Chronic Hepatitis B
Conditions
Keywords
HBV, Hepatitis, Liver Disease
Brief summary
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.
Interventions
DRUGTDF
300 mg tablets administered orally once daily
DRUGVesatolimod
Tablets administered orally once a week (every 7 days) for 12 doses
DRUGPlacebo
Placebo administered orally once a week (every 7 days) for 12 doses
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change (Measured in log10 IU/mL) in Hepatitis B Surface Antigen (HBsAg) From Baseline at Week 24 | Baseline; 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HBeAg Loss and Seroconversion at Week 48 | 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. |
| Percentage of Participants With HBsAg Loss and Seroconversion at Week 24 | 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. |
| Percentage of Participants With HBsAg Loss and Seroconversion at Week 48 | 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. |
| 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 | Baseline to 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. |
| Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 24 | Baseline to 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. |
| Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 48 | Baseline to 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. |
| Percentage of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantitation (LLOQ) at Week 24 | Week 24 | LLOQ for HBV DNA was defined as 20 IU/mL. The participants with missing information were excluded from the analysis. |
| Percentage of Participants With HBV DNA < LLOQ at Week 48 | Week 48 | LLOQ for HBV DNA was defined as 20 IU/mL. The participants with missing information were excluded from the analysis. |
| Percentage of Participants With HBeAg Loss and Seroconversion at Week 24 | 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. |
| Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase/Reverse Transcriptase (Pol/RT) | Baseline; Week 48 | 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. |
| Pharmacokinetic (PK) Parameter: AUClast of Vesatolimod | Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose | AUClast is defined as the area under the concentration versus time curve from time zero to the last quantifiable concentration. |
| PK Parameter: AUCinf of Vesatolimod | Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose | AUCinf is defined as the concentration of drug extrapolated to infinite time. |
| PK Parameter: %AUCexp of Vesatolimod | Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose | %AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf. |
| PK Parameter: Cmax of Vesatolimod | Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose | Cmax is defined as the maximum concentration of drug. |
| PK Parameter: Clast of Vesatolimod | Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose | Clast is defined as the last observable concentration of drug. |
| PK Parameter: Tmax of Vesatolimod | Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose | Tmax is defined as the time (observed time point) of Cmax |
| PK Parameter: Tlast of Vesatolimod | Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose | Tlast is defined as the time (observed time point) of Clast. |
| PK Parameter: T1/2 of Vesatolimod | Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose | T1/2 is defined as the estimate of the terminal elimination half-life of the drug. |
| PK Parameter: CL/F of Vesatolimod | Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose | CL/F is defined as the apparent oral clearance following administration of the drug. |
| Percentage of Participants Experiencing Virologic Breakthrough | Weeks 24 and 48 | 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. |
Countries
Canada, Hong Kong, Italy, New Zealand, South Korea, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in Asia, Europe, New Zealand, and North America. The first participant was screened on 10 November 2015. The last study visit occurred on 03 May 2019.
Pre-assignment details
260 participants were screened
Participants by arm
| Arm | Count |
|---|---|
| TDF + Placebo Main Study Phase: 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. | 28 |
| TDF + Vesatolimod 1 mg 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. | 53 |
| TDF + Vesatolimod 2 mg 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. | 56 |
| TDF + Vesatolimod 4 mg 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. | 55 |
| Total | 192 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Main Study Phase | Lack of Efficacy | 0 | 0 | 0 | 1 |
| Main Study Phase | Lost to Follow-up | 0 | 0 | 2 | 0 |
| Main Study Phase | Withdrew Consent | 0 | 0 | 0 | 2 |
| Optional Treatment Extension Phase(OTEP) | Adverse Event | 0 | 1 | 0 | 0 |
| Optional Treatment Extension Phase(OTEP) | Investigator's discretion | 1 | 0 | 2 | 0 |
| Optional Treatment Extension Phase(OTEP) | Lost to Follow-up | 0 | 1 | 1 | 1 |
| Optional Treatment Extension Phase(OTEP) | Non-compliance with Study Drug | 0 | 1 | 0 | 0 |
| Optional Treatment Extension Phase(OTEP) | Pregnancy | 0 | 1 | 0 | 0 |
| Optional Treatment Extension Phase(OTEP) | Withdrew Consent | 0 | 3 | 1 | 4 |
Baseline characteristics
| Characteristic | TDF + Vesatolimod 1 mg | TDF + Vesatolimod 2 mg | TDF + Vesatolimod 4 mg | TDF + Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 41 years STANDARD_DEVIATION 9.6 | 44 years STANDARD_DEVIATION 10.3 | 44 years STANDARD_DEVIATION 10.3 | 41 years STANDARD_DEVIATION 10.4 | 42 years STANDARD_DEVIATION 10.1 |
| Hepatitis B Envelope Antigen (HBeAg) Status HBeAg Status- Negative | 33 Participants | 33 Participants | 34 Participants | 17 Participants | 117 Participants |
| Hepatitis B Envelope Antigen (HBeAg) Status HBeAg Status- Positive | 20 Participants | 23 Participants | 21 Participants | 11 Participants | 75 Participants |
| Hepatitis B Virus (HBV) DNA | 5.9 log10 IU/mL STANDARD_DEVIATION 1.8 | 5.6 log10 IU/mL STANDARD_DEVIATION 1.85 | 5.9 log10 IU/mL STANDARD_DEVIATION 1.7 | 5.9 log10 IU/mL STANDARD_DEVIATION 2.1 | 5.8 log10 IU/mL STANDARD_DEVIATION 1.82 |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 53 Participants | 56 Participants | 55 Participants | 28 Participants | 192 Participants |
| Race/Ethnicity, Customized Ethnicity Not Permitted | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 41 Participants | 48 Participants | 44 Participants | 22 Participants | 155 Participants |
| Race/Ethnicity, Customized Race Black or African American | 5 Participants | 3 Participants | 0 Participants | 1 Participants | 9 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 6 Participants | 5 Participants | 10 Participants | 4 Participants | 25 Participants |
| Region of Enrollment Canada | 8 participants | 9 participants | 4 participants | 2 participants | 23 participants |
| Region of Enrollment Hong Kong | 3 participants | 0 participants | 2 participants | 0 participants | 5 participants |
| Region of Enrollment Italy | 8 participants | 6 participants | 12 participants | 6 participants | 32 participants |
| Region of Enrollment New Zealand | 0 participants | 1 participants | 3 participants | 1 participants | 5 participants |
| Region of Enrollment South Korea | 12 participants | 17 participants | 15 participants | 7 participants | 51 participants |
| Region of Enrollment Taiwan | 4 participants | 6 participants | 6 participants | 5 participants | 21 participants |
| Region of Enrollment United Kingdom | 4 participants | 4 participants | 3 participants | 1 participants | 12 participants |
| Region of Enrollment United States | 14 participants | 13 participants | 10 participants | 6 participants | 43 participants |
| Serum Hepatitis B Surface Antigen (HBsAg) (log10 IU/mL) | 3.7 log10 IU/mL STANDARD_DEVIATION 0.84 | 3.5 log10 IU/mL STANDARD_DEVIATION 0.88 | 3.6 log10 IU/mL STANDARD_DEVIATION 0.74 | 3.8 log10 IU/mL STANDARD_DEVIATION 0.84 | 3.6 log10 IU/mL STANDARD_DEVIATION 0.82 |
| Sex: Female, Male Female | 21 Participants | 16 Participants | 20 Participants | 12 Participants | 69 Participants |
| Sex: Female, Male Male | 32 Participants | 40 Participants | 35 Participants | 16 Participants | 123 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 53 | 0 / 56 | 0 / 55 | 0 / 27 | 0 / 51 | 0 / 54 | 0 / 49 |
| other Total, other adverse events | 14 / 28 | 25 / 53 | 27 / 56 | 33 / 55 | 7 / 27 | 14 / 51 | 13 / 54 | 12 / 49 |
| serious Total, serious adverse events | 0 / 28 | 1 / 53 | 1 / 56 | 1 / 55 | 1 / 27 | 4 / 51 | 5 / 54 | 1 / 49 |
Outcome results
Primary
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
Population: The Full Analysis Set included all participants who were randomized and took at least 1 dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| TDF + Placebo | Mean Change (Measured in log10 IU/mL) in Hepatitis B Surface Antigen (HBsAg) From Baseline at Week 24 | -0.163 log10 IU/mL |
| TDF + Vesatolimod 1 mg | Mean Change (Measured in log10 IU/mL) in Hepatitis B Surface Antigen (HBsAg) From Baseline at Week 24 | -0.056 log10 IU/mL |
| TDF + Vesatolimod 2 mg | Mean Change (Measured in log10 IU/mL) in Hepatitis B Surface Antigen (HBsAg) From Baseline at Week 24 | -0.146 log10 IU/mL |
| TDF + Vesatolimod 4 mg | Mean Change (Measured in log10 IU/mL) in Hepatitis B Surface Antigen (HBsAg) From Baseline at Week 24 | -0.036 log10 IU/mL |
p-value: 0.22795% CI: [-0.067, 0.282]MMRM
p-value: 0.8495% CI: [-0.156, 0.191]MMRM
p-value: 0.15195% CI: [-0.047, 0.301]MMRM
Secondary
Mean Change (Measured in log10 IU/mL) in HBsAg From Baseline at Week 12
Time frame: Baseline; Week 12
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TDF + Placebo | Mean Change (Measured in log10 IU/mL) in HBsAg From Baseline at Week 12 | -0.087 log10 IU/mL | Standard Deviation 0.2199 |
| TDF + Vesatolimod 1 mg | Mean Change (Measured in log10 IU/mL) in HBsAg From Baseline at Week 12 | -0.041 log10 IU/mL | Standard Deviation 0.2283 |
| TDF + Vesatolimod 2 mg | Mean Change (Measured in log10 IU/mL) in HBsAg From Baseline at Week 12 | -0.138 log10 IU/mL | Standard Deviation 0.5247 |
| TDF + Vesatolimod 4 mg | Mean Change (Measured in log10 IU/mL) in HBsAg From Baseline at Week 12 | -0.020 log10 IU/mL | Standard Deviation 0.2668 |
Secondary
Mean Change (Measured in log10 IU/mL) in HBsAg From Baseline at Week 48
Time frame: Baseline; Week 48
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TDF + Placebo | Mean Change (Measured in log10 IU/mL) in HBsAg From Baseline at Week 48 | -0.338 log10 IU/mL | Standard Deviation 0.8922 |
| TDF + Vesatolimod 1 mg | Mean Change (Measured in log10 IU/mL) in HBsAg From Baseline at Week 48 | -0.079 log10 IU/mL | Standard Deviation 0.2912 |
| TDF + Vesatolimod 2 mg | Mean Change (Measured in log10 IU/mL) in HBsAg From Baseline at Week 48 | -0.197 log10 IU/mL | Standard Deviation 0.5757 |
| TDF + Vesatolimod 4 mg | Mean Change (Measured in log10 IU/mL) in HBsAg From Baseline at Week 48 | -0.088 log10 IU/mL | Standard Deviation 0.37 |
Secondary
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
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TDF + Placebo | Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase/Reverse Transcriptase (Pol/RT) | 2 Participants |
| TDF + Vesatolimod 1 mg | Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase/Reverse Transcriptase (Pol/RT) | 4 Participants |
| TDF + Vesatolimod 2 mg | Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase/Reverse Transcriptase (Pol/RT) | 2 Participants |
| TDF + Vesatolimod 4 mg | Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase/Reverse Transcriptase (Pol/RT) | 2 Participants |
Secondary
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
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TDF + Placebo | Percentage of Participants Experiencing Virologic Breakthrough | Week 24 | 0 percentage of participants |
| TDF + Placebo | Percentage of Participants Experiencing Virologic Breakthrough | Week 48 | 0 percentage of participants |
| TDF + Vesatolimod 1 mg | Percentage of Participants Experiencing Virologic Breakthrough | Week 48 | 3.8 percentage of participants |
| TDF + Vesatolimod 1 mg | Percentage of Participants Experiencing Virologic Breakthrough | Week 24 | 0 percentage of participants |
| TDF + Vesatolimod 2 mg | Percentage of Participants Experiencing Virologic Breakthrough | Week 24 | 1.8 percentage of participants |
| TDF + Vesatolimod 2 mg | Percentage of Participants Experiencing Virologic Breakthrough | Week 48 | 1.8 percentage of participants |
| TDF + Vesatolimod 4 mg | Percentage of Participants Experiencing Virologic Breakthrough | Week 24 | 0 percentage of participants |
| TDF + Vesatolimod 4 mg | Percentage of Participants Experiencing Virologic Breakthrough | Week 48 | 0 percentage of participants |
Secondary
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
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF + Placebo | Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 12 | 7.1 percentage of participants |
| TDF + Vesatolimod 1 mg | Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 12 | 3.8 percentage of participants |
| TDF + Vesatolimod 2 mg | Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 12 | 10.7 percentage of participants |
| TDF + Vesatolimod 4 mg | Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 12 | 1.8 percentage of participants |
Secondary
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
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF + Placebo | Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 24 | 10.7 percentage of participants |
| TDF + Vesatolimod 1 mg | Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 24 | 3.8 percentage of participants |
| TDF + Vesatolimod 2 mg | Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 24 | 10.7 percentage of participants |
| TDF + Vesatolimod 4 mg | Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 24 | 3.6 percentage of participants |
Secondary
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
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF + Placebo | Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 48 | 17.9 percentage of participants |
| TDF + Vesatolimod 1 mg | Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 48 | 5.7 percentage of participants |
| TDF + Vesatolimod 2 mg | Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 48 | 16.1 percentage of participants |
| TDF + Vesatolimod 4 mg | Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 48 | 14.5 percentage of participants |
Secondary
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
Population: Participants in the Full Analysis Set who were HBeAg positive at baseline were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF + Placebo | Percentage of Participants With HBeAg Loss and Seroconversion at Week 24 | 0 percentage of participants |
| TDF + Vesatolimod 1 mg | Percentage of Participants With HBeAg Loss and Seroconversion at Week 24 | 0 percentage of participants |
| TDF + Vesatolimod 2 mg | Percentage of Participants With HBeAg Loss and Seroconversion at Week 24 | 0 percentage of participants |
| TDF + Vesatolimod 4 mg | Percentage of Participants With HBeAg Loss and Seroconversion at Week 24 | 0 percentage of participants |
Secondary
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
Population: Participants in the Full Analysis Set who were HBeAg positive at baseline were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF + Placebo | Percentage of Participants With HBeAg Loss and Seroconversion at Week 48 | 0 percentage of participants |
| TDF + Vesatolimod 1 mg | Percentage of Participants With HBeAg Loss and Seroconversion at Week 48 | 5.0 percentage of participants |
| TDF + Vesatolimod 2 mg | Percentage of Participants With HBeAg Loss and Seroconversion at Week 48 | 4.3 percentage of participants |
| TDF + Vesatolimod 4 mg | Percentage of Participants With HBeAg Loss and Seroconversion at Week 48 | 4.8 percentage of participants |
Secondary
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.
Time frame: Week 24
Population: Participants in the Full Analysis Set who were HBsAg positive at baseline were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF + Placebo | Percentage of Participants With HBsAg Loss and Seroconversion at Week 24 | 0 percentage of participants |
| TDF + Vesatolimod 1 mg | Percentage of Participants With HBsAg Loss and Seroconversion at Week 24 | 0 percentage of participants |
| TDF + Vesatolimod 2 mg | Percentage of Participants With HBsAg Loss and Seroconversion at Week 24 | 0 percentage of participants |
| TDF + Vesatolimod 4 mg | Percentage of Participants With HBsAg Loss and Seroconversion at Week 24 | 0 percentage of participants |
Secondary
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
Population: Participants in the Full Analysis Set who were HBsAg positive at baseline were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF + Placebo | Percentage of Participants With HBsAg Loss and Seroconversion at Week 48 | 0 percentage of participants |
| TDF + Vesatolimod 1 mg | Percentage of Participants With HBsAg Loss and Seroconversion at Week 48 | 0 percentage of participants |
| TDF + Vesatolimod 2 mg | Percentage of Participants With HBsAg Loss and Seroconversion at Week 48 | 0 percentage of participants |
| TDF + Vesatolimod 4 mg | Percentage of Participants With HBsAg Loss and Seroconversion at Week 48 | 0 percentage of participants |
Secondary
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
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF + Placebo | Percentage of Participants With HBV DNA < LLOQ at Week 48 | 64.3 percentage of participants |
| TDF + Vesatolimod 1 mg | Percentage of Participants With HBV DNA < LLOQ at Week 48 | 62.3 percentage of participants |
| TDF + Vesatolimod 2 mg | Percentage of Participants With HBV DNA < LLOQ at Week 48 | 75.9 percentage of participants |
| TDF + Vesatolimod 4 mg | Percentage of Participants With HBV DNA < LLOQ at Week 48 | 75.5 percentage of participants |
Secondary
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
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF + Placebo | Percentage of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantitation (LLOQ) at Week 24 | 53.6 percentage of participants |
| TDF + Vesatolimod 1 mg | Percentage of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantitation (LLOQ) at Week 24 | 58.5 percentage of participants |
| TDF + Vesatolimod 2 mg | Percentage of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantitation (LLOQ) at Week 24 | 59.3 percentage of participants |
| TDF + Vesatolimod 4 mg | Percentage of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantitation (LLOQ) at Week 24 | 63.0 percentage of participants |
Secondary
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.
Time frame: Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
Population: The PK Substudy Analysis Set included all randomized participants who took at least 1 dose of vesatolimod, participated in the PK substudy, and had at least 1 non-missing steady state PK parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TDF + Placebo | Pharmacokinetic (PK) Parameter: AUClast of Vesatolimod | 5252.3 hour*picogram/milliliter (h*pg/mL) | Standard Deviation 5756.26 |
| TDF + Vesatolimod 1 mg | Pharmacokinetic (PK) Parameter: AUClast of Vesatolimod | 7170.6 hour*picogram/milliliter (h*pg/mL) | Standard Deviation 4569.83 |
| TDF + Vesatolimod 2 mg | Pharmacokinetic (PK) Parameter: AUClast of Vesatolimod | 28537.2 hour*picogram/milliliter (h*pg/mL) | Standard Deviation 23608.94 |
Secondary
PK Parameter: %AUCexp of Vesatolimod
%AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf.
Time frame: Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
Population: Participants in the PK Substudy Analysis Set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TDF + Placebo | PK Parameter: %AUCexp of Vesatolimod | 31.1 Percentage of AUC | Standard Deviation 19.7 |
| TDF + Vesatolimod 1 mg | PK Parameter: %AUCexp of Vesatolimod | 28.6 Percentage of AUC | Standard Deviation 11.42 |
| TDF + Vesatolimod 2 mg | PK Parameter: %AUCexp of Vesatolimod | 19.3 Percentage of AUC | Standard Deviation 6.15 |
Secondary
PK Parameter: AUCinf of Vesatolimod
AUCinf is defined as the concentration of drug extrapolated to infinite time.
Time frame: Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TDF + Placebo | PK Parameter: AUCinf of Vesatolimod | 7277.3 h*pg/mL | Standard Deviation 6550.71 |
| TDF + Vesatolimod 1 mg | PK Parameter: AUCinf of Vesatolimod | 10239.0 h*pg/mL | Standard Deviation 6243.75 |
| TDF + Vesatolimod 2 mg | PK Parameter: AUCinf of Vesatolimod | 34534.8 h*pg/mL | Standard Deviation 26482.89 |
Secondary
PK Parameter: Clast of Vesatolimod
Clast is defined as the last observable concentration of drug.
Time frame: Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
Population: Participants in the PK Substudy Analysis Set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TDF + Placebo | PK Parameter: Clast of Vesatolimod | 92.8 pg/mL | Standard Deviation 73.8 |
| TDF + Vesatolimod 1 mg | PK Parameter: Clast of Vesatolimod | 119.0 pg/mL | Standard Deviation 74.45 |
| TDF + Vesatolimod 2 mg | PK Parameter: Clast of Vesatolimod | 328.0 pg/mL | Standard Deviation 165.19 |
Secondary
PK Parameter: CL/F of Vesatolimod
CL/F is defined as the apparent oral clearance following administration of the drug.
Time frame: Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
Population: Participants in the PK Substudy Analysis Set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TDF + Placebo | PK Parameter: CL/F of Vesatolimod | 273.9 liter/hour | Standard Deviation 270.58 |
| TDF + Vesatolimod 1 mg | PK Parameter: CL/F of Vesatolimod | 262.3 liter/hour | Standard Deviation 144.45 |
| TDF + Vesatolimod 2 mg | PK Parameter: CL/F of Vesatolimod | 156.2 liter/hour | Standard Deviation 72.48 |
Secondary
PK Parameter: Cmax of Vesatolimod
Cmax is defined as the maximum concentration of drug.
Time frame: Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
Population: Participants in the PK Substudy Analysis Set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TDF + Placebo | PK Parameter: Cmax of Vesatolimod | 667.8 picogram/milliliter (pg/mL) | Standard Deviation 785.44 |
| TDF + Vesatolimod 1 mg | PK Parameter: Cmax of Vesatolimod | 850.4 picogram/milliliter (pg/mL) | Standard Deviation 569.75 |
| TDF + Vesatolimod 2 mg | PK Parameter: Cmax of Vesatolimod | 4957.5 picogram/milliliter (pg/mL) | Standard Deviation 5035.46 |
Secondary
PK Parameter: T1/2 of Vesatolimod
T1/2 is defined as the estimate of the terminal elimination half-life of the drug.
Time frame: Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
Population: Participants in the PK Substudy Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TDF + Placebo | PK Parameter: T1/2 of Vesatolimod | 10.79 hours |
| TDF + Vesatolimod 1 mg | PK Parameter: T1/2 of Vesatolimod | 14.12 hours |
| TDF + Vesatolimod 2 mg | PK Parameter: T1/2 of Vesatolimod | 13.32 hours |
Secondary
PK Parameter: Tlast of Vesatolimod
Tlast is defined as the time (observed time point) of Clast.
Time frame: Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
Population: Participants in the PK Substudy Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TDF + Placebo | PK Parameter: Tlast of Vesatolimod | 24.00 hours |
| TDF + Vesatolimod 1 mg | PK Parameter: Tlast of Vesatolimod | 24.00 hours |
| TDF + Vesatolimod 2 mg | PK Parameter: Tlast of Vesatolimod | 24.00 hours |
Secondary
PK Parameter: Tmax of Vesatolimod
Tmax is defined as the time (observed time point) of Cmax
Time frame: Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
Population: Participants in the PK Substudy Analysis Set were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TDF + Placebo | PK Parameter: Tmax of Vesatolimod | 1.00 hours |
| TDF + Vesatolimod 1 mg | PK Parameter: Tmax of Vesatolimod | 2.00 hours |
| TDF + Vesatolimod 2 mg | PK Parameter: Tmax of Vesatolimod | 3.00 hours |