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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multi-center Study to Evaluate the Safety and Efficacy of GS-9620 in Combination With Tenofovir Disoproxil Fumarate (TDF) for the Treatment of Subjects With Chronic Hepatitis B and Who Are Currently Not on Treatment

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: TDF
* Drug: Vesatolimod
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: TDF + placebo<br>Main Study Phase: Tenofovir disoproxil fumarate (TDF) 300 mg tablets orally once daily for up to 48 weeks + placebo administered orally once a week (every 7 days) for 12 doses. Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144. | Drug: TDF<br>* 300 mg tablets administered orally once daily<br>* Other names: Viread®;Drug: Placebo<br>* Placebo administered orally once a week (every 7 days) for 12 doses<br>|
| Experimental: TDF + Vesatolimod 1 mg<br>Main Study Phase:TDF 300 mg tablets orally once daily for up to 48 weeks + vesatolimod 1 mg tablet orally once a week (every 7 days) for 12 doses. Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144. | Drug: TDF<br>* 300 mg tablets administered orally once daily<br>* Other names: Viread®;Drug: Vesatolimod<br>* Tablets administered orally once a week (every 7 days) for 12 doses<br>* Other names: GS-9620;|
| Experimental: TDF + Vesatolimod 2 mg<br>Main Study Phase: TDF 300 mg tablets orally once daily for up to 48 weeks + vesatolimod 2 mg tablet orally once a week (every 7 days) for 12 doses. Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144. | Drug: TDF<br>* 300 mg tablets administered orally once daily<br>* Other names: Viread®;Drug: Vesatolimod<br>* Tablets administered orally once a week (every 7 days) for 12 doses<br>* Other names: GS-9620;|
| Experimental: TDF + Vesatolimod 4 mg<br>Main Study Phase: TDF 300 mg tablets orally once daily for up to 48 weeks + vesatolimod 4 mg tablet orally once a week (every 7 days) for 12 doses. Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144. | Drug: TDF<br>* 300 mg tablets administered orally once daily<br>* Other names: Viread®;Drug: Vesatolimod<br>* Tablets administered orally once a week (every 7 days) for 12 doses<br>* Other names: GS-9620;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline; Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | Week 24 | 
| 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. | Week 48 | 
| Mean Change (Measured in log10 IU/mL) in HBsAg From Baseline at Week 12 |  | Baseline; Week 12 | 
| Mean Change (Measured in log10 IU/mL) in HBsAg From Baseline at Week 48 |  | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose | 
| PK Parameter: AUCinf of Vesatolimod | AUCinf is defined as the concentration of drug extrapolated to infinite time. | Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose | 
| PK Parameter: %AUCexp of Vesatolimod | %AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf. | Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose | 
| PK Parameter: Cmax of Vesatolimod | Cmax is defined as the maximum concentration of drug. | Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose | 
| PK Parameter: Clast of Vesatolimod | Clast is defined as the last observable concentration of drug. | Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose | 
| PK Parameter: Tmax of Vesatolimod | Tmax is defined as the time (observed time point) of Cmax | Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose | 
| PK Parameter: Tlast of Vesatolimod | Tlast is defined as the time (observed time point) of Clast. | Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose | 
| PK Parameter: T1/2 of Vesatolimod | T1/2 is defined as the estimate of the terminal elimination half-life of the drug. | Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose | 
| PK Parameter: CL/F of Vesatolimod | CL/F is defined as the apparent oral clearance following administration of the drug. | Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HBV, Hepatitis, Liver Disease