; Week 48

Pharmacokinetic (PK) Parameter: AUClast of Vesatolimod

AUClast is defined as the area under the concentration versus time curve from time zero to the last quantifiable concentration.