A Phase 1b Study Assessing GS-7340 in Treatment-Naive Adults With Chronic Hepatitis B

Study Overview
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Brief Summary
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This is an open-label study evaluating multiple doses of GS-7340 versus Tenofovir disoproxil fumarate (TDF).

Detailed Description
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This is a randomized, open-label, active-controlled study whose primary objective is to evaluate the safety and efficacy of several doses of GS-7340. This study will evaluate the safety, viral kinetics, and antiviral activity of 4 different doses of GS-7340 over 28 days of therapy. In addition, the study will evaluate the antiviral activity of an optimal dose of GS-7340 versus 300mg Tenofovir disoproxil fumarate (TDF) over 28 days of therapy.

Official Title
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A Phase 1b Randomized, Open Label, Active-Controlled Study to Assess the Safety, Viral Kinetics, and Anti-HBV Activity of GS-7340 in Treatment-Naive Adults With Chronic Hepatitis B (CHB) Infection

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: GS-7340
* Drug: Tenofovir disoproxil fumarate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be between 18 and 65 years of age Must have Screening plasma HBV DNA ≥ 2x10^3 IU/mL Must have chronic HBV infection for at least 6 months Must have estimated creatinine clearance (CLCr) ≥ 70 mL/min Not pregnant or nursing Women must be of non-childbearing potential OR of childbearing potential with confirmed negative pregnancy tests Consistent and correct use of recommended methods of birth control for men and women Exclusion Criteria: Pregnant or lactating subjects Receipt of anti-HBV nucleoside/nucleotide therapy. Subjects who have failed prior Interferon treatment, greater than 6 months prior to screening, are permitted to participate in the study screening Known co-infection with HIV, hepatitis C virus (HCV) or hepatitis D virus (HDV) Presence of autoimmune disorders History of liver disease other than Hepatitis B History of Gilbert's Disease Any sign of decompensated liver disease Known or suspected cirrhosis Evidence of hepatocellular carcinoma Presence or history of cardiovascular disease, cardiomyopathy, and/or cardiac conduction abnormalities Electrolyte abnormalities History of treatment that permanently alters the gastric condition Alcohol or substance abuse History of bleeding diathesis Significant bone disease

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GS-7340 8mg<br>After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days. | Drug: GS-7340<br>* Subjects are randomized to receive one of four different doses of GS-7340 over 28 days of therapy.<br>|
| Experimental: GS-7340 25mg<br>After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days. | Drug: GS-7340<br>* Subjects are randomized to receive one of four different doses of GS-7340 over 28 days of therapy.<br>|
| Experimental: GS-7340 40mg<br>After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days. | Drug: GS-7340<br>* Subjects are randomized to receive one of four different doses of GS-7340 over 28 days of therapy.<br>|
| Experimental: GS-7340 120mg<br>After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days. | Drug: GS-7340<br>* Subjects are randomized to receive one of four different doses of GS-7340 over 28 days of therapy.<br>|
| Experimental: Tenofovir disoproxil fumarate 300mg<br>After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days. | Drug: Tenofovir disoproxil fumarate<br>* Subjects will receive 300mg of Tenofovir disoproxil fumarate (TDF) over 28 days of therapy<br>* Other names: Viread;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum hepatitis B virus (HBV) DNA | Time-weighted average change from baseline through Week 4 (DAVG4) in serum HBV DNA (log10 IU/mL) for GS-7340 8-, 25-, 40 and 120-mg. | Up to Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HBV DNA for tenofovir disoproxil fumarate (TDF) | Comparing the short-term antiviral activity of GS-7340 with TDF 300mg. This is measured by time-weighted average change from baseline through Week 4 (DAVG4) in serum HBV DNA (log10 IU/mL) for TDF. | Up to Week 4 | 
| Change in HBV DNA of GS-7340 through 28 days of therapy | Time weighted change from baseline to day 29 (DAVG4) in serum HBV DNA (log10 IU/mL) | Up to week 4 | 
| Pharmacokinetics (PK) of GS-7340 and/or tenofovir (TVF) following single and multiple doses of GS-7340 and TDF | GS-7340 and tenofovir (TFV) PK parameters in plasma will be calculated as applicable: Cmax, Tmax, Clast, Tlast, T1/2, λz, AUC0-t, AUC0-last, AUC0-∞, %AUCexp. PK samples are collected on: Baseline/Day 1: 0 (predose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose Additional predose plasma samples will be collected on Days 2, 5, 8, 10, 15, 19, 22, and 29/End of Treatment. | Up to week 4 | 
| Safety and Tolerability of Therapy | Safety and tolerability is measured by the incidence of adverse events and graded laboratory abnormalities | Up to week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis B, HBV, GS-7340, TDF, Tenofovir disoproxil fumarate, Gilead, Viread