Chronic Hepatitis B
Conditions
Brief summary
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).
Interventions
Administered orally once daily one hour before or one hour after a meal
DRUGTAF
Administered orally once daily with food
Sponsors
F-star Therapeutics, Inc.
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Baseline, Weeks 12, 24, 36, and 48 | 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. |
| Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Group 4) | Baseline, Weeks 12, 24, 36, and 48 | 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. |
| Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Baseline, Weeks 12, 24, 36, and 48 | 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. |
| Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Group 4) | Baseline, Weeks 12, 24, 36, and 48 | HBeAg loss was defined as qualitative HBeAg result changing from positive at baseline to negative at post-baseline visit. |
| 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 Experiencing Hepatitis B Virus (HBV) Virologic Breakthrough During 12 Weeks of Inarigivir Soproxil Treatment (Group 4) | Baseline up to Week 12 | Virologic breakthrough was defined as HBV deoxyribonucleic acid (DNA) ≥69 IU/mL for 2 consecutive visits |
| 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 | — |
| 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 With ≥ 1 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Group 4) | Baseline, Week 12 | — |
Countries
Hong Kong, South Korea
Participant flow
Recruitment details
Participants were enrolled at study sites in Hong Kong and South Korea. The first participant was screened on 28 February 2018. The last study visit occurred on 26 January 2021.
Pre-assignment details
161 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Group 1: Inarigivir Soproxil 50 mg + TAF Viremic participants were 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. | 30 |
| Group 2: TAF Viremic participants were administered TAF 25 mg tablet once daily orally with food for 48 weeks. | 12 |
| Group 3: Inarigivir Soproxil 200 mg + TAF Viremic participants were 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. | 30 |
| Group 4: Inarigivir Soproxil 100 mg + Commercially Available NUC(s) Virally suppressed participants who were receiving NUC(s) were administered inarigivir soproxil 100 mg tablet once daily orally 1 hour before or 1 hour after a meal for 12 weeks. Participants continued commercially available NUC(s) for 48 weeks. | 21 |
| Group 5: Inarigivir Soproxil 400 mg + TAF Viremic participants were 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. | 30 |
| Total | 123 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 0 | 0 | 0 | 0 |
| Overall Study | Started commercial Hepatitis B virus therapy | 10 | 3 | 11 | 3 | 17 |
| Overall Study | Withdrew consent | 1 | 0 | 3 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Group 1: Inarigivir Soproxil 50 mg + TAF | Group 2: TAF | Group 3: Inarigivir Soproxil 200 mg + TAF | Group 4: Inarigivir Soproxil 100 mg + Commercially Available NUC(s) | Group 5: Inarigivir Soproxil 400 mg + TAF |
|---|---|---|---|---|---|---|
| Age, Customized <50 years | 71 Participants | 23 Participants | 5 Participants | 19 Participants | 11 Participants | 13 Participants |
| Age, Customized ≥50 years | 52 Participants | 7 Participants | 7 Participants | 11 Participants | 10 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 123 Participants | 30 Participants | 12 Participants | 30 Participants | 21 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Hepatitis B Surface Antigen (HBsAg) Category ≤ 4 log10 IU/mL | 83 Participants | 16 Participants | 4 Participants | 23 Participants | 19 Participants | 21 Participants |
| Hepatitis B Surface Antigen (HBsAg) Category > 4 log10 IU/mL | 40 Participants | 14 Participants | 8 Participants | 7 Participants | 2 Participants | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 123 Participants | 30 Participants | 12 Participants | 30 Participants | 21 Participants | 30 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Hong Kong | 76 participants | 8 participants | 5 participants | 22 participants | 11 participants | 30 participants |
| Region of Enrollment South Korea | 47 participants | 22 participants | 7 participants | 8 participants | 10 participants | 0 participants |
| Sex: Female, Male Female | 46 Participants | 12 Participants | 3 Participants | 11 Participants | 9 Participants | 11 Participants |
| Sex: Female, Male Male | 77 Participants | 18 Participants | 9 Participants | 19 Participants | 12 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 12 | 0 / 30 | 0 / 21 | 0 / 30 |
| other Total, other adverse events | 8 / 30 | 7 / 12 | 15 / 30 | 9 / 21 | 9 / 30 |
| serious Total, serious adverse events | 1 / 30 | 1 / 12 | 1 / 30 | 0 / 21 | 1 / 30 |
Outcome results
Primary
Percentage of Participants With ≥ 0.5 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Group 4)
Time frame: Baseline, Week 12
Population: The Full Analysis Set (Group 4) included all participants who were enrolled in Group 4, and who took at least 1 dose of any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: Inarigivir Soproxil 50 mg + TAF | Percentage of Participants With ≥ 0.5 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Group 4) | 0 percentage of participants |
Primary
Percentage of Participants With ≥ 0.5 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Groups 1-3 and 5)
Time frame: Baseline, Week 12
Population: The Full Analysis Set included all participants who were randomized to Groups 1 or 2, or enrolled in Group 3 and 5, and who took at least 1 dose of any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: Inarigivir Soproxil 50 mg + TAF | Percentage of Participants With ≥ 0.5 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Groups 1-3 and 5) | 23.3 percentage of participants |
| Group 2: TAF | Percentage of Participants With ≥ 0.5 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Groups 1-3 and 5) | 25.0 percentage of participants |
| Group 3: Inarigivir Soproxil 200 mg + TAF | Percentage of Participants With ≥ 0.5 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Groups 1-3 and 5) | 0 percentage of participants |
| Group 5: Inarigivir Soproxil 400 mg + TAF | Percentage of Participants With ≥ 0.5 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Groups 1-3 and 5) | 6.7 percentage of participants |
95% CI: [-30.4, 26.4]
95% CI: [-49.2, -0.2]
95% CI: [-43.7, 8.2]
Secondary
Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Group 4)
Time frame: Baseline, Weeks 12, 16, 24, 36, and 48
Population: Participants in the Full Analysis Set (Group 4) were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Inarigivir Soproxil 50 mg + TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Group 4) | Baseline | 3.211 log10 IU/mL | Standard Deviation 0.5536 |
| Group 1: Inarigivir Soproxil 50 mg + TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Group 4) | Change at Week 12 | -0.017 log10 IU/mL | Standard Deviation 0.0417 |
| Group 1: Inarigivir Soproxil 50 mg + TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Group 4) | Change at Week 16 | -0.010 log10 IU/mL | Standard Deviation 0.0645 |
| Group 1: Inarigivir Soproxil 50 mg + TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Group 4) | Change at Week 24 | -0.039 log10 IU/mL | Standard Deviation 0.0925 |
| Group 1: Inarigivir Soproxil 50 mg + TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Group 4) | Change at Week 36 | -0.037 log10 IU/mL | Standard Deviation 0.0939 |
| Group 1: Inarigivir Soproxil 50 mg + TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Group 4) | Change at Week 48 | -0.073 log10 IU/mL | Standard Deviation 0.112 |
Secondary
Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5)
Time frame: Baseline, Weeks 12, 16, 24, 36, and 48
Population: Participants in the Full Analysis Set (Groups 1-3 and 5) with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Inarigivir Soproxil 50 mg + TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 24 | -0.310 log10 IU/mL | Standard Deviation 0.4303 |
| Group 1: Inarigivir Soproxil 50 mg + TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 36 | -0.330 log10 IU/mL | Standard Deviation 0.4363 |
| Group 1: Inarigivir Soproxil 50 mg + TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 48 | -0.322 log10 IU/mL | Standard Deviation 0.4311 |
| Group 1: Inarigivir Soproxil 50 mg + TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Baseline | 3.933 log10 IU/mL | Standard Deviation 0.8058 |
| Group 1: Inarigivir Soproxil 50 mg + TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 12 | -0.244 log10 IU/mL | Standard Deviation 0.3443 |
| Group 1: Inarigivir Soproxil 50 mg + TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 16 | -0.282 log10 IU/mL | Standard Deviation 0.3954 |
| Group 2: TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 16 | -0.479 log10 IU/mL | Standard Deviation 0.5429 |
| Group 2: TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Baseline | 4.118 log10 IU/mL | Standard Deviation 0.6543 |
| Group 2: TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 24 | -0.482 log10 IU/mL | Standard Deviation 0.5119 |
| Group 2: TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 48 | -0.517 log10 IU/mL | Standard Deviation 0.5617 |
| Group 2: TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 36 | -0.524 log10 IU/mL | Standard Deviation 0.543 |
| Group 2: TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 12 | -0.435 log10 IU/mL | Standard Deviation 0.532 |
| Group 3: Inarigivir Soproxil 200 mg + TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 36 | -0.055 log10 IU/mL | Standard Deviation 0.4213 |
| Group 3: Inarigivir Soproxil 200 mg + TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 48 | -0.045 log10 IU/mL | Standard Deviation 0.4778 |
| Group 3: Inarigivir Soproxil 200 mg + TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Baseline | 3.529 log10 IU/mL | Standard Deviation 0.8835 |
| Group 3: Inarigivir Soproxil 200 mg + TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 16 | 0.014 log10 IU/mL | Standard Deviation 0.2916 |
| Group 3: Inarigivir Soproxil 200 mg + TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 12 | 0.016 log10 IU/mL | Standard Deviation 0.285 |
| Group 3: Inarigivir Soproxil 200 mg + TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 24 | -0.021 log10 IU/mL | Standard Deviation 0.3171 |
| Group 5: Inarigivir Soproxil 400 mg + TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 12 | -0.026 log10 IU/mL | Standard Deviation 0.3805 |
| Group 5: Inarigivir Soproxil 400 mg + TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 16 | -0.082 log10 IU/mL | Standard Deviation 0.4262 |
| Group 5: Inarigivir Soproxil 400 mg + TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 36 | -0.209 log10 IU/mL | Standard Deviation 0.5319 |
| Group 5: Inarigivir Soproxil 400 mg + TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Baseline | 3.418 log10 IU/mL | Standard Deviation 0.8075 |
| Group 5: Inarigivir Soproxil 400 mg + TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 24 | -0.104 log10 IU/mL | Standard Deviation 0.5 |
| Group 5: Inarigivir Soproxil 400 mg + TAF | Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 48 | -0.235 log10 IU/mL | Standard Deviation 0.5429 |
Secondary
Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5)
Time frame: Baseline, Weeks 12, 16, 24, 36, and 48
Population: Participants in the Full Analysis Set (Groups 1-3 and 5) with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Inarigivir Soproxil 50 mg + TAF | Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 24 | -5.02 log10 IU/mL | Standard Deviation 1.101 |
| Group 1: Inarigivir Soproxil 50 mg + TAF | Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 36 | -5.27 log10 IU/mL | Standard Deviation 1.194 |
| Group 1: Inarigivir Soproxil 50 mg + TAF | Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 48 | -5.36 log10 IU/mL | Standard Deviation 1.225 |
| Group 1: Inarigivir Soproxil 50 mg + TAF | Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 16 | -4.58 log10 IU/mL | Standard Deviation 1.023 |
| Group 1: Inarigivir Soproxil 50 mg + TAF | Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Baseline | 7.06 log10 IU/mL | Standard Deviation 1.53 |
| Group 1: Inarigivir Soproxil 50 mg + TAF | Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 12 | -4.18 log10 IU/mL | Standard Deviation 0.959 |
| Group 2: TAF | Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 16 | -4.65 log10 IU/mL | Standard Deviation 1.326 |
| Group 2: TAF | Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 24 | -5.25 log10 IU/mL | Standard Deviation 1.51 |
| Group 2: TAF | Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 12 | -4.24 log10 IU/mL | Standard Deviation 1.34 |
| Group 2: TAF | Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 36 | -5.53 log10 IU/mL | Standard Deviation 1.61 |
| Group 2: TAF | Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 48 | -5.25 log10 IU/mL | Standard Deviation 1.839 |
| Group 2: TAF | Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Baseline | 7.06 log10 IU/mL | Standard Deviation 1.757 |
| Group 3: Inarigivir Soproxil 200 mg + TAF | Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Baseline | 6.30 log10 IU/mL | Standard Deviation 1.365 |
| Group 3: Inarigivir Soproxil 200 mg + TAF | Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 12 | -4.02 log10 IU/mL | Standard Deviation 0.854 |
| Group 3: Inarigivir Soproxil 200 mg + TAF | Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 16 | -4.29 log10 IU/mL | Standard Deviation 0.946 |
| Group 3: Inarigivir Soproxil 200 mg + TAF | Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 24 | -4.67 log10 IU/mL | Standard Deviation 1.049 |
| Group 3: Inarigivir Soproxil 200 mg + TAF | Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 36 | -4.78 log10 IU/mL | Standard Deviation 1.207 |
| Group 3: Inarigivir Soproxil 200 mg + TAF | Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 48 | -4.83 log10 IU/mL | Standard Deviation 1.162 |
| Group 5: Inarigivir Soproxil 400 mg + TAF | Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 48 | -4.93 log10 IU/mL | Standard Deviation 1.37 |
| Group 5: Inarigivir Soproxil 400 mg + TAF | Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 36 | -4.92 log10 IU/mL | Standard Deviation 1.129 |
| Group 5: Inarigivir Soproxil 400 mg + TAF | Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 12 | -3.93 log10 IU/mL | Standard Deviation 0.817 |
| Group 5: Inarigivir Soproxil 400 mg + TAF | Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Baseline | 6.61 log10 IU/mL | Standard Deviation 1.479 |
| Group 5: Inarigivir Soproxil 400 mg + TAF | Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 24 | -4.76 log10 IU/mL | Standard Deviation 1.013 |
| Group 5: Inarigivir Soproxil 400 mg + TAF | Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) | Change at Week 16 | -4.23 log10 IU/mL | Standard Deviation 0.869 |
Secondary
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)
Time frame: Baseline, Week 48
Population: Participants with at least 12 weeks and 48 weeks of exposure to inarigivir soproxil and TAF, respectively, and with HBV DNA ≥ 69 IU/mL at Week 48 or Early Discontinuation were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1: Inarigivir Soproxil 50 mg + TAF | 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) | 4 Participants |
| Group 2: TAF | 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) | 0 Participants |
| Group 3: Inarigivir Soproxil 200 mg + TAF | 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) | 0 Participants |
| Group 5: Inarigivir Soproxil 400 mg + TAF | 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) | 4 Participants |
Secondary
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.
Time frame: Baseline, Weeks 12, 24, 36, and 48
Population: Participants in the Full Analysis Set (Group 4) with HBeAg-positive status at baseline were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1: Inarigivir Soproxil 50 mg + TAF | Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Group 4) | Week 12 | 14.3 percentage of participants |
| Group 1: Inarigivir Soproxil 50 mg + TAF | Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Group 4) | Week 24 | 14.3 percentage of participants |
| Group 1: Inarigivir Soproxil 50 mg + TAF | Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Group 4) | Week 36 | 14.3 percentage of participants |
| Group 1: Inarigivir Soproxil 50 mg + TAF | Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Group 4) | Week 48 | 14.3 percentage of participants |
Secondary
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.
Time frame: Baseline, Weeks 12, 24, 36, and 48
Population: Participants in the Full Analysis Set (Group 1-3 and 5) with HBeAg-positive status at baseline were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1: Inarigivir Soproxil 50 mg + TAF | Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 12 | 5.6 percentage of participants |
| Group 1: Inarigivir Soproxil 50 mg + TAF | Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 24 | 5.6 percentage of participants |
| Group 1: Inarigivir Soproxil 50 mg + TAF | Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 36 | 5.6 percentage of participants |
| Group 1: Inarigivir Soproxil 50 mg + TAF | Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 48 | 0 percentage of participants |
| Group 2: TAF | Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 24 | 0 percentage of participants |
| Group 2: TAF | Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 36 | 0 percentage of participants |
| Group 2: TAF | Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 48 | 0 percentage of participants |
| Group 2: TAF | Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 12 | 0 percentage of participants |
| Group 3: Inarigivir Soproxil 200 mg + TAF | Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 36 | 0 percentage of participants |
| Group 3: Inarigivir Soproxil 200 mg + TAF | Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 24 | 0 percentage of participants |
| Group 3: Inarigivir Soproxil 200 mg + TAF | Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 48 | 0 percentage of participants |
| Group 3: Inarigivir Soproxil 200 mg + TAF | Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 12 | 0 percentage of participants |
| Group 5: Inarigivir Soproxil 400 mg + TAF | Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 48 | 0 percentage of participants |
| Group 5: Inarigivir Soproxil 400 mg + TAF | Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 24 | 0 percentage of participants |
| Group 5: Inarigivir Soproxil 400 mg + TAF | Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 12 | 0 percentage of participants |
| Group 5: Inarigivir Soproxil 400 mg + TAF | Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 36 | 0 percentage of participants |
Secondary
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
Time frame: Baseline up to Week 12
Population: Participants in the Full Analysis Set (Group 4) were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: Inarigivir Soproxil 50 mg + TAF | Percentage of Participants Experiencing Hepatitis B Virus (HBV) Virologic Breakthrough During 12 Weeks of Inarigivir Soproxil Treatment (Group 4) | 0 percentage of participants |
Secondary
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.
Time frame: Baseline, Weeks 12, 24, 36, and 48
Population: Participants in the Full Analysis Set (Group 4) were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1: Inarigivir Soproxil 50 mg + TAF | Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Group 4) | Week 12 | 0 percentage of participants |
| Group 1: Inarigivir Soproxil 50 mg + TAF | Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Group 4) | Week 24 | 0 percentage of participants |
| Group 1: Inarigivir Soproxil 50 mg + TAF | Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Group 4) | Week 36 | 0 percentage of participants |
| Group 1: Inarigivir Soproxil 50 mg + TAF | Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Group 4) | Week 48 | 0 percentage of participants |
Secondary
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.
Time frame: Baseline, Weeks 12, 24, 36, and 48
Population: Participants in the Full Analysis Set (Groups 1 through 3 and 5) were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1: Inarigivir Soproxil 50 mg + TAF | Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 48 | 0 percentage of participants |
| Group 1: Inarigivir Soproxil 50 mg + TAF | Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 12 | 0 percentage of participants |
| Group 1: Inarigivir Soproxil 50 mg + TAF | Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 24 | 0 percentage of participants |
| Group 1: Inarigivir Soproxil 50 mg + TAF | Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 36 | 0 percentage of participants |
| Group 2: TAF | Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 24 | 0 percentage of participants |
| Group 2: TAF | Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 48 | 0 percentage of participants |
| Group 2: TAF | Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 36 | 0 percentage of participants |
| Group 2: TAF | Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 12 | 0 percentage of participants |
| Group 3: Inarigivir Soproxil 200 mg + TAF | Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 24 | 0 percentage of participants |
| Group 3: Inarigivir Soproxil 200 mg + TAF | Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 12 | 0 percentage of participants |
| Group 3: Inarigivir Soproxil 200 mg + TAF | Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 36 | 0 percentage of participants |
| Group 3: Inarigivir Soproxil 200 mg + TAF | Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 48 | 0 percentage of participants |
| Group 5: Inarigivir Soproxil 400 mg + TAF | Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 36 | 0 percentage of participants |
| Group 5: Inarigivir Soproxil 400 mg + TAF | Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 12 | 0 percentage of participants |
| Group 5: Inarigivir Soproxil 400 mg + TAF | Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 24 | 0 percentage of participants |
| Group 5: Inarigivir Soproxil 400 mg + TAF | Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) | Week 48 | 0 percentage of participants |
Secondary
Percentage of Participants With ≥ 1 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Group 4)
Time frame: Baseline, Week 12
Population: Participants in the Full Analysis Set (Group 4) were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: Inarigivir Soproxil 50 mg + TAF | Percentage of Participants With ≥ 1 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Group 4) | 0 percentage of participants |
Secondary
Percentage of Participants With ≥ 1 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Groups 1 Through 3 and 5)
Time frame: Baseline, Week 12
Population: Participants in the Full Analysis Set (Group 1-3 and 5) were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: Inarigivir Soproxil 50 mg + TAF | Percentage of Participants With ≥ 1 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Groups 1 Through 3 and 5) | 0 percentage of participants |
| Group 2: TAF | Percentage of Participants With ≥ 1 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Groups 1 Through 3 and 5) | 16.7 percentage of participants |
| Group 3: Inarigivir Soproxil 200 mg + TAF | Percentage of Participants With ≥ 1 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Groups 1 Through 3 and 5) | 0 percentage of participants |
| Group 5: Inarigivir Soproxil 400 mg + TAF | Percentage of Participants With ≥ 1 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Groups 1 Through 3 and 5) | 0 percentage of participants |
95% CI: [-37.7, 4.4]
95% CI: [-38.1, 4.3]
95% CI: [-37.9, 4.4]