Chronic Hepatitis B
Conditions
Brief summary
The primary objectives of this study are to evaluate the safety and tolerability of multiple oral doses of selgantolimod and to evaluate the antiviral activity of selgantolimod in adult participants with chronic hepatitis B (CHB) who are viremic and not currently being treated.
Interventions
DRUGPlacebo
Tablet(s) administered orally every 7 days for 24 doses in fasted state
DRUGSelgantolimod
Tablet(s) administered orally every 7 days for 24 doses in fasted state
DRUGTAF
Tablet(s) administered orally once daily with food
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: * Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures. * Adult male and non-pregnant, non-lactating females * Documented evidence of chronic hepatitis B virus (HBV) infection with detectable hepatitis B surface antigen (HBsAg) levels at screening * Screening HBV deoxyribonucleic acid (DNA) ≥ 2000 international units per milliliter (IU/mL). * Screening electrocardiogram (ECG) without clinically significant abnormalities Key
Exclusion criteria
* Extensive bridging fibrosis or cirrhosis * Received a commercially available HBV OAV treatment(s) within the 3 months prior to screening. * Received prolonged therapy with immunomodulators or biologics within 3 months of screening * Individuals meeting any of the following laboratory parameters at screening: * Alanine aminotransferase \> 5 \* upper limit of normal (ULN) * International normalized ratio \> ULN unless the individual is stable on an anticoagulant regimen * Albumin \< 3.5 g/dL * Direct bilirubin \>1.5x ULN * Platelet Count \< 100,000/µL * Estimated creatinine clearance \< 60 mL/min (using the Cockcroft-Gault method) * Co-infection with human immunodeficiency virus (HIV), hepatitis C virus or hepatitis D virus * Prior history of hepatocellular carcinoma or screening alpha-fetoprotein ≥ 50 ng/mL without imaging * Diagnosis of autoimmune disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease, hemoglobinopathy, retinal disease, or are immunosuppressed. * Chronic liver disease of a non-HBV etiology except for non-alcoholic fatty liver disease. * Received solid organ or bone marrow transplant. * Use of another investigational agent within 90 days of screening, unless allowed by the sponsor. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline at Week 24 | Baseline, Week 24 | — |
| Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | First dose date up to Week 24 plus 30 days | An AE was any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE was any unfavorable and unintended sign, symptom, disease, and/or laboratory or physiological observation that may or may not be related to the investigational medicinal product. A TEAE was defined as any AE with an onset date on or after the first dose date and no later than 30 days after permanent discontinuation of selgantolimod/placebo; or any AE leading to premature discontinuation of study drugs. |
| Percentage of Participants With Treatment-Emergent Laboratory Abnormalities | First dose date up to Week 24 plus 30 days | Treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of the last dose of study drug plus 30 days for selgantolimod/placebo at Week 24. If the relevant baseline laboratory value was missing, any abnormality of at least Grade 1 observed within the time frame specified above was considered treatment emergent. Clinical laboratory results were graded according to Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Serum qHBsAg at Week 8 | Baseline, Week 8 | — |
| Change From Baseline in Serum qHBsAg at Week 12 | Baseline, Week 12 | — |
| Change From Baseline in Serum qHBsAg at Week 24 | Baseline, Week 24 | — |
| Change From Baseline in Serum qHBsAg at Week 48 | Baseline, Week 48 | — |
| Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 8 | Baseline, Week 8 | — |
| Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 12 | Baseline, Week 12 | — |
| Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 48 | Baseline, Week 48 | — |
| Change From Baseline in Serum qHBsAg at Week 4 | Baseline, Week 4 | — |
| Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 4 | Baseline, Week 4 | — |
| Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < Lower Limit of Quantification (LLOQ) at Week 12 | Week 12 | LLOQ was defined as 20 IU/mL. |
| Percentage of Participants With HBV DNA < LLOQ at Week 24 | Week 24 | LLOQ was defined as 20 IU/mL. |
| Percentage of Participants With HBV DNA < LLOQ at Week 48 | Week 48 | LLOQ was defined as 20 IU/mL. |
| Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 12 | Week 12 | HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a postbaseline visit. |
| Percentage of Participants With HBsAg Loss at Week 24 | Week 24 | HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a postbaseline visit. |
| Percentage of Participants With HBsAg Loss at Week 48 | Week 48 | HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a postbaseline visit. |
| Percentage of Participants With HBeAg Loss and Seroconversion at Week 12 | Week 12 | HBeAg loss was defined as qualitative HBeAg changing from positive at baseline to negative at a postbaseline visit. HBeAg seroconversion was defined as Hepatitis B e antibody (HBeAb) loss and anti-HBe change from negative/missing at baseline to positive at a postbaseline visit. |
| Percentage of Participants With HBeAg Loss and Seroconversion at Week 48 | Week 48 | HBeAg loss was defined as qualitative HBeAg changing from positive at baseline to negative at a postbaseline visit. HBeAg seroconversion was defined as HBeAb test changing from negative or missing at baseline to positive at a postbaseline visit. |
| Percentage of Participants With HBeAg Loss and Seroconversion at Week 24 | Week 24 | HBeAg loss was defined as qualitative HBeAg changing from positive at baseline to negative at a postbaseline visit. HBeAg seroconversion was defined as HBeAb loss and anti-HBe change from negative/missing at baseline to positive at a postbaseline visit. |
| Percentage of Participants With Virologic Breakthrough From Baseline up to Week 24 | Baseline up to Week 24 | Virologic breakthrough was defined as confirmed HBV DNA ≥ 69 IU/mL after having been \< 69 IU/mL or confirmed HBV DNA ≥ 1 log10 IU/mL increase from nadir. |
| Percentage of Participants With Virologic Breakthrough From Baseline up to Week 48 | Baseline up to Week 48 | Virologic breakthrough was defined as confirmed HBV DNA ≥ 69 IU/mL after having been \< 69 IU/mL or confirmed HBV DNA ≥ 1 log10 IU/mL increase from nadir. |
| Percentage of Participants With Drug Resistance Mutations | Baseline up to Week 48 | — |
| Pharmacokinetic (PK) Parameter: AUClast of Selgantolimod | Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23 | AUClast is defined as the concentration of drug from time zero to the last observable concentration. |
| PK Parameter: AUC0-24 of Selgantolimod | Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23 | AUC0-24 is defined as the concentration of drug over time from time zero to time 24 hours. |
| PK Parameter: AUCinf of Selgantolimod | Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23 | AUC0-inf is defined as the concentration of drug over time from time zero to infinity. |
| PK Parameter: Cmax of Selgantolimod | Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23 | Cmax is defined as the maximum concentration of drug. |
| PK Parameter: Tmax of Selgantolimod | Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23 | Tmax is defined as the time (observed time point) of Cmax. |
| PK Parameter: CL/F of Selgantolimod | Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23 | CL/F is defined as the apparent oral clearance following administration of the drug. |
| PK Parameter: t1/2 of Selgantolimod | Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23 | t1/2 is defined as the estimate of the terminal elimination half-life of the drug. |
Countries
Canada, South Korea, Taiwan
Participant flow
Recruitment details
Participants were enrolled at study sites in Canada, South Korea, and Taiwan. The first participant was screened on 28 August 2018. The last study visit occurred on 12 April 2021.
Pre-assignment details
96 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Selgantolimod 3 mg + TAF Participants with HBeAg-positive CHB or HBeAg-negative CHB currently not on OAV treatment, received selgantolimod 3 mg (2 x 1.5 mg tablet) orally on the same day once a week (every 7 days) for 24 doses along with the TAF 25 mg orally once daily for 24 weeks. After the 24th dose, selgantolimod was discontinued, and participants continued to receive TAF until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks. | 26 |
| Selgantolimod 1.5 mg + TAF Participants with HBeAg-positive CHB or HBeAg-negative CHB currently not on OAV treatment, received selgantolimod 1.5 mg (1 x 1.5 mg tablet) and placebo (1 tablet) orally on the same day once a week (every 7 days) for 24 doses along with the TAF 25 mg orally once daily for 24 weeks. After the 24th dose, selgantolimod was discontinued, and participants continued to receive TAF until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks. | 28 |
| Placebo + TAF Participants with HBeAg-positive CHB or HBeAg-negative CHB currently not on OAV treatment, received 2 tablets of placebo orally on the same day once a week (every 7 days) for 24 doses along with the TAF 25 mg orally once daily for 24 weeks. After the 24th dose, placebo was discontinued, and participants continued to receive TAF until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks. | 13 |
| Total | 67 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Main Study | Lost to Follow-up | 0 | 0 | 1 |
| Main Study | Withdrew Consent | 0 | 1 | 1 |
| Treatment-free Follow-up (TFFU) Phase | Adverse Event | 1 | 0 | 0 |
| Treatment-free Follow-up (TFFU) Phase | Protocol Violation | 1 | 0 | 0 |
| Treatment-free Follow-up (TFFU) Phase | Withdrew Consent | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Selgantolimod 1.5 mg + TAF | Total | Selgantolimod 3 mg + TAF | Placebo + TAF |
|---|---|---|---|---|
| Age, Continuous | 44 years STANDARD_DEVIATION 12.1 | 45 years STANDARD_DEVIATION 11.3 | 46 years STANDARD_DEVIATION 10.3 | 46 years STANDARD_DEVIATION 12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants | 66 Participants | 26 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| HBsAg | 4.2 log10 IU/mL STANDARD_DEVIATION 0.83 | 4.0 log10 IU/mL STANDARD_DEVIATION 0.82 | 3.8 log10 IU/mL STANDARD_DEVIATION 0.86 | 4.0 log10 IU/mL STANDARD_DEVIATION 0.73 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 28 Participants | 66 Participants | 25 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Canada | 15 participants | 33 participants | 12 participants | 6 participants |
| Region of Enrollment South Korea | 10 participants | 18 participants | 7 participants | 1 participants |
| Region of Enrollment Taiwan | 3 participants | 16 participants | 7 participants | 6 participants |
| Sex: Female, Male Female | 13 Participants | 28 Participants | 11 Participants | 4 Participants |
| Sex: Female, Male Male | 15 Participants | 39 Participants | 15 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 28 | 0 / 13 |
| other Total, other adverse events | 21 / 26 | 15 / 28 | 10 / 13 |
| serious Total, serious adverse events | 1 / 26 | 0 / 28 | 0 / 13 |
Outcome results
Primary
Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline at Week 24
Time frame: Baseline, Week 24
Population: The Full Analysis Set included all randomized participants who took at least 1 dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selgantolimod 3 mg + TAF | Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline at Week 24 | 0 percentage of participants |
| Selgantolimod 1.5 mg + TAF | Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline at Week 24 | 0 percentage of participants |
| Placebo + TAF | Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline at Week 24 | 0 percentage of participants |
Primary
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
An AE was any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE was any unfavorable and unintended sign, symptom, disease, and/or laboratory or physiological observation that may or may not be related to the investigational medicinal product. A TEAE was defined as any AE with an onset date on or after the first dose date and no later than 30 days after permanent discontinuation of selgantolimod/placebo; or any AE leading to premature discontinuation of study drugs.
Time frame: First dose date up to Week 24 plus 30 days
Population: The Safety Analysis Set included all participants who took at least 1 dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selgantolimod 3 mg + TAF | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 84.6 percentage of participants |
| Selgantolimod 1.5 mg + TAF | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 60.7 percentage of participants |
| Placebo + TAF | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 76.9 percentage of participants |
Primary
Percentage of Participants With Treatment-Emergent Laboratory Abnormalities
Treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of the last dose of study drug plus 30 days for selgantolimod/placebo at Week 24. If the relevant baseline laboratory value was missing, any abnormality of at least Grade 1 observed within the time frame specified above was considered treatment emergent. Clinical laboratory results were graded according to Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities.
Time frame: First dose date up to Week 24 plus 30 days
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selgantolimod 3 mg + TAF | Percentage of Participants With Treatment-Emergent Laboratory Abnormalities | 84.6 percentage of participants |
| Selgantolimod 1.5 mg + TAF | Percentage of Participants With Treatment-Emergent Laboratory Abnormalities | 92.9 percentage of participants |
| Placebo + TAF | Percentage of Participants With Treatment-Emergent Laboratory Abnormalities | 92.3 percentage of participants |
Secondary
Change From Baseline in Serum qHBsAg 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 |
|---|---|---|---|
| Selgantolimod 3 mg + TAF | Change From Baseline in Serum qHBsAg at Week 12 | -0.04 log10 IU/mL | Standard Deviation 0.163 |
| Selgantolimod 1.5 mg + TAF | Change From Baseline in Serum qHBsAg at Week 12 | -0.05 log10 IU/mL | Standard Deviation 0.108 |
| Placebo + TAF | Change From Baseline in Serum qHBsAg at Week 12 | 0.01 log10 IU/mL | Standard Deviation 0.099 |
Secondary
Change From Baseline in Serum qHBsAg at Week 24
Time frame: Baseline, Week 24
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Selgantolimod 3 mg + TAF | Change From Baseline in Serum qHBsAg at Week 24 | -0.08 log10 IU/mL | Standard Deviation 0.198 |
| Selgantolimod 1.5 mg + TAF | Change From Baseline in Serum qHBsAg at Week 24 | -0.11 log10 IU/mL | Standard Deviation 0.174 |
| Placebo + TAF | Change From Baseline in Serum qHBsAg at Week 24 | -0.03 log10 IU/mL | Standard Deviation 0.146 |
Secondary
Change From Baseline in Serum qHBsAg 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 |
|---|---|---|---|
| Selgantolimod 3 mg + TAF | Change From Baseline in Serum qHBsAg at Week 4 | -0.04 log10 IU/mL | Standard Deviation 0.155 |
| Selgantolimod 1.5 mg + TAF | Change From Baseline in Serum qHBsAg at Week 4 | -0.01 log10 IU/mL | Standard Deviation 0.081 |
| Placebo + TAF | Change From Baseline in Serum qHBsAg at Week 4 | -0.02 log10 IU/mL | Standard Deviation 0.065 |
Secondary
Change From Baseline in Serum qHBsAg 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 |
|---|---|---|---|
| Selgantolimod 3 mg + TAF | Change From Baseline in Serum qHBsAg at Week 48 | -0.12 log10 IU/mL | Standard Deviation 0.218 |
| Selgantolimod 1.5 mg + TAF | Change From Baseline in Serum qHBsAg at Week 48 | -0.16 log10 IU/mL | Standard Deviation 0.235 |
| Placebo + TAF | Change From Baseline in Serum qHBsAg at Week 48 | -0.12 log10 IU/mL | Standard Deviation 0.145 |
Secondary
Change From Baseline in Serum qHBsAg 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 |
|---|---|---|---|
| Selgantolimod 3 mg + TAF | Change From Baseline in Serum qHBsAg at Week 8 | -0.04 log10 IU/mL | Standard Deviation 0.161 |
| Selgantolimod 1.5 mg + TAF | Change From Baseline in Serum qHBsAg at Week 8 | -0.05 log10 IU/mL | Standard Deviation 0.121 |
| Placebo + TAF | Change From Baseline in Serum qHBsAg at Week 8 | 0.00 log10 IU/mL | Standard Deviation 0.081 |
Secondary
Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 12
Time frame: Baseline, Week 12
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selgantolimod 3 mg + TAF | Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 12 | 0 percentage of participants |
| Selgantolimod 1.5 mg + TAF | Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 12 | 0 percentage of participants |
| Placebo + TAF | Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 12 | 0 percentage of participants |
Secondary
Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 4
Time frame: Baseline, Week 4
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selgantolimod 3 mg + TAF | Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 4 | 0 percentage of participants |
| Selgantolimod 1.5 mg + TAF | Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 4 | 0 percentage of participants |
| Placebo + TAF | Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 4 | 0 percentage of participants |
Secondary
Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 48
Time frame: Baseline, Week 48
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selgantolimod 3 mg + TAF | Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 48 | 0 percentage of participants |
| Selgantolimod 1.5 mg + TAF | Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 48 | 0 percentage of participants |
| Placebo + TAF | Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 48 | 0 percentage of participants |
Secondary
Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 8
Time frame: Baseline, Week 8
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selgantolimod 3 mg + TAF | Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 8 | 0 percentage of participants |
| Selgantolimod 1.5 mg + TAF | Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 8 | 0 percentage of participants |
| Placebo + TAF | Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 8 | 0 percentage of participants |
Secondary
Percentage of Participants With Drug Resistance Mutations
Time frame: Baseline up to Week 48
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selgantolimod 3 mg + TAF | Percentage of Participants With Drug Resistance Mutations | 0 percentage of participants |
| Selgantolimod 1.5 mg + TAF | Percentage of Participants With Drug Resistance Mutations | 0 percentage of participants |
| Placebo + TAF | Percentage of Participants With Drug Resistance Mutations | 0 percentage of participants |
Secondary
Percentage of Participants With HBeAg Loss and Seroconversion at Week 12
HBeAg loss was defined as qualitative HBeAg changing from positive at baseline to negative at a postbaseline visit. HBeAg seroconversion was defined as Hepatitis B e antibody (HBeAb) loss and anti-HBe change from negative/missing at baseline to positive at a postbaseline visit.
Time frame: Week 12
Population: Participants in the Full Analysis Set with available data were analyzed. Analysis was performed only on HBeAg-positive CHB participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Selgantolimod 3 mg + TAF | Percentage of Participants With HBeAg Loss and Seroconversion at Week 12 | HBeAg Loss | 0 percentage of participants |
| Selgantolimod 1.5 mg + TAF | Percentage of Participants With HBeAg Loss and Seroconversion at Week 12 | HBeAg Loss | 0 percentage of participants |
| Placebo + TAF | Percentage of Participants With HBeAg Loss and Seroconversion at Week 12 | HBeAg Loss | 0 percentage of participants |
Secondary
Percentage of Participants With HBeAg Loss and Seroconversion at Week 24
HBeAg loss was defined as qualitative HBeAg changing from positive at baseline to negative at a postbaseline visit. HBeAg seroconversion was defined as HBeAb loss and anti-HBe change from negative/missing at baseline to positive at a postbaseline visit.
Time frame: Week 24
Population: Participants in the Full Analysis Set were analyzed. Analysis was performed only on HBeAg-positive CHB participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Selgantolimod 3 mg + TAF | Percentage of Participants With HBeAg Loss and Seroconversion at Week 24 | HBeAg Loss | 0 percentage of participants |
| Selgantolimod 1.5 mg + TAF | Percentage of Participants With HBeAg Loss and Seroconversion at Week 24 | HBeAg Loss | 0 percentage of participants |
| Placebo + TAF | Percentage of Participants With HBeAg Loss and Seroconversion at Week 24 | HBeAg Loss | 0 percentage of participants |
Secondary
Percentage of Participants With HBeAg Loss and Seroconversion at Week 48
HBeAg loss was defined as qualitative HBeAg changing from positive at baseline to negative at a postbaseline visit. HBeAg seroconversion was defined as HBeAb test changing from negative or missing at baseline to positive at a postbaseline visit.
Time frame: Week 48
Population: Participants in the Full Analysis Set with available data were analyzed. Analysis was performed only on HBeAg-positive CHB participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Selgantolimod 3 mg + TAF | Percentage of Participants With HBeAg Loss and Seroconversion at Week 48 | HBeAg Loss | 0 percentage of participants |
| Selgantolimod 1.5 mg + TAF | Percentage of Participants With HBeAg Loss and Seroconversion at Week 48 | HBeAg Loss | 0 percentage of participants |
| Placebo + TAF | Percentage of Participants With HBeAg Loss and Seroconversion at Week 48 | HBeAg Loss | 0 percentage of participants |
Secondary
Percentage of Participants With HBsAg Loss at Week 24
HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a postbaseline visit.
Time frame: Week 24
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selgantolimod 3 mg + TAF | Percentage of Participants With HBsAg Loss at Week 24 | 0 percentage of participants |
| Selgantolimod 1.5 mg + TAF | Percentage of Participants With HBsAg Loss at Week 24 | 0 percentage of participants |
| Placebo + TAF | Percentage of Participants With HBsAg Loss at Week 24 | 0 percentage of participants |
Secondary
Percentage of Participants With HBsAg Loss at Week 48
HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a postbaseline visit.
Time frame: Week 48
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selgantolimod 3 mg + TAF | Percentage of Participants With HBsAg Loss at Week 48 | 0 percentage of participants |
| Selgantolimod 1.5 mg + TAF | Percentage of Participants With HBsAg Loss at Week 48 | 0 percentage of participants |
| Placebo + TAF | Percentage of Participants With HBsAg Loss at Week 48 | 0 percentage of participants |
Secondary
Percentage of Participants With HBV DNA < LLOQ at Week 24
LLOQ was defined as 20 IU/mL.
Time frame: Week 24
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selgantolimod 3 mg + TAF | Percentage of Participants With HBV DNA < LLOQ at Week 24 | 37.5 percentage of participants |
| Selgantolimod 1.5 mg + TAF | Percentage of Participants With HBV DNA < LLOQ at Week 24 | 32.1 percentage of participants |
| Placebo + TAF | Percentage of Participants With HBV DNA < LLOQ at Week 24 | 33.3 percentage of participants |
Secondary
Percentage of Participants With HBV DNA < LLOQ at Week 48
LLOQ was defined as 20 IU/mL.
Time frame: Week 48
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selgantolimod 3 mg + TAF | Percentage of Participants With HBV DNA < LLOQ at Week 48 | 50.0 percentage of participants |
| Selgantolimod 1.5 mg + TAF | Percentage of Participants With HBV DNA < LLOQ at Week 48 | 44.4 percentage of participants |
| Placebo + TAF | Percentage of Participants With HBV DNA < LLOQ at Week 48 | 45.5 percentage of participants |
Secondary
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 12
HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a postbaseline visit.
Time frame: Week 12
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selgantolimod 3 mg + TAF | Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 12 | 0 percentage of participants |
| Selgantolimod 1.5 mg + TAF | Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 12 | 0 percentage of participants |
| Placebo + TAF | Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 12 | 0 percentage of participants |
Secondary
Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < Lower Limit of Quantification (LLOQ) at Week 12
LLOQ was defined as 20 IU/mL.
Time frame: Week 12
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selgantolimod 3 mg + TAF | Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < Lower Limit of Quantification (LLOQ) at Week 12 | 20.8 percentage of participants |
| Selgantolimod 1.5 mg + TAF | Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < Lower Limit of Quantification (LLOQ) at Week 12 | 28.6 percentage of participants |
| Placebo + TAF | Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < Lower Limit of Quantification (LLOQ) at Week 12 | 25.0 percentage of participants |
Secondary
Percentage of Participants With Virologic Breakthrough From Baseline up to Week 24
Virologic breakthrough was defined as confirmed HBV DNA ≥ 69 IU/mL after having been \< 69 IU/mL or confirmed HBV DNA ≥ 1 log10 IU/mL increase from nadir.
Time frame: Baseline up to Week 24
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selgantolimod 3 mg + TAF | Percentage of Participants With Virologic Breakthrough From Baseline up to Week 24 | 3.8 percentage of participants |
| Selgantolimod 1.5 mg + TAF | Percentage of Participants With Virologic Breakthrough From Baseline up to Week 24 | 7.1 percentage of participants |
| Placebo + TAF | Percentage of Participants With Virologic Breakthrough From Baseline up to Week 24 | 15.4 percentage of participants |
Secondary
Percentage of Participants With Virologic Breakthrough From Baseline up to Week 48
Virologic breakthrough was defined as confirmed HBV DNA ≥ 69 IU/mL after having been \< 69 IU/mL or confirmed HBV DNA ≥ 1 log10 IU/mL increase from nadir.
Time frame: Baseline up to Week 48
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selgantolimod 3 mg + TAF | Percentage of Participants With Virologic Breakthrough From Baseline up to Week 48 | 3.8 percentage of participants |
| Selgantolimod 1.5 mg + TAF | Percentage of Participants With Virologic Breakthrough From Baseline up to Week 48 | 10.7 percentage of participants |
| Placebo + TAF | Percentage of Participants With Virologic Breakthrough From Baseline up to Week 48 | 15.4 percentage of participants |
Secondary
Pharmacokinetic (PK) Parameter: AUClast of Selgantolimod
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Time frame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23
Population: Participants in the PK Substudy Analysis Set (all randomized participants who took at least 1 dose of the study drug, participated in the optional intensive PK substudy, and had at least 1 nonmissing postdose concentration) with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Selgantolimod 3 mg + TAF | Pharmacokinetic (PK) Parameter: AUClast of Selgantolimod | Day 1 | 1163.0 hr*pg/mL | Standard Deviation 833.27 |
| Selgantolimod 3 mg + TAF | Pharmacokinetic (PK) Parameter: AUClast of Selgantolimod | Week 23 | 1441.8 hr*pg/mL | Standard Deviation 1601.19 |
| Selgantolimod 1.5 mg + TAF | Pharmacokinetic (PK) Parameter: AUClast of Selgantolimod | Day 1 | 548.0 hr*pg/mL | Standard Deviation 393 |
| Selgantolimod 1.5 mg + TAF | Pharmacokinetic (PK) Parameter: AUClast of Selgantolimod | Week 23 | 491.2 hr*pg/mL | Standard Deviation 489.29 |
Secondary
PK Parameter: AUC0-24 of Selgantolimod
AUC0-24 is defined as the concentration of drug over time from time zero to time 24 hours.
Time frame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Selgantolimod 3 mg + TAF | PK Parameter: AUC0-24 of Selgantolimod | Day 1 | 1162.2 hr*pg/mL | Standard Deviation 832.29 |
| Selgantolimod 3 mg + TAF | PK Parameter: AUC0-24 of Selgantolimod | Week 23 | 1440.5 hr*pg/mL | Standard Deviation 1598.05 |
| Selgantolimod 1.5 mg + TAF | PK Parameter: AUC0-24 of Selgantolimod | Day 1 | 547.7 hr*pg/mL | Standard Deviation 392.77 |
| Selgantolimod 1.5 mg + TAF | PK Parameter: AUC0-24 of Selgantolimod | Week 23 | 494.4 hr*pg/mL | Standard Deviation 485.56 |
Secondary
PK Parameter: AUCinf of Selgantolimod
AUC0-inf is defined as the concentration of drug over time from time zero to infinity.
Time frame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Selgantolimod 3 mg + TAF | PK Parameter: AUCinf of Selgantolimod | Day 1 | 1184.2 hr*pg/mL | Standard Deviation 843.53 |
| Selgantolimod 3 mg + TAF | PK Parameter: AUCinf of Selgantolimod | Week 23 | 1462.8 hr*pg/mL | Standard Deviation 1616.7 |
| Selgantolimod 1.5 mg + TAF | PK Parameter: AUCinf of Selgantolimod | Day 1 | 556.4 hr*pg/mL | Standard Deviation 394.38 |
| Selgantolimod 1.5 mg + TAF | PK Parameter: AUCinf of Selgantolimod | Week 23 | 503.2 hr*pg/mL | Standard Deviation 492.66 |
Secondary
PK Parameter: CL/F of Selgantolimod
CL/F is defined as the apparent oral clearance following administration of the drug.
Time frame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Selgantolimod 3 mg + TAF | PK Parameter: CL/F of Selgantolimod | Day 1 | 4094330.4 mL/hr | Standard Deviation 3034917.79 |
| Selgantolimod 3 mg + TAF | PK Parameter: CL/F of Selgantolimod | Week 23 | 4550308.6 mL/hr | Standard Deviation 3858788.24 |
| Selgantolimod 1.5 mg + TAF | PK Parameter: CL/F of Selgantolimod | Day 1 | 4603039.8 mL/hr | Standard Deviation 3733427.89 |
| Selgantolimod 1.5 mg + TAF | PK Parameter: CL/F of Selgantolimod | Week 23 | 6223868.1 mL/hr | Standard Deviation 5265428.49 |
Secondary
PK Parameter: Cmax of Selgantolimod
Cmax is defined as the maximum concentration of drug.
Time frame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Selgantolimod 3 mg + TAF | PK Parameter: Cmax of Selgantolimod | Day 1 | 373.3 pg/mL | Standard Deviation 208.63 |
| Selgantolimod 3 mg + TAF | PK Parameter: Cmax of Selgantolimod | Week 23 | 591.0 pg/mL | Standard Deviation 565.11 |
| Selgantolimod 1.5 mg + TAF | PK Parameter: Cmax of Selgantolimod | Day 1 | 307.7 pg/mL | Standard Deviation 311.12 |
| Selgantolimod 1.5 mg + TAF | PK Parameter: Cmax of Selgantolimod | Week 23 | 268.2 pg/mL | Standard Deviation 254.16 |
Secondary
PK Parameter: t1/2 of Selgantolimod
t1/2 is defined as the estimate of the terminal elimination half-life of the drug.
Time frame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Selgantolimod 3 mg + TAF | PK Parameter: t1/2 of Selgantolimod | Week 23 | 4.78 hours |
| Selgantolimod 3 mg + TAF | PK Parameter: t1/2 of Selgantolimod | Day 1 | 4.55 hours |
| Selgantolimod 1.5 mg + TAF | PK Parameter: t1/2 of Selgantolimod | Day 1 | 5.13 hours |
| Selgantolimod 1.5 mg + TAF | PK Parameter: t1/2 of Selgantolimod | Week 23 | 5.03 hours |
Secondary
PK Parameter: Tmax of Selgantolimod
Tmax is defined as the time (observed time point) of Cmax.
Time frame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Selgantolimod 3 mg + TAF | PK Parameter: Tmax of Selgantolimod | Day 1 | 0.98 hours |
| Selgantolimod 3 mg + TAF | PK Parameter: Tmax of Selgantolimod | Week 23 | 0.55 hours |
| Selgantolimod 1.5 mg + TAF | PK Parameter: Tmax of Selgantolimod | Day 1 | 0.53 hours |
| Selgantolimod 1.5 mg + TAF | PK Parameter: Tmax of Selgantolimod | Week 23 | 0.50 hours |