Study to Evaluate the Safety and Antiviral Activity of Inarigivir Soproxil (Formerly: GS-9992) Plus Tenofovir Alafenamide (TAF) for 12 Weeks in Adults With Chronic Hepatitis B (CHB)

Study Overview
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Brief Summary
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The primary objectives of this study are to evaluate the safety and tolerability of the 12 week treatment regimens of inarigivir soproxil plus tenofovir alafenamide (TAF) or commercially available nucleoside/nucleotide (NUC) in adults with chronic hepatitis B (CHB), to evaluate the antiviral activity of 12 weeks of inarigivir soproxil plus TAF versus TAF alone in viremic CHB participants (Groups 1-3, 5), and to evaluate the antiviral activity of 12 weeks of inarigivir soproxil with commercially available NUC(s) in virally suppressed CHB participants (Group 4).

Official Title
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A Phase 2, Randomized, Open-Label, Active-Controlled Study to Evaluate the Safety and Antiviral Activity of GS-9992 Plus Tenofovir Alafenamide (TAF) for 12 Weeks in Chronic Hepatitis B (CHB) Subjects

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: Inarigivir Soproxil
* Drug: TAF


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Groups 1-3 and 5: Individuals not taking any prescribed hepatitis B virus (HBV) NUC treatment Group 4: HBV deoxyribonucleic acid (DNA) ≤ 20 IU/mL at Screening by Central Lab. Have been on a commercially available HBV NUC treatment(s) Key Exclusion Criteria: Co-infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or hepatitis D virus (HDV). Extensive bridging fibrosis or cirrhosis Evidence of hepatocellular carcinoma on imaging Any history of, or current evidence of, clinical hepatic decompensation (e.g., ascites, encephalopathy or variceal hemorrhage). Chronic liver disease of a non-HBV etiology Current alcohol or substance abuse Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Group 1: Inarigivir Soproxil 50 mg + TAF<br>Viremic participants will be administered inarigivir soproxil 50 mg (2 x 25 mg capsules) once daily orally 1 hour before or 1 hour after a meal plus TAF 25 mg tablet once daily orally with food for 12 weeks followed by TAF 25 mg tablet once daily orally with food for 36 weeks. | Drug: Inarigivir Soproxil<br>* Administered orally once daily one hour before or one hour after a meal<br>* Other names: GS-9992;Drug: TAF<br>* Administered orally once daily with food<br>* Other names: Vemlidy®;|
| Experimental: Group 2: TAF<br>Viremic participants will be administered TAF 25 mg tablet once daily orally with food for 48 weeks. | Drug: TAF<br>* Administered orally once daily with food<br>* Other names: Vemlidy®;|
| Experimental: Group 3: Inarigivir Soproxil 200 mg + TAF<br>Viremic participants will be administered inarigivir soproxil 200 mg (2 x 100 mg tablets) once daily orally 1 hour before or 1 hour after a meal plus TAF 25 mg tablet once daily orally with food for 12 weeks followed by TAF 25 mg tablet once daily orally with food for 36 weeks | Drug: Inarigivir Soproxil<br>* Administered orally once daily one hour before or one hour after a meal<br>* Other names: GS-9992;Drug: TAF<br>* Administered orally once daily with food<br>* Other names: Vemlidy®;|
| Experimental: Group 4: Inarigivir Soproxil 100 mg + commercially available NUCs<br>Virally suppressed participants receiving commercially available nucleoside/nucleotide (NUC) will be administered inarigivir soproxil 100 mg tablet once daily orally 1 hour before or 1 hour after a meal for 12 weeks. Participants will continue commercially available NUCs for 48 weeks. | Drug: Inarigivir Soproxil<br>* Administered orally once daily one hour before or one hour after a meal<br>* Other names: GS-9992;|
| Experimental: Group 5: Inarigivir Soproxil 400 mg + TAF<br>Viremic participants will be administered inarigivir soproxil 400 mg (2 x 200 mg tablets) once daily orally 1 hour before or 1 hour after a meal plus TAF 25 mg tablet once daily orally with food for 12 weeks followed TAF 25 mg tablet once daily orally with food for 36 weeks. | Drug: Inarigivir Soproxil<br>* Administered orally once daily one hour before or one hour after a meal<br>* Other names: GS-9992;Drug: TAF<br>* Administered orally once daily with food<br>* Other names: Vemlidy®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With ≥ 0.5 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Groups 1-3 and 5) |  | Baseline, Week 12 | 
| Percentage of Participants With ≥ 0.5 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Group 4) |  | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With ≥ 1 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Groups 1 Through 3 and 5) |  | Baseline, Week 12 | 
| Percentage of Participants With ≥ 1 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Group 4) |  | Baseline, Week 12 | 
| Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | HBeAg loss was defined as qualitative HBeAg result changing from positive at baseline to negative at post-baseline visit. HBeAg seroconversion was defined as HBeAb changing from negative or missing at baseline to positive at any postbaseline visit. Participants who had missing information were assumed to have no HBeAg loss and no HBeAg seroconversion. | Baseline, Weeks 12, 24, 36, and 48 | 
| Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Group 4) | HBeAg loss was defined as qualitative HBeAg result changing from positive at baseline to negative at post-baseline visit. HBeAg seroconversion was defined as HBeAb changing from negative or missing at baseline to positive at any postbaseline visit. Participants who had missing information were assumed to have no HBeAg loss and no HBeAg seroconversion. | Baseline, Weeks 12, 24, 36, and 48 | 
| Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | HBeAg loss was defined as qualitative HBeAg result changing from positive at baseline to negative at post-baseline visit. Participants who had missing information were assumed to have no HBeAg loss. | Baseline, Weeks 12, 24, 36, and 48 | 
| Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Group 4) | HBeAg loss was defined as qualitative HBeAg result changing from positive at baseline to negative at post-baseline visit. | Baseline, Weeks 12, 24, 36, and 48 | 
| Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase for Participants Who Had HBV DNA ≥ 69 IU/mL (Groups 1 Through 3 and 5) |  | Baseline, Week 48 | 
| Percentage of Participants Experiencing Hepatitis B Virus (HBV) Virologic Breakthrough During 12 Weeks of Inarigivir Soproxil Treatment (Group 4) | Virologic breakthrough was defined as HBV deoxyribonucleic acid (DNA) ≥69 IU/mL for 2 consecutive visits | Baseline up to Week 12 | 
| Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) |  | Baseline, Weeks 12, 16, 24, 36, and 48 | 
| Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) |  | Baseline, Weeks 12, 16, 24, 36, and 48 | 
| Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Group 4) |  | Baseline, Weeks 12, 16, 24, 36, and 48 |