Chronic Hepatitis B
Conditions
Keywords
Hepatitis B, HBV, GS-9620, TLR-7 Agonist
Brief summary
The primary objectives of this study are to evaluate the safety, tolerability, and efficacy of vesatolimod in participants with chronic hepatitis B (CHB) infection currently being treated with oral antivirals (OAV). Participants will be randomized in 3 sequential cohorts (Cohorts A, B, and C). Within each cohort, participants will be randomized in a 1:3:3:3 ratio to placebo or one of the doses of vesatolimod (1, 2, or 4 mg).
Interventions
DRUGVesatolimod
Vesatolimod tablet administered orally
DRUGPlacebo
Placebo to match vesatolimod tablet administered orally
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Must have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures * Documented evidence of CHB infection (eg, hepatitis B surface antigen \[HBsAg\] positive for more than 6 months) with detectable HBsAg levels at screening * Have been on approved HBV OAV treatment for ≥ 1 year prior to screening, with HBV DNA below lower limit of quantitation (LLOQ), measured at least once, 6 or more months prior to screening, and HBV DNA \< 20 IU/mL at screening * Currently taking an approved HBV OAV (tenofovir, entecavir, adefovir, lamivudine, or telbivudine, either as single agents or in combination) with no change in regimen for 3 months prior to screening * Willing to provide blood sample for toll-like receptor 7 (TLR-7) and interleukin 28 B (IL28B) single-nucleotide polymorphism (SNP) assessment * Must be willing and able to comply with all study requirements Key
Exclusion criteria
* Extensive bridging fibrosis or cirrhosis * Laboratory parameters not within defined thresholds for neutropenia, anemia, thrombocytopenia, leukopenia, or other evidence of inadequate liver function * Coinfection with hepatitis C virus (HCV), HIV, or hepatitis D virus (HDV) * Evidence of hepatocellular carcinoma * Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc.). Participants under evaluation for possible malignancy are not eligible. * Significant cardiovascular, pulmonary, or neurological disease * Any of the following conditions that may worsen in response to interferon (IFN): * Autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, sarcoidosis, moderate or severe psoriasis) * Poorly controlled diabetes mellitus * Significant psychiatric disorders * Thyroid disorder (unless controlled under treatment) * Significant pulmonary diseases (eg, chronic obstructive pulmonary disease) * Retinal disease * Immunodeficiency disorders * Received solid organ or bone marrow transplant * Received prolonged therapy with immunomodulators (eg, corticosteroids) or biologics (eg, monoclonal Ab, interferon) within 3 months of screening * Use of another investigational agents within 3 months of screening * Current alcohol or substance abuse judged by the investigator to potentially interfere with compliance * Females who are pregnant or may wish to become pregnant during the study Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Level at Week 24 | Baseline to Week 24 | A mixed effect model for repeated measures (MMRM) was used to analyze HBsAg change from baseline, which included treatment, baseline HBsAg level (\> 5000 IU/mL or ≤ 5000 IU/mL), HBeAg baseline status (positive or negative), visit and treatment-by-visit interaction as fixed effect and visit as repeated measurement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (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 within the targeted time window. HBeAg seroconversion was defined as qualitative hepatitis B envelope antibody (HBeAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window. Participants who had missing information were assumed to have no HBeAg loss and no HBeAg seroconversion. Only participants who were HBeAg+ at baseline were included. |
| Composite Endpoint Measuring the 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 within the targeted time window. HBsAg seroconversion was defined as qualitative hepatitis B surface antibody (HBsAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window. Participants who had missing information were assumed to have no HBsAg loss and no HBsAg seroconversion. |
| Composite Endpoint Measuring the 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 within the targeted time window. HBsAg seroconversion was defined as qualitative hepatitis B surface antibody (HBsAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window. Participants who had missing information were assumed to have no HBsAg loss and no HBsAg seroconversion. |
| Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (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 within the targeted time window. HBeAg seroconversion was defined as qualitative hepatitis B envelope antibody (HBeAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window. Participants who had missing information were assumed to have no HBeAg loss and no HBeAg seroconversion. |
| Change From Baseline in Serum HBsAg Level at Week 8 | Baseline; Week 8 | — |
| Change From Baseline in Serum HBsAg Level at Week 12 | Baseline; Week 12 | — |
| Change From Baseline in Serum HBsAg Level at Week 48 | Baseline; Week 48 | — |
| Change From Baseline in Serum HBsAg Level at Week 4 | Baseline; Week 4 | — |
Countries
Canada, Italy, Netherlands, New Zealand, South Korea, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States, Canada, Italy, South Korea, The Netherlands, and New Zealand. The first participant was screened on 30 June 2014. The last study visit occurred on 20 October 2016.
Pre-assignment details
All participants continued their approved HBV oral antiviral therapy (tenofovir disoproxil fumarate (TDF), entecavir (ETV), adefovir, lamivudine, or telbivudine, either as single agents or in combination) throughout the study. 200 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Vesatolimod 1 mg 4 Weeks (Cohort A) Vesatolimod 1 mg tablet once a week for 4 weeks | 16 |
| Vesatolimod 2 mg 4 Weeks (Cohort A) Vesatolimod 2 mg tablet once a week for 4 weeks | 15 |
| Vesatolimod 4 mg 4 Weeks (Cohort A) Vesatolimod 4 mg tablet once a week for 4 weeks | 16 |
| Placebo 4 Weeks (Cohort A) Placebo tablet once a week for 4 weeks | 5 |
| Vesatolimod 1 mg 8 Weeks (Cohort B) Vesatolimod 1 mg tablet once a week for 8 weeks | 18 |
| Vesatolimod 2 mg 8 Weeks (Cohort B) Vesatolimod 2 mg tablet once a week for 8 weeks | 17 |
| Vesatolimod 4 mg 8 Weeks (Cohort B) Vesatolimod 4 mg tablet once a week for 8 weeks | 17 |
| Placebo 8 Weeks (Cohort B) Placebo tablet once a week for 8 weeks | 5 |
| Vesatolimod 1 mg 12 Weeks (Cohort C) Vesatolimod 1 mg tablet once a week for 12 weeks | 16 |
| Vesatolimod 2 mg 12 Weeks (Cohort C) Vesatolimod 2 mg tablet once a week for 12 weeks | 17 |
| Vesatolimod 4 mg 12 Weeks (Cohort C) Vesatolimod 4 mg tablet once a week for 12 weeks | 14 |
| Placebo 12 Weeks (Cohort C) Placebo tablet once a week for 12 weeks | 6 |
| Total | 162 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 2 | 0 |
| Overall Study | Withdrawal by Participant | 0 | 1 | 2 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Vesatolimod 2 mg 4 Weeks (Cohort A) | Vesatolimod 4 mg 4 Weeks (Cohort A) | Placebo 4 Weeks (Cohort A) | Vesatolimod 1 mg 8 Weeks (Cohort B) | Vesatolimod 2 mg 8 Weeks (Cohort B) | Vesatolimod 4 mg 8 Weeks (Cohort B) | Placebo 8 Weeks (Cohort B) | Vesatolimod 1 mg 12 Weeks (Cohort C) | Vesatolimod 2 mg 12 Weeks (Cohort C) | Vesatolimod 4 mg 12 Weeks (Cohort C) | Placebo 12 Weeks (Cohort C) | Vesatolimod 1 mg 4 Weeks (Cohort A) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 48 years STANDARD_DEVIATION 9.7 | 50 years STANDARD_DEVIATION 11.2 | 47 years STANDARD_DEVIATION 10 | 53 years STANDARD_DEVIATION 5.3 | 51 years STANDARD_DEVIATION 8.2 | 44 years STANDARD_DEVIATION 9 | 44 years STANDARD_DEVIATION 11.1 | 53 years STANDARD_DEVIATION 5.4 | 48 years STANDARD_DEVIATION 9.8 | 48 years STANDARD_DEVIATION 9.7 | 50 years STANDARD_DEVIATION 11.6 | 46 years STANDARD_DEVIATION 10.9 | 47 years STANDARD_DEVIATION 7.3 |
| Hepatitis B Envelope Antigen (HBeAg) Status Negative | 128 Participants | 11 Participants | 12 Participants | 4 Participants | 13 Participants | 14 Participants | 14 Participants | 5 Participants | 13 Participants | 14 Participants | 12 Participants | 4 Participants | 12 Participants |
| Hepatitis B Envelope Antigen (HBeAg) Status Positive | 34 Participants | 4 Participants | 4 Participants | 1 Participants | 5 Participants | 3 Participants | 3 Participants | 0 Participants | 3 Participants | 3 Participants | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Ethnicity: Not Hispanic or Latino | 162 Participants | 15 Participants | 16 Participants | 5 Participants | 18 Participants | 17 Participants | 17 Participants | 5 Participants | 16 Participants | 17 Participants | 14 Participants | 6 Participants | 16 Participants |
| Race/Ethnicity, Customized Race Asian | 117 Participants | 10 Participants | 12 Participants | 4 Participants | 15 Participants | 15 Participants | 16 Participants | 4 Participants | 9 Participants | 8 Participants | 9 Participants | 2 Participants | 13 Participants |
| Race/Ethnicity, Customized Race Black or African American | 3 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Pacific Islander | 34 Participants | 2 Participants | 3 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 7 Participants | 8 Participants | 5 Participants | 4 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race White | 7 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Region of Enrollment Canada | 33 Participants | 3 Participants | 3 Participants | 0 Participants | 4 Participants | 5 Participants | 2 Participants | 0 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 8 Participants |
| Region of Enrollment Italy | 28 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 9 Participants | 8 Participants | 9 Participants | 2 Participants | 0 Participants |
| Region of Enrollment Netherlands | 6 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment New Zealand | 24 Participants | 2 Participants | 6 Participants | 3 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 3 Participants | 2 Participants | 0 Participants | 0 Participants | 4 Participants |
| Region of Enrollment South Korea | 28 Participants | 0 Participants | 0 Participants | 0 Participants | 7 Participants | 4 Participants | 9 Participants | 3 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment United States | 43 Participants | 10 Participants | 7 Participants | 2 Participants | 3 Participants | 4 Participants | 5 Participants | 1 Participants | 1 Participants | 3 Participants | 2 Participants | 1 Participants | 4 Participants |
| Serum HBsAg Level Categories ≤ 5000 IU/mL | 139 Participants | 13 Participants | 13 Participants | 4 Participants | 15 Participants | 15 Participants | 14 Participants | 5 Participants | 14 Participants | 15 Participants | 13 Participants | 5 Participants | 13 Participants |
| Serum HBsAg Level Categories > 5000 IU/mL | 23 Participants | 2 Participants | 3 Participants | 1 Participants | 3 Participants | 2 Participants | 3 Participants | 0 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 3 Participants |
| Serum Hepatitis B Surface Antigen (HBsAg) Level | 3.0 log10 IU/mL STANDARD_DEVIATION 0.7 | 3.1 log10 IU/mL STANDARD_DEVIATION 0.59 | 3.0 log10 IU/mL STANDARD_DEVIATION 0.7 | 3.1 log10 IU/mL STANDARD_DEVIATION 0.69 | 3.1 log10 IU/mL STANDARD_DEVIATION 0.62 | 3.0 log10 IU/mL STANDARD_DEVIATION 0.69 | 3.1 log10 IU/mL STANDARD_DEVIATION 0.9 | 2.7 log10 IU/mL STANDARD_DEVIATION 0.73 | 3.3 log10 IU/mL STANDARD_DEVIATION 0.45 | 3.0 log10 IU/mL STANDARD_DEVIATION 0.54 | 3.0 log10 IU/mL STANDARD_DEVIATION 0.69 | 2.4 log10 IU/mL STANDARD_DEVIATION 1.01 | 2.8 log10 IU/mL STANDARD_DEVIATION 0.88 |
| Sex: Female, Male Female | 39 Participants | 5 Participants | 4 Participants | 1 Participants | 9 Participants | 4 Participants | 4 Participants | 1 Participants | 5 Participants | 2 Participants | 3 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 123 Participants | 10 Participants | 12 Participants | 4 Participants | 9 Participants | 13 Participants | 13 Participants | 4 Participants | 11 Participants | 15 Participants | 11 Participants | 6 Participants | 15 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 | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 15 | 0 / 16 | 0 / 5 | 0 / 18 | 0 / 17 | 0 / 17 | 0 / 5 | 0 / 16 | 0 / 17 | 0 / 14 | 0 / 6 |
| other Total, other adverse events | 10 / 16 | 12 / 15 | 13 / 16 | 4 / 5 | 12 / 18 | 7 / 17 | 10 / 17 | 4 / 5 | 12 / 16 | 12 / 17 | 9 / 14 | 3 / 6 |
| serious Total, serious adverse events | 0 / 16 | 1 / 15 | 1 / 16 | 0 / 5 | 0 / 18 | 0 / 17 | 0 / 17 | 0 / 5 | 0 / 16 | 1 / 17 | 1 / 14 | 0 / 6 |
Outcome results
Primary
Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Level at Week 24
A mixed effect model for repeated measures (MMRM) was used to analyze HBsAg change from baseline, which included treatment, baseline HBsAg level (\> 5000 IU/mL or ≤ 5000 IU/mL), HBeAg baseline status (positive or negative), visit and treatment-by-visit interaction as fixed effect and visit as repeated measurement.
Time frame: Baseline to Week 24
Population: Participants in the Full Analysis Set (participants who were randomized and received at least 1 dose of study drug) with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Vesatolimod 1 mg 4 Weeks (Cohort A) | Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Level at Week 24 | -0.011 log10 IU/mL |
| Vesatolimod 2 mg 4 Weeks (Cohort A) | Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Level at Week 24 | 0.033 log10 IU/mL |
| Vesatolimod 4 mg 4 Weeks (Cohort A) | Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Level at Week 24 | -0.018 log10 IU/mL |
| Placebo 4 Weeks (Cohort A) | Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Level at Week 24 | -0.035 log10 IU/mL |
| Vesatolimod 1 mg 8 Weeks (Cohort B) | Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Level at Week 24 | -0.081 log10 IU/mL |
| Vesatolimod 2 mg 8 Weeks (Cohort B) | Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Level at Week 24 | -0.081 log10 IU/mL |
| Vesatolimod 4 mg 8 Weeks (Cohort B) | Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Level at Week 24 | -0.082 log10 IU/mL |
| Placebo 8 Weeks (Cohort B) | Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Level at Week 24 | -0.163 log10 IU/mL |
| Vesatolimod 1 mg 12 Weeks (Cohort C) | Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Level at Week 24 | -0.015 log10 IU/mL |
| Vesatolimod 2 mg 12 Weeks (Cohort C) | Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Level at Week 24 | 0.000 log10 IU/mL |
| Vesatolimod 4 mg 12 Weeks (Cohort C) | Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Level at Week 24 | 0.000 log10 IU/mL |
| Placebo 12 Weeks (Cohort C) | Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Level at Week 24 | 0.001 log10 IU/mL |
p-value: 0.5995% CI: [-0.061, 0.108]MMRM
p-value: 0.1295% CI: [-0.018, 0.154]MMRM
p-value: 0.70195% CI: [-0.069, 0.102]MMRM
p-value: 0.2195% CI: [-0.046, 0.21]MMRM
p-value: 0.20795% CI: [-0.046, 0.21]MMRM
p-value: 0.21695% CI: [-0.048, 0.21]MMRM
p-value: 0.65295% CI: [-0.081, 0.051]MMRM
p-value: 0.99495% CI: [-0.066, 0.065]MMRM
p-value: 0.99695% CI: [-0.069, 0.069]MMRM
Secondary
Change From Baseline in Serum HBsAg Level 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 |
|---|---|---|---|
| Vesatolimod 1 mg 4 Weeks (Cohort A) | Change From Baseline in Serum HBsAg Level at Week 12 | -0.050 log10 IU/mL | Standard Deviation 0.0755 |
| Vesatolimod 2 mg 4 Weeks (Cohort A) | Change From Baseline in Serum HBsAg Level at Week 12 | 0.017 log10 IU/mL | Standard Deviation 0.0646 |
| Vesatolimod 4 mg 4 Weeks (Cohort A) | Change From Baseline in Serum HBsAg Level at Week 12 | -0.004 log10 IU/mL | Standard Deviation 0.0546 |
| Placebo 4 Weeks (Cohort A) | Change From Baseline in Serum HBsAg Level at Week 12 | -0.023 log10 IU/mL | Standard Deviation 0.0623 |
| Vesatolimod 1 mg 8 Weeks (Cohort B) | Change From Baseline in Serum HBsAg Level at Week 12 | -0.031 log10 IU/mL | Standard Deviation 0.0817 |
| Vesatolimod 2 mg 8 Weeks (Cohort B) | Change From Baseline in Serum HBsAg Level at Week 12 | -0.005 log10 IU/mL | Standard Deviation 0.0843 |
| Vesatolimod 4 mg 8 Weeks (Cohort B) | Change From Baseline in Serum HBsAg Level at Week 12 | -0.021 log10 IU/mL | Standard Deviation 0.0716 |
| Placebo 8 Weeks (Cohort B) | Change From Baseline in Serum HBsAg Level at Week 12 | -0.020 log10 IU/mL | Standard Deviation 0.0666 |
| Vesatolimod 1 mg 12 Weeks (Cohort C) | Change From Baseline in Serum HBsAg Level at Week 12 | -0.023 log10 IU/mL | Standard Deviation 0.0545 |
| Vesatolimod 2 mg 12 Weeks (Cohort C) | Change From Baseline in Serum HBsAg Level at Week 12 | -0.034 log10 IU/mL | Standard Deviation 0.0549 |
| Vesatolimod 4 mg 12 Weeks (Cohort C) | Change From Baseline in Serum HBsAg Level at Week 12 | -0.010 log10 IU/mL | Standard Deviation 0.0621 |
| Placebo 12 Weeks (Cohort C) | Change From Baseline in Serum HBsAg Level at Week 12 | -0.024 log10 IU/mL | Standard Deviation 0.0661 |
Secondary
Change From Baseline in Serum HBsAg Level at Week 4
Time frame: Baseline; Week 4
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vesatolimod 1 mg 4 Weeks (Cohort A) | Change From Baseline in Serum HBsAg Level at Week 4 | -0.009 log10 IU/mL | Standard Deviation 0.0505 |
| Vesatolimod 2 mg 4 Weeks (Cohort A) | Change From Baseline in Serum HBsAg Level at Week 4 | 0.025 log10 IU/mL | Standard Deviation 0.0514 |
| Vesatolimod 4 mg 4 Weeks (Cohort A) | Change From Baseline in Serum HBsAg Level at Week 4 | -0.008 log10 IU/mL | Standard Deviation 0.0516 |
| Placebo 4 Weeks (Cohort A) | Change From Baseline in Serum HBsAg Level at Week 4 | -0.017 log10 IU/mL | Standard Deviation 0.06 |
| Vesatolimod 1 mg 8 Weeks (Cohort B) | Change From Baseline in Serum HBsAg Level at Week 4 | -0.003 log10 IU/mL | Standard Deviation 0.0574 |
| Vesatolimod 2 mg 8 Weeks (Cohort B) | Change From Baseline in Serum HBsAg Level at Week 4 | 0.014 log10 IU/mL | Standard Deviation 0.0794 |
| Vesatolimod 4 mg 8 Weeks (Cohort B) | Change From Baseline in Serum HBsAg Level at Week 4 | -0.001 log10 IU/mL | Standard Deviation 0.0436 |
| Placebo 8 Weeks (Cohort B) | Change From Baseline in Serum HBsAg Level at Week 4 | 0.046 log10 IU/mL | Standard Deviation 0.0648 |
| Vesatolimod 1 mg 12 Weeks (Cohort C) | Change From Baseline in Serum HBsAg Level at Week 4 | -0.034 log10 IU/mL | Standard Deviation 0.0375 |
| Vesatolimod 2 mg 12 Weeks (Cohort C) | Change From Baseline in Serum HBsAg Level at Week 4 | -0.023 log10 IU/mL | Standard Deviation 0.0529 |
| Vesatolimod 4 mg 12 Weeks (Cohort C) | Change From Baseline in Serum HBsAg Level at Week 4 | -0.001 log10 IU/mL | Standard Deviation 0.0627 |
| Placebo 12 Weeks (Cohort C) | Change From Baseline in Serum HBsAg Level at Week 4 | -0.041 log10 IU/mL | Standard Deviation 0.0955 |
Secondary
Change From Baseline in Serum HBsAg Level 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 |
|---|---|---|---|
| Vesatolimod 1 mg 4 Weeks (Cohort A) | Change From Baseline in Serum HBsAg Level at Week 48 | -0.048 log10 IU/mL | Standard Deviation 0.1054 |
| Vesatolimod 2 mg 4 Weeks (Cohort A) | Change From Baseline in Serum HBsAg Level at Week 48 | -0.055 log10 IU/mL | Standard Deviation 0.14 |
| Vesatolimod 4 mg 4 Weeks (Cohort A) | Change From Baseline in Serum HBsAg Level at Week 48 | -0.071 log10 IU/mL | Standard Deviation 0.0857 |
| Placebo 4 Weeks (Cohort A) | Change From Baseline in Serum HBsAg Level at Week 48 | -0.067 log10 IU/mL | Standard Deviation 0.0831 |
| Vesatolimod 1 mg 8 Weeks (Cohort B) | Change From Baseline in Serum HBsAg Level at Week 48 | -0.035 log10 IU/mL | Standard Deviation 0.0923 |
| Vesatolimod 2 mg 8 Weeks (Cohort B) | Change From Baseline in Serum HBsAg Level at Week 48 | -0.024 log10 IU/mL | Standard Deviation 0.0679 |
| Vesatolimod 4 mg 8 Weeks (Cohort B) | Change From Baseline in Serum HBsAg Level at Week 48 | -0.114 log10 IU/mL | Standard Deviation 0.2169 |
| Placebo 8 Weeks (Cohort B) | Change From Baseline in Serum HBsAg Level at Week 48 | -0.324 log10 IU/mL | Standard Deviation 0.6811 |
| Vesatolimod 1 mg 12 Weeks (Cohort C) | Change From Baseline in Serum HBsAg Level at Week 48 | -0.083 log10 IU/mL | Standard Deviation 0.0858 |
| Vesatolimod 2 mg 12 Weeks (Cohort C) | Change From Baseline in Serum HBsAg Level at Week 48 | -0.071 log10 IU/mL | Standard Deviation 0.1076 |
| Vesatolimod 4 mg 12 Weeks (Cohort C) | Change From Baseline in Serum HBsAg Level at Week 48 | -0.054 log10 IU/mL | Standard Deviation 0.0715 |
| Placebo 12 Weeks (Cohort C) | Change From Baseline in Serum HBsAg Level at Week 48 | -0.063 log10 IU/mL | Standard Deviation 0.1011 |
Secondary
Change From Baseline in Serum HBsAg Level at Week 8
Time frame: Baseline; Week 8
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vesatolimod 1 mg 4 Weeks (Cohort A) | Change From Baseline in Serum HBsAg Level at Week 8 | -0.029 log10 IU/mL | Standard Deviation 0.0666 |
| Vesatolimod 2 mg 4 Weeks (Cohort A) | Change From Baseline in Serum HBsAg Level at Week 8 | 0.002 log10 IU/mL | Standard Deviation 0.0544 |
| Vesatolimod 4 mg 4 Weeks (Cohort A) | Change From Baseline in Serum HBsAg Level at Week 8 | -0.035 log10 IU/mL | Standard Deviation 0.0649 |
| Placebo 4 Weeks (Cohort A) | Change From Baseline in Serum HBsAg Level at Week 8 | -0.013 log10 IU/mL | Standard Deviation 0.044 |
| Vesatolimod 1 mg 8 Weeks (Cohort B) | Change From Baseline in Serum HBsAg Level at Week 8 | 0.000 log10 IU/mL | Standard Deviation 0.0442 |
| Vesatolimod 2 mg 8 Weeks (Cohort B) | Change From Baseline in Serum HBsAg Level at Week 8 | 0.006 log10 IU/mL | Standard Deviation 0.0772 |
| Vesatolimod 4 mg 8 Weeks (Cohort B) | Change From Baseline in Serum HBsAg Level at Week 8 | 0.020 log10 IU/mL | Standard Deviation 0.0596 |
| Placebo 8 Weeks (Cohort B) | Change From Baseline in Serum HBsAg Level at Week 8 | 0.006 log10 IU/mL | Standard Deviation 0.06 |
| Vesatolimod 1 mg 12 Weeks (Cohort C) | Change From Baseline in Serum HBsAg Level at Week 8 | -0.021 log10 IU/mL | Standard Deviation 0.0376 |
| Vesatolimod 2 mg 12 Weeks (Cohort C) | Change From Baseline in Serum HBsAg Level at Week 8 | -0.033 log10 IU/mL | Standard Deviation 0.0487 |
| Vesatolimod 4 mg 12 Weeks (Cohort C) | Change From Baseline in Serum HBsAg Level at Week 8 | -0.013 log10 IU/mL | Standard Deviation 0.0426 |
| Placebo 12 Weeks (Cohort C) | Change From Baseline in Serum HBsAg Level at Week 8 | -0.019 log10 IU/mL | Standard Deviation 0.0483 |
Secondary
Composite Endpoint Measuring the 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 within the targeted time window. HBsAg seroconversion was defined as qualitative hepatitis B surface antibody (HBsAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window. Participants who had missing information were assumed to have no HBsAg loss and no HBsAg seroconversion.
Time frame: Week 24
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vesatolimod 1 mg 4 Weeks (Cohort A) | Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 24 | 0 percentage of participants |
| Vesatolimod 2 mg 4 Weeks (Cohort A) | Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 24 | 0 percentage of participants |
| Vesatolimod 4 mg 4 Weeks (Cohort A) | Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 24 | 0 percentage of participants |
| Placebo 4 Weeks (Cohort A) | Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 24 | 0 percentage of participants |
| Vesatolimod 1 mg 8 Weeks (Cohort B) | Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 24 | 0 percentage of participants |
| Vesatolimod 2 mg 8 Weeks (Cohort B) | Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 24 | 0 percentage of participants |
| Vesatolimod 4 mg 8 Weeks (Cohort B) | Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 24 | 0 percentage of participants |
| Placebo 8 Weeks (Cohort B) | Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 24 | 0 percentage of participants |
| Vesatolimod 1 mg 12 Weeks (Cohort C) | Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 24 | 0 percentage of participants |
| Vesatolimod 2 mg 12 Weeks (Cohort C) | Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 24 | 0 percentage of participants |
| Vesatolimod 4 mg 12 Weeks (Cohort C) | Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 24 | 0 percentage of participants |
| Placebo 12 Weeks (Cohort C) | Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 24 | 0 percentage of participants |
Secondary
Composite Endpoint Measuring the 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 within the targeted time window. HBsAg seroconversion was defined as qualitative hepatitis B surface antibody (HBsAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window. Participants who had missing information were assumed to have no HBsAg loss and no HBsAg seroconversion.
Time frame: Week 48
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vesatolimod 1 mg 4 Weeks (Cohort A) | Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 48 | 0.0 percentage of participants |
| Vesatolimod 2 mg 4 Weeks (Cohort A) | Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 48 | 0.0 percentage of participants |
| Vesatolimod 4 mg 4 Weeks (Cohort A) | Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 48 | 0.0 percentage of participants |
| Placebo 4 Weeks (Cohort A) | Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 48 | 0.0 percentage of participants |
| Vesatolimod 1 mg 8 Weeks (Cohort B) | Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 48 | 0.0 percentage of participants |
| Vesatolimod 2 mg 8 Weeks (Cohort B) | Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 48 | 0.0 percentage of participants |
| Vesatolimod 4 mg 8 Weeks (Cohort B) | Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 48 | 0.0 percentage of participants |
| Placebo 8 Weeks (Cohort B) | Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 48 | 0.0 percentage of participants |
| Vesatolimod 1 mg 12 Weeks (Cohort C) | Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 48 | 0.0 percentage of participants |
| Vesatolimod 2 mg 12 Weeks (Cohort C) | Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 48 | 0.0 percentage of participants |
| Vesatolimod 4 mg 12 Weeks (Cohort C) | Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 48 | 0.0 percentage of participants |
| Placebo 12 Weeks (Cohort C) | Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 48 | 0.0 percentage of participants |
Secondary
Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (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 within the targeted time window. HBeAg seroconversion was defined as qualitative hepatitis B envelope antibody (HBeAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window. Participants who had missing information were assumed to have no HBeAg loss and no HBeAg seroconversion.
Time frame: Week 24
Population: Participants in the Full Analysis Set with HBeAg+ at Baseline were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vesatolimod 1 mg 4 Weeks (Cohort A) | Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 24 | 0.0 percentage of participants |
| Vesatolimod 2 mg 4 Weeks (Cohort A) | Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 24 | 0.0 percentage of participants |
| Vesatolimod 4 mg 4 Weeks (Cohort A) | Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 24 | 0.0 percentage of participants |
| Placebo 4 Weeks (Cohort A) | Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 24 | 0.0 percentage of participants |
| Vesatolimod 1 mg 8 Weeks (Cohort B) | Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 24 | 20.0 percentage of participants |
| Vesatolimod 2 mg 8 Weeks (Cohort B) | Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 24 | 0.0 percentage of participants |
| Vesatolimod 4 mg 8 Weeks (Cohort B) | Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 24 | 0.0 percentage of participants |
| Vesatolimod 1 mg 12 Weeks (Cohort C) | Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 24 | 0.0 percentage of participants |
| Vesatolimod 2 mg 12 Weeks (Cohort C) | Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 24 | 0.0 percentage of participants |
| Vesatolimod 4 mg 12 Weeks (Cohort C) | Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 24 | 0.0 percentage of participants |
| Placebo 12 Weeks (Cohort C) | Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 24 | 0.0 percentage of participants |
Secondary
Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (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 within the targeted time window. HBeAg seroconversion was defined as qualitative hepatitis B envelope antibody (HBeAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window. Participants who had missing information were assumed to have no HBeAg loss and no HBeAg seroconversion. Only participants who were HBeAg+ at baseline were included.
Time frame: Week 48
Population: Participants in the Full Analysis Set with HBeAg+ at Baseline were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vesatolimod 1 mg 4 Weeks (Cohort A) | Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 48 | 0.0 percentage of participants |
| Vesatolimod 2 mg 4 Weeks (Cohort A) | Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 48 | 0.0 percentage of participants |
| Vesatolimod 4 mg 4 Weeks (Cohort A) | Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 48 | 0.0 percentage of participants |
| Placebo 4 Weeks (Cohort A) | Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 48 | 0.0 percentage of participants |
| Vesatolimod 1 mg 8 Weeks (Cohort B) | Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 48 | 20.0 percentage of participants |
| Vesatolimod 2 mg 8 Weeks (Cohort B) | Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 48 | 0.0 percentage of participants |
| Vesatolimod 4 mg 8 Weeks (Cohort B) | Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 48 | 0.0 percentage of participants |
| Vesatolimod 1 mg 12 Weeks (Cohort C) | Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 48 | 33.3 percentage of participants |
| Vesatolimod 2 mg 12 Weeks (Cohort C) | Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 48 | 0.0 percentage of participants |
| Vesatolimod 4 mg 12 Weeks (Cohort C) | Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 48 | 0.0 percentage of participants |
| Placebo 12 Weeks (Cohort C) | Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 48 | 0.0 percentage of participants |