Chronic Hepatitis B
Conditions
Brief summary
The primary objective of this study is to evaluate the safety and tolerability and virologic response of tenofovir alafenamide (TAF) in virologically suppressed chronic hepatitis B participants with renal and/or hepatic impairment.
Interventions
DRUGTAF
Tablet administered orally once daily
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: All Participants (Parts A and B): * Adult male or non-pregnant female individuals * Documented evidence of chronic HBV infection * Alanine aminotransferase (ALT) ≤ 10 × upper limit of normal (ULN) Part A Only (renal impairment): * Maintained on TDF and/or other OAV treatment(s) for CHB for at least 48 weeks and with viral suppression (HBV deoxyribonucleic acid \[DNA\] \< lower limit of quantitation \[LLOQ\]) for ≥ 6 months prior to screening * All individuals must have HBV DNA \< 20 International units per milliliter (IU/mL) at screening by central laboratory * Both Hepatitis B e-Antigen (HBeAg) positive and negative individuals are eligible to participate * Moderate renal impairment (30 milliliters per minute \[mL/min\] ≤ estimated glomerular filtration rate by the cockcroft-gault formula \[eGFRcg\] ≤ 59 mL/min), severe renal impairment (15 mL/min ≤ eGFRcg \< 30 mL/min) or end stage renal disease (ESRD) (eGFR \< 15 mL/min) maintained on hemodialysis (HD) * Stable renal function (for participants with moderate or severe impairment): serum creatinine measured at least once within three months prior to screening. The measurement difference between the value measured within three months prior to screening versus the screening value must be ≤ 25% of the screening value Part B Only (hepatic impairment): * Maintained on TDF and/or other OAV(s) for CHB for at least 48 weeks and with viral suppression (HBV DNA \< LLOQ) for ≥ 6 months prior to screening * All individuals must have HBV DNA \< 20 IU/mL at screening by central laboratory * Both HBeAg positive and negative individuals are eligible to participate * Child-pugh-turcotte (CPT) score of 7-12 (inclusive) OR a past history of CPT score ≥ 7 and any CPT score ≤ 12 at screening * eGFRCG ≥ 30 mL/min using the Cockcroft-Gault equation Key
Exclusion criteria
All Individuals (Parts A & B): * Women who are breastfeeding or who believe they may wish to become pregnant during the course of the study * Males and females of reproductive potential who are unwilling to use an effective, protocol-specified method(s) of contraception during the study * Co-infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or hepatitis D virus (HDV) * Prior Interferon (IFN) use within 6 months of screening * Evidence of hepatocellular carcinoma * Received solid organ or bone marrow transplant * Significant cardiovascular, pulmonary, or neurological disease * Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc.). Individuals under evaluation for possible malignancy are not eligible * Currently receiving therapy with immunomodulators (e.g. corticosteroids), nephrotoxic agents, or agents capable of modifying renal excretion * Known hypersensitivity to study drugs, metabolites, or formulation excipients * Current alcohol or substance abuse judged by the investigator to potentially interfere with individual's compliance * Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the individual unsuitable for the study or unable to comply with dosing requirements. Part A Only (Renal Impairment): * Current or historical evidence of clinical hepatic decompensation (e.g., ascites, encephalopathy or variceal hemorrhage) * Abnormal hematological and biochemical parameters, including: * Hemoglobin \< 9 grams per deciliter (g/dL) * Absolute neutrophil count \< 750/cubic millimeter (mm\^3) * Platelets ≤ 50,000/mm\^3 * Aspartate aminotransferase (AST) \> 10 × ULN * Albumin \< 3.0 g/dL * Total bilirubin \> 2.5 × ULN * International normalized ratio of prothrombin time (INR) \> 1.5 × ULN (unless stable on anticoagulant regimen) * Individuals with ESRD (i.e. eGFRcg \< 15 mL/min) not on HD, or those on other forms of renal replacement therapy (i.e. peritoneal dialysis) Part B Only (Hepatic Impairment): * Active variceal bleeding within 6 months or prior placement of a portosystemic shunt (such as transjugular intrahepatic portosystemic shunt \[TIPS\]) * History of hepatorenal syndrome, hepatopulmonary syndrome, Grade 3 or Grade 4 hepatic encephalopathy, or spontaneous bacterial peritonitis within 6 months of screening * Grade 2 hepatic encephalopathy at screening * Model for end-stage liver disease (MELD) score ≥ 30 * Abnormal hematological and biochemical parameters, including * Absolute neutrophil count \< 750/mm\^3 * Platelets \< 30,000/mm\^3 * Hemoglobin \< 8.0 g/dL Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Virologic Response (Plasma Hepatitis B Virus [HBV] Deoxyribonucleic Acid [DNA] < 20 IU/mL) at Week 24 | Week 24 | The percentage of participants with HBV DNA \< 20 IU/mL at Week 24 was determined by the Missing = Failure (M = F) approach. |
| Percentage of Participants Who Experienced Graded Treatment-Emergent Adverse Events (AEs) at Week 24 | Week 24 | Treatment-emergent AEs were defined as: * Any AEs with an onset date on or after the study drug start date and no later than the study drug stop date + 3 days after permanent discontinuation of study drug; * Any AEs with onset date on or after the study drug start date for those who have not permanently discontinued study drug; * Any AEs leading to premature discontinuation of study drug. The most severe graded AE from all tests was counted for each participant. |
| Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 24 | Week 24 | Graded treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any postbaseline visit, up to and including the date of last dose of study drug + 3 days for participants who permanently discontinued study drug or the last available date in the database snapshot for participants who were on treatment at the time of the analysis. The most severe graded abnormality from all tests was counted for each participant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 96 | Week 96 | Graded treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any post-baseline visit, up to and including the date of last dose of study drug + 3 days for participants who permanently discontinued study drug or the last available date in the database snapshot for participants who were on treatment at the time of the analysis. The most severe graded abnormality from all tests was counted for each participant. |
| Change From Baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFRcg) in Participants With Moderate or Severe Renal Impairment and Hepatically Impaired Participants at Week 24 | Baseline, Week 24 | GFR is a measure of the rate at which blood is filtered by the kidney. Cockcroft-Gault is an equation (calculation) used to estimate GFR based on serum creatinine, weight, and gender. eGFRcg = (140 - age in years) x (body weight in kg) x (0.85 if female) divided by 72 x serum creatinine in mg/dL. Moderate renal impairment= 30 mL/min ≤ eGFRCG ≤ 59 mL/min Severe renal impairment= 15 mL/min ≤ eGFRCG \< 30 mL/min Change from baseline was calculated as the value at Week 24 minus the value at Baseline. |
| Change From Baseline in eGFRcg in Participants With Moderate or Severe Renal Impairment and Hepatically Impaired Participants at Week 48 | Baseline, Week 48 | GFR is a measure of the rate at which blood is filtered by the kidney. Cockcroft-Gault is an equation (calculation) used to estimate GFR based on serum creatinine, weight, and gender. eGFRcg = (140 - age in years) x (body weight in kg) x (0.85 if female) divided by 72 x serum creatinine in mg/dL. Moderate renal impairment= 30 mL/min ≤ eGFRCG ≤ 59 mL/min Severe renal impairment= 15 mL/min ≤ eGFRCG \< 30 mL/min Change from baseline was calculated as the value at Week 48 minus the value at Baseline. |
| Change From Baseline in eGFRcg in Participants With Moderate or Severe Renal Impairment and Hepatically Impaired Participants at Week 96 | Baseline, Week 96 | GFR is a measure of the rate at which blood is filtered by the kidney. Cockcroft-Gault is an equation (calculation) used to estimate GFR based on serum creatinine, weight, and gender. eGFRcg = (140 - age in years) x (body weight in kg) x (0.85 if female) divided by 72 x serum creatinine in mg/dL. Moderate renal impairment= 30 mL/min ≤ eGFRCG ≤ 59 mL/min Severe renal impairment= 15 mL/min ≤ eGFRCG \< 30 mL/min Change from baseline was calculated as the value at Week 96 minus the value at Baseline. |
| Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 24 | Baseline, Week 24 | Percent change = Change from baseline at a postbaseline visit/baseline \* 100%. |
| Percent Change From Baseline in Hip BMD at Week 48 | Baseline, Week 48 | Percent change = Change from baseline at a postbaseline visit/baseline \* 100%. |
| Percent Change From Baseline in Hip BMD at Week 96 | Baseline, Week 96 | Percent change = Change from baseline at a postbaseline visit/baseline \* 100%. |
| Percent Change From Baseline in Spine BMD at Week 24 | Baseline, Week 24 | Percent change = Change from baseline at a postbaseline visit/baseline \* 100%. |
| Percent Change From Baseline in Spine BMD at Week 48 | Baseline, Week 48 | Percent change = Change from baseline at a postbaseline visit/baseline \* 100%. |
| Percent Change From Baseline in Spine BMD at Week 96 | Baseline, Week 96 | Percent change = Change from baseline at a postbaseline visit/baseline \* 100%. |
| Percentage of Participants Achieving Virologic Response (Plasma HBV DNA < 20 IU/mL) at Week 48 | Weeks 48 | The percentage of participants with HBV DNA \< 20 IU/mL at Week 48 was determined by the Missing = Failure (M = F) approach. |
| Percentage of Participants Achieving Virologic Response (Plasma HBV DNA < 20 IU/mL) at Week 96 | Weeks 96 | The percentage of participants with HBV DNA \< 20 IU/mL at Week 48 was determined by the Missing = Failure (M = F) approach. |
| Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (≥ Lower Limit of Detection [LLOD]) at Week 24 | Week 24 | The percentage of participants with HBV DNA \< 20 IU/mL and target detected (≥ LLOD; i.e. 10 IU/mL) at Week 24 was determined by the M = F approach. |
| Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (≥ LLOD) at Week 48 | Week 48 | The percentage of participants with HBV DNA \< 20 IU/mL and target detected (≥ LLOD; i.e. 10 IU/mL) at Week 48 was determined by the M = F approach. |
| Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (≥ LLOD) at Week 96 | Week 96 | The percentage of participants with HBV DNA \< 20 IU/mL and target detected (≥ LLOD; i.e. 10 IU/mL) at Week 96 was determined by the M = F approach. |
| Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 24 | Week 24 | The percentage of participants with HBV DNA \< 20 IU/mL and target not detected (\< LLOD; i.e. 10 IU/mL) at Week 24 was determined by the M = F approach. |
| Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 96 | Week 96 | HBeAg loss was defined as HBeAg changing from positive at baseline to negative at a postbaseline. The M = F approach was used for this analysis. |
| Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 48 | Weeks 48 | The percentage of participants with HBV DNA \< 20 IU/mL and target not detected (\< LLOD; i.e. 10 IU/mL) at Week 48 was determined by the M = F approach. |
| Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 96 | Weeks 96 | The percentage of participants with HBV DNA \< 20 IU/mL and target not detected (\< LLOD; i.e. 10 IU/mL) at Week 96 was determined by the M = F approach. |
| Percentage of Participants With Serological Response: Loss of Hepatitis B s-Antigen (HBsAg) at Week 24 | Week 24 | HBsAg loss was defined as HBsAg changing from positive at baseline to negative at a postbaseline. The M = F approach was used for this analysis. |
| Percentage of Participants With Serological Response: Loss of HBsAg at Week 48 | Week 48 | HBsAg loss was defined as HBsAg changing from positive at baseline to negative at a postbaseline. The M = F approach was used for this analysis. |
| Percentage of Participants With Serological Response: Loss of HBsAg at Week 96 | Week 96 | HBsAg loss was defined as HBsAg changing from positive at baseline to negative at a postbaseline. The M = F approach was used for this analysis. |
| Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 24 | Week 24 | HBsAg seroconversion was defined as HBsAg loss and HBsAb test changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis. |
| Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 48 | Week 48 | HBsAg seroconversion was defined as HBsAg loss and HBsAb test changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis. |
| Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 96 | Week 96 | HBsAg seroconversion was defined as HBsAg loss and HBsAb test changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis. |
| Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 24 | Week 24 | HBeAg loss was defined as HBeAg changing from positive at baseline to negative at a postbaseline. The M = F approach was used for this analysis. |
| Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 48 | Week 48 | HBeAg loss was defined as HBeAg changing from positive at baseline to negative at a postbaseline. The M = F approach was used for this analysis. |
| Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 24 | Week 24 | HBeAg seroconversion was defined as HBeAg loss and HBeAb test changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis. |
| Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 48 | Week 48 | HBeAg seroconversion was defined as HBeAg loss and HBeAb test changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis. |
| Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 96 | Week 96 | HBeAg seroconversion was defined as HBeAg loss and HBeAb test changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis. |
| Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Week 24 by Central Laboratory and the American Association for the Study of Liver Diseases (AASLD) Criteria | Week 24 | Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to \< 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to \< 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. The M = F approach was used for this analysis. |
| Percentage of Participants With Normal ALT at Week 48 by Central Laboratory and the AASLD Criteria | Week 48 | Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to \< 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to \< 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. The M = F approach was used for this analysis. |
| Percentage of Participants With Normal ALT at Week 96 by Central Laboratory and the AASLD Criteria | Week 96 | Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to \< 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to \< 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. The M = F approach was used for this analysis. |
| Percentage of Participants With Normalized ALT at Week 24 by Central Laboratory and the AASLD Criteria | Week 24 | ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit. Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to \< 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to \< 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. The M = F approach was used for this analysis. |
| Percentage of Participants With Normalized ALT at Week 48 by Central Laboratory and the AASLD Criteria | Week 48 | ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit. Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to \< 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to \< 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. The M = F approach was used for this analysis. |
| Percentage of Participants With Normalized ALT at Week 96 by Central Laboratory and the AASLD Criteria | Week 96 | ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit. Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to \< 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to \< 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. The M = F approach was used for this analysis. |
| Change From Baseline in FibroTest® Score at Week 24 | Baseline, Week 24 | The FibroTest® score is used to assess liver fibrosis. Scores range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis. Change from baseline was calculated as the value at Week 24 minus the value at Baseline. |
| Change From Baseline in FibroTest® Score at Week 48 | Baseline, Week 48 | The FibroTest® score is used to assess liver fibrosis. Scores range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis. Change from baseline was calculated as the value at Week 48 minus the value at Baseline. |
| Change From Baseline in FibroTest® Score at Week 96 | Week 96 | The FibroTest® score is used to assess liver fibrosis. Scores range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis. Change from baseline was calculated as the value at Week 96 minus the value at Baseline. |
| Change From Baseline in Child-Pugh-Turcotte (CPT) Score in Hepatically Impaired Participants at Week 24 | Baseline, Week 24 | CPT scores grade the severity of cirrhosis and are used to determine the need for liver transplantation. Scores can range from 5 to 15, with higher scores indicating a greater severity of disease. |
| Change From Baseline in CPT Score in Hepatically Impaired Participants at Week 48 | Baseline, Week 48 | CPT scores grade the severity of cirrhosis and are used to determine the need for liver transplantation. Scores can range from 5 to 15, with higher scores indicating a greater severity of disease. |
| Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 48 | Week 48 | Treatment-emergent AEs were defined as: Any AEs with an onset date on or after the study drug start date and no later than the study drug stop date + 3 days after permanent discontinuation of study drug; Any AEs with onset date on or after the study drug start date for those who have not permanently discontinued study drug; Any AEs leading to premature discontinuation of study drug. The most severe graded AE from all tests was counted for each participant. |
| Change From Baseline in Model for End-Stage Liver Disease (MELD) Score in Hepatically Impaired Participants at Week 24 | Baseline, Week 24 | MELD scores are used to assess prognosis and suitability for liver transplantation. Scores can range from 6 to 40, with higher scores indicating greater disease severity. |
| Change From Baseline in MELD Score in Hepatically Impaired Participants at Week 48 | Baseline, Week 48 | MELD scores are used to assess prognosis and suitability for liver transplantation. Scores can range from 6 to 40, with higher scores indicating greater disease severity. |
| Change From Baseline in MELD Score in Hepatically Impaired Participants at Week 96 | Baseline, Week 96 | MELD scores are used to assess prognosis and suitability for liver transplantation. Scores can range from 6 to 40, with higher scores indicating greater disease severity. |
| Change From Baseline in CPT Score in Hepatically Impaired Participants at Week 96 | Baseline, Week 96 | CPT scores grade the severity of cirrhosis and are used to determine the need for liver transplantation. Scores can range from 5 to 15, with higher scores indicating a greater severity of disease. |
| Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 96 | Week 96 | Treatment-emergent AEs were defined as: Any AEs with an onset date on or after the study drug start date and no later than the study drug stop date + 3 days after permanent discontinuation of study drug; Any AEs with onset date on or after the study drug start date for those who have not permanently discontinued study drug; Any AEs leading to premature discontinuation of study drug. The most severe graded AE from all tests was counted for each participant. |
| Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 48 | Week 48 | Graded treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any postbaseline visit, up to and including the date of last dose of study drug + 3 days for participants who permanently discontinued study drug or the last available date in the database snapshot for participants who were on treatment at the time of the analysis. The most severe graded abnormality from all tests was counted for each participant. |
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 Pacific, North America, New Zealand and Europe. The first participant was screened on 29 June 2017. The last study visit occurred on 04 September 2020.
Pre-assignment details
147 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment Participants with CHB and moderate or severe renal impairment who were virologically suppressed and taking TDF, a TDF-containing anti-HBV regimen, or other OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. | 78 |
| Part A (Renal Impairment): End Stage Renal Disease Participants with CHB and end stage renal disease who were virologically suppressed and taking TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. | 15 |
| Part B: Hepatic Impairment Participants with CHB and moderate or severe hepatic impairment who were virologically suppressed and taking TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. | 31 |
| Total | 124 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 1 |
| Overall Study | Death | 2 | 1 | 2 |
| Overall Study | Investigator's discretion | 2 | 0 | 1 |
| Overall Study | Withdrew Consent | 5 | 0 | 2 |
Baseline characteristics
| Characteristic | Part A (Renal Impairment): End Stage Renal Disease | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Total | Part B: Hepatic Impairment |
|---|---|---|---|---|
| Age, Continuous | 54 years STANDARD_DEVIATION 12.8 | 66 years STANDARD_DEVIATION 10.1 | 61 years STANDARD_DEVIATION 11.8 | 55 years STANDARD_DEVIATION 10.8 |
| Alanine Aminotransferase (ALT) | 14 Units/Liter (U/L) STANDARD_DEVIATION 5.2 | 20 Units/Liter (U/L) STANDARD_DEVIATION 9.6 | 21 Units/Liter (U/L) STANDARD_DEVIATION 10.8 | 28 Units/Liter (U/L) STANDARD_DEVIATION 12.4 |
| ALT Level Based on 2018 American Association for the Study of Liver Diseases (AASLD) Normal Range > 5xULN | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| ALT Level Based on 2018 American Association for the Study of Liver Diseases (AASLD) Normal Range ≤ ULN | 15 Participants | 73 Participants | 109 Participants | 21 Participants |
| ALT Level Based on 2018 American Association for the Study of Liver Diseases (AASLD) Normal Range > ULN - 5xULN | 0 Participants | 5 Participants | 15 Participants | 10 Participants |
| ALT Level Based on Central Lab Normal Range > 5xULN | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| ALT Level Based on Central Lab Normal Range ≤ ULN | 15 Participants | 75 Participants | 117 Participants | 27 Participants |
| ALT Level Based on Central Lab Normal Range > ULN - 5xULN | 0 Participants | 3 Participants | 7 Participants | 4 Participants |
| Child-Pugh-Turcotte (CPT) Score | — | — | 6 units on a scale STANDARD_DEVIATION 1.7 | 6 units on a scale STANDARD_DEVIATION 1.7 |
| Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFRcg) | 7.8 milliliter/minute (mL/min) STANDARD_DEVIATION 2.63 | 45.5 milliliter/minute (mL/min) STANDARD_DEVIATION 10.89 | 54.3 milliliter/minute (mL/min) STANDARD_DEVIATION 34.16 | 98.8 milliliter/minute (mL/min) STANDARD_DEVIATION 33.94 |
| FibroTest® Score | 0.37 units on a scale STANDARD_DEVIATION 0.199 | 0.53 units on a scale STANDARD_DEVIATION 0.199 | 0.57 units on a scale STANDARD_DEVIATION 0.231 | 0.75 units on a scale STANDARD_DEVIATION 0.206 |
| Hepatitis B e Antigen/Antibody (HBeAg/HBeAb) Status Negative/Negative | 1 Participants | 15 Participants | 26 Participants | 10 Participants |
| Hepatitis B e Antigen/Antibody (HBeAg/HBeAb) Status Negative/Positive | 11 Participants | 50 Participants | 79 Participants | 18 Participants |
| Hepatitis B e Antigen/Antibody (HBeAg/HBeAb) Status Positive/Negative | 3 Participants | 13 Participants | 19 Participants | 3 Participants |
| Hepatitis B e Antigen/Antibody (HBeAg/HBeAb) Status Positive/Positive | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Categories < 20 IU/mL | 14 Participants | 77 Participants | 122 Participants | 31 Participants |
| Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Categories ≥ 20 IU/mL - < 69 IU/mL | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Categories ≥ 69 IU/mL | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Hepatitis s-Antigen (HBsAg) (log10 IU/mL) | 2.72 log10 IU/mL STANDARD_DEVIATION 1.405 | 2.51 log10 IU/mL STANDARD_DEVIATION 0.782 | 2.38 log10 IU/mL STANDARD_DEVIATION 1.012 | 1.90 log10 IU/mL STANDARD_DEVIATION 1.169 |
| Hip Bone Mineral Density (BMD) Status Normal (T-score ≥ -1.0) | 3 Participants | 34 Participants | 55 Participants | 18 Participants |
| Hip Bone Mineral Density (BMD) Status Osteopenia (-2.5 ≤ T-score < -1.0) | 5 Participants | 36 Participants | 53 Participants | 12 Participants |
| Hip Bone Mineral Density (BMD) Status Osteoporosis (T-score < -2.5) | 7 Participants | 7 Participants | 15 Participants | 1 Participants |
| Model for End-Stage Liver Disease (MELD) Score | — | — | 10.7 units on a scale STANDARD_DEVIATION 3.4 | 10.7 units on a scale STANDARD_DEVIATION 3.4 |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 15 Participants | 78 Participants | 123 Participants | 30 Participants |
| Race/Ethnicity, Customized Race Asian | 13 Participants | 59 Participants | 97 Participants | 25 Participants |
| Race/Ethnicity, Customized Race Black or African American | 0 Participants | 3 Participants | 4 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Pacific Islander | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Other | 0 Participants | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 0 Participants | 15 Participants | 19 Participants | 4 Participants |
| Region of Enrollment Canada | 0 Participants | 22 Participants | 25 Participants | 3 Participants |
| Region of Enrollment Hong Kong | 1 Participants | 14 Participants | 17 Participants | 2 Participants |
| Region of Enrollment Italy | 0 Participants | 13 Participants | 15 Participants | 2 Participants |
| Region of Enrollment New Zealand | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Region of Enrollment South Korea | 3 Participants | 12 Participants | 20 Participants | 5 Participants |
| Region of Enrollment Taiwan | 9 Participants | 13 Participants | 33 Participants | 11 Participants |
| Region of Enrollment United Kingdom | 0 Participants | 1 Participants | 2 Participants | 1 Participants |
| Region of Enrollment United States | 0 Participants | 3 Participants | 10 Participants | 7 Participants |
| Sex: Female, Male Female | 3 Participants | 21 Participants | 34 Participants | 10 Participants |
| Sex: Female, Male Male | 12 Participants | 57 Participants | 90 Participants | 21 Participants |
| Spine BMD Status Normal (T-score ≥ -1.0) | 5 Participants | 37 Participants | 58 Participants | 16 Participants |
| Spine BMD Status Osteopenia (-2.5 ≤ T-score < -1.0) | 7 Participants | 22 Participants | 38 Participants | 9 Participants |
| Spine BMD Status Osteoporosis (T-score < -2.5) | 3 Participants | 19 Participants | 28 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 78 | 1 / 15 | 2 / 31 |
| other Total, other adverse events | 34 / 78 | 15 / 15 | 23 / 31 |
| serious Total, serious adverse events | 12 / 78 | 8 / 15 | 10 / 31 |
Outcome results
Primary
Percentage of Participants Achieving Virologic Response (Plasma Hepatitis B Virus [HBV] Deoxyribonucleic Acid [DNA] < 20 IU/mL) at Week 24
The percentage of participants with HBV DNA \< 20 IU/mL at Week 24 was determined by the Missing = Failure (M = F) approach.
Time frame: Week 24
Population: The Full Analysis Set included all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants Achieving Virologic Response (Plasma Hepatitis B Virus [HBV] Deoxyribonucleic Acid [DNA] < 20 IU/mL) at Week 24 | 97.4 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants Achieving Virologic Response (Plasma Hepatitis B Virus [HBV] Deoxyribonucleic Acid [DNA] < 20 IU/mL) at Week 24 | 100.0 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants Achieving Virologic Response (Plasma Hepatitis B Virus [HBV] Deoxyribonucleic Acid [DNA] < 20 IU/mL) at Week 24 | 100.0 percentage of participants |
Primary
Percentage of Participants Who Experienced Graded Treatment-Emergent Adverse Events (AEs) at Week 24
Treatment-emergent AEs were defined as: * Any AEs with an onset date on or after the study drug start date and no later than the study drug stop date + 3 days after permanent discontinuation of study drug; * Any AEs with onset date on or after the study drug start date for those who have not permanently discontinued study drug; * Any AEs leading to premature discontinuation of study drug. The most severe graded AE from all tests was counted for each participant.
Time frame: Week 24
Population: The Safety Analysis Set included all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants Who Experienced Graded Treatment-Emergent Adverse Events (AEs) at Week 24 | Any Treatment-emergent AEs | 53.8 percentage of participants |
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants Who Experienced Graded Treatment-Emergent Adverse Events (AEs) at Week 24 | Grade 3 and Above Treatment-emergent AEs | 6.4 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants Who Experienced Graded Treatment-Emergent Adverse Events (AEs) at Week 24 | Any Treatment-emergent AEs | 73.3 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants Who Experienced Graded Treatment-Emergent Adverse Events (AEs) at Week 24 | Grade 3 and Above Treatment-emergent AEs | 13.3 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants Who Experienced Graded Treatment-Emergent Adverse Events (AEs) at Week 24 | Any Treatment-emergent AEs | 54.8 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants Who Experienced Graded Treatment-Emergent Adverse Events (AEs) at Week 24 | Grade 3 and Above Treatment-emergent AEs | 6.5 percentage of participants |
Primary
Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 24
Graded treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any postbaseline visit, up to and including the date of last dose of study drug + 3 days for participants who permanently discontinued study drug or the last available date in the database snapshot for participants who were on treatment at the time of the analysis. The most severe graded abnormality from all tests was counted for each participant.
Time frame: Week 24
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 24 | Any Graded Laboratory Abnormality | 96.2 percentage of participants |
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 24 | Grade 3 and Above Laboratory Abnormality | 11.5 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 24 | Any Graded Laboratory Abnormality | 100.0 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 24 | Grade 3 and Above Laboratory Abnormality | 46.7 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 24 | Any Graded Laboratory Abnormality | 90.3 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 24 | Grade 3 and Above Laboratory Abnormality | 48.4 percentage of participants |
Secondary
Change From Baseline in Child-Pugh-Turcotte (CPT) Score in Hepatically Impaired Participants at Week 24
CPT scores grade the severity of cirrhosis and are used to determine the need for liver transplantation. Scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Time frame: Baseline, Week 24
Population: Participants in the Full Analysis Set only from Part B (Hepatic Impairment) were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Change From Baseline in Child-Pugh-Turcotte (CPT) Score in Hepatically Impaired Participants at Week 24 | 0 units on a scale | Standard Deviation 1.1 |
Secondary
Change From Baseline in CPT Score in Hepatically Impaired Participants at Week 48
CPT scores grade the severity of cirrhosis and are used to determine the need for liver transplantation. Scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Time frame: Baseline, Week 48
Population: Participants in the Full Analysis Set only from Part B (Hepatic Impairment) were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Change From Baseline in CPT Score in Hepatically Impaired Participants at Week 48 | 0 units on a scale | Standard Deviation 1.1 |
Secondary
Change From Baseline in CPT Score in Hepatically Impaired Participants at Week 96
CPT scores grade the severity of cirrhosis and are used to determine the need for liver transplantation. Scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Time frame: Baseline, Week 96
Population: Participants in the Full Analysis Set only from Part B (Hepatic Impairment) with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Change From Baseline in CPT Score in Hepatically Impaired Participants at Week 96 | 0 units on a scale | Standard Deviation 1.2 |
Secondary
Change From Baseline in eGFRcg in Participants With Moderate or Severe Renal Impairment and Hepatically Impaired Participants at Week 48
GFR is a measure of the rate at which blood is filtered by the kidney. Cockcroft-Gault is an equation (calculation) used to estimate GFR based on serum creatinine, weight, and gender. eGFRcg = (140 - age in years) x (body weight in kg) x (0.85 if female) divided by 72 x serum creatinine in mg/dL. Moderate renal impairment= 30 mL/min ≤ eGFRCG ≤ 59 mL/min Severe renal impairment= 15 mL/min ≤ eGFRCG \< 30 mL/min Change from baseline was calculated as the value at Week 48 minus the value at Baseline.
Time frame: Baseline, Week 48
Population: Participants in the Safety Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Change From Baseline in eGFRcg in Participants With Moderate or Severe Renal Impairment and Hepatically Impaired Participants at Week 48 | -0.5 mL/min |
| Part A (Renal Impairment): End Stage Renal Disease | Change From Baseline in eGFRcg in Participants With Moderate or Severe Renal Impairment and Hepatically Impaired Participants at Week 48 | 1.2 mL/min |
Secondary
Change From Baseline in eGFRcg in Participants With Moderate or Severe Renal Impairment and Hepatically Impaired Participants at Week 96
GFR is a measure of the rate at which blood is filtered by the kidney. Cockcroft-Gault is an equation (calculation) used to estimate GFR based on serum creatinine, weight, and gender. eGFRcg = (140 - age in years) x (body weight in kg) x (0.85 if female) divided by 72 x serum creatinine in mg/dL. Moderate renal impairment= 30 mL/min ≤ eGFRCG ≤ 59 mL/min Severe renal impairment= 15 mL/min ≤ eGFRCG \< 30 mL/min Change from baseline was calculated as the value at Week 96 minus the value at Baseline.
Time frame: Baseline, Week 96
Population: Participants in the Safety Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Change From Baseline in eGFRcg in Participants With Moderate or Severe Renal Impairment and Hepatically Impaired Participants at Week 96 | 1.0 mL/min |
| Part A (Renal Impairment): End Stage Renal Disease | Change From Baseline in eGFRcg in Participants With Moderate or Severe Renal Impairment and Hepatically Impaired Participants at Week 96 | -2.4 mL/min |
Secondary
Change From Baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFRcg) in Participants With Moderate or Severe Renal Impairment and Hepatically Impaired Participants at Week 24
GFR is a measure of the rate at which blood is filtered by the kidney. Cockcroft-Gault is an equation (calculation) used to estimate GFR based on serum creatinine, weight, and gender. eGFRcg = (140 - age in years) x (body weight in kg) x (0.85 if female) divided by 72 x serum creatinine in mg/dL. Moderate renal impairment= 30 mL/min ≤ eGFRCG ≤ 59 mL/min Severe renal impairment= 15 mL/min ≤ eGFRCG \< 30 mL/min Change from baseline was calculated as the value at Week 24 minus the value at Baseline.
Time frame: Baseline, Week 24
Population: Participants in the Safety Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Change From Baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFRcg) in Participants With Moderate or Severe Renal Impairment and Hepatically Impaired Participants at Week 24 | -0.4 mL/min |
| Part A (Renal Impairment): End Stage Renal Disease | Change From Baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFRcg) in Participants With Moderate or Severe Renal Impairment and Hepatically Impaired Participants at Week 24 | 1.9 mL/min |
Secondary
Change From Baseline in FibroTest® Score at Week 24
The FibroTest® score is used to assess liver fibrosis. Scores range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis. Change from baseline was calculated as the value at Week 24 minus the value at Baseline.
Time frame: Baseline, Week 24
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Change From Baseline in FibroTest® Score at Week 24 | -0.01 units on a scale | Standard Deviation 0.099 |
| Part A (Renal Impairment): End Stage Renal Disease | Change From Baseline in FibroTest® Score at Week 24 | -0.01 units on a scale | Standard Deviation 0.064 |
| Part B: Hepatic Impairment | Change From Baseline in FibroTest® Score at Week 24 | -0.05 units on a scale | Standard Deviation 0.106 |
Secondary
Change From Baseline in FibroTest® Score at Week 48
The FibroTest® score is used to assess liver fibrosis. Scores range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis. Change from baseline was calculated as the value at Week 48 minus the value at Baseline.
Time frame: Baseline, Week 48
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Change From Baseline in FibroTest® Score at Week 48 | -0.03 units on a scale | Standard Deviation 0.102 |
| Part A (Renal Impairment): End Stage Renal Disease | Change From Baseline in FibroTest® Score at Week 48 | -0.01 units on a scale | Standard Deviation 0.071 |
| Part B: Hepatic Impairment | Change From Baseline in FibroTest® Score at Week 48 | -0.03 units on a scale | Standard Deviation 0.102 |
Secondary
Change From Baseline in FibroTest® Score at Week 96
The FibroTest® score is used to assess liver fibrosis. Scores range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis. Change from baseline was calculated as the value at Week 96 minus the value at Baseline.
Time frame: Week 96
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Change From Baseline in FibroTest® Score at Week 96 | -0.01 units on a scale | Standard Deviation 0.114 |
| Part A (Renal Impairment): End Stage Renal Disease | Change From Baseline in FibroTest® Score at Week 96 | 0.03 units on a scale | Standard Deviation 0.107 |
| Part B: Hepatic Impairment | Change From Baseline in FibroTest® Score at Week 96 | -0.02 units on a scale | Standard Deviation 0.118 |
Secondary
Change From Baseline in MELD Score in Hepatically Impaired Participants at Week 48
MELD scores are used to assess prognosis and suitability for liver transplantation. Scores can range from 6 to 40, with higher scores indicating greater disease severity.
Time frame: Baseline, Week 48
Population: Participants in the Full Analysis Set only from Part B (Hepatic Impairment) with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Change From Baseline in MELD Score in Hepatically Impaired Participants at Week 48 | 0.1 units on a scale | Standard Deviation 2.35 |
Secondary
Change From Baseline in MELD Score in Hepatically Impaired Participants at Week 96
MELD scores are used to assess prognosis and suitability for liver transplantation. Scores can range from 6 to 40, with higher scores indicating greater disease severity.
Time frame: Baseline, Week 96
Population: Participants in the Full Analysis Set only from Part B (Hepatic Impairment) with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Change From Baseline in MELD Score in Hepatically Impaired Participants at Week 96 | -1.0 units on a scale | Standard Deviation 1.61 |
Secondary
Change From Baseline in Model for End-Stage Liver Disease (MELD) Score in Hepatically Impaired Participants at Week 24
MELD scores are used to assess prognosis and suitability for liver transplantation. Scores can range from 6 to 40, with higher scores indicating greater disease severity.
Time frame: Baseline, Week 24
Population: Participants in the Full Analysis Set only from Part B (Hepatic Impairment) were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Change From Baseline in Model for End-Stage Liver Disease (MELD) Score in Hepatically Impaired Participants at Week 24 | -0.6 units on a scale | Standard Deviation 1.94 |
Secondary
Percentage of Participants Achieving Virologic Response (Plasma HBV DNA < 20 IU/mL) at Week 48
The percentage of participants with HBV DNA \< 20 IU/mL at Week 48 was determined by the Missing = Failure (M = F) approach.
Time frame: Weeks 48
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants Achieving Virologic Response (Plasma HBV DNA < 20 IU/mL) at Week 48 | 92.3 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants Achieving Virologic Response (Plasma HBV DNA < 20 IU/mL) at Week 48 | 93.3 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants Achieving Virologic Response (Plasma HBV DNA < 20 IU/mL) at Week 48 | 100.0 percentage of participants |
Secondary
Percentage of Participants Achieving Virologic Response (Plasma HBV DNA < 20 IU/mL) at Week 96
The percentage of participants with HBV DNA \< 20 IU/mL at Week 48 was determined by the Missing = Failure (M = F) approach.
Time frame: Weeks 96
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants Achieving Virologic Response (Plasma HBV DNA < 20 IU/mL) at Week 96 | 83.3 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants Achieving Virologic Response (Plasma HBV DNA < 20 IU/mL) at Week 96 | 86.7 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants Achieving Virologic Response (Plasma HBV DNA < 20 IU/mL) at Week 96 | 77.4 percentage of participants |
Secondary
Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 48
Treatment-emergent AEs were defined as: Any AEs with an onset date on or after the study drug start date and no later than the study drug stop date + 3 days after permanent discontinuation of study drug; Any AEs with onset date on or after the study drug start date for those who have not permanently discontinued study drug; Any AEs leading to premature discontinuation of study drug. The most severe graded AE from all tests was counted for each participant.
Time frame: Week 48
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 48 | Any Treatment-emergent AE | 71.8 percentage of participants |
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 48 | Grade 3 and Above Treatment-emergent AEs | 15.4 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 48 | Any Treatment-emergent AE | 86.7 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 48 | Grade 3 and Above Treatment-emergent AEs | 20.0 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 48 | Any Treatment-emergent AE | 71.0 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 48 | Grade 3 and Above Treatment-emergent AEs | 12.9 percentage of participants |
Secondary
Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 96
Treatment-emergent AEs were defined as: Any AEs with an onset date on or after the study drug start date and no later than the study drug stop date + 3 days after permanent discontinuation of study drug; Any AEs with onset date on or after the study drug start date for those who have not permanently discontinued study drug; Any AEs leading to premature discontinuation of study drug. The most severe graded AE from all tests was counted for each participant.
Time frame: Week 96
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 96 | Any Treatment-emergent AEs | 74.4 percentage of participants |
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 96 | Grade 3 and Above treatment-emergent AEs | 17.9 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 96 | Any Treatment-emergent AEs | 100.0 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 96 | Grade 3 and Above treatment-emergent AEs | 26.7 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 96 | Any Treatment-emergent AEs | 77.4 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 96 | Grade 3 and Above treatment-emergent AEs | 25.8 percentage of participants |
Secondary
Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 48
Graded treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any postbaseline visit, up to and including the date of last dose of study drug + 3 days for participants who permanently discontinued study drug or the last available date in the database snapshot for participants who were on treatment at the time of the analysis. The most severe graded abnormality from all tests was counted for each participant.
Time frame: Week 48
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 48 | Grade 3 | 12.8 percentage of participants |
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 48 | Any Graded Laboratory Abnormality | 96.2 percentage of participants |
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 48 | Grade 4 | 0 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 48 | Grade 3 | 40.0 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 48 | Any Graded Laboratory Abnormality | 100.0 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 48 | Grade 4 | 26.7 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 48 | Any Graded Laboratory Abnormality | 90.3 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 48 | Grade 4 | 9.7 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 48 | Grade 3 | 41.9 percentage of participants |
Secondary
Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 96
Graded treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any post-baseline visit, up to and including the date of last dose of study drug + 3 days for participants who permanently discontinued study drug or the last available date in the database snapshot for participants who were on treatment at the time of the analysis. The most severe graded abnormality from all tests was counted for each participant.
Time frame: Week 96
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 96 | Grade 3 | 15.4 percentage of particpants |
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 96 | Any Graded Laboratory Abnormality | 96.2 percentage of particpants |
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 96 | Grade 4 | 1.3 percentage of particpants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 96 | Grade 3 | 46.7 percentage of particpants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 96 | Any Graded Laboratory Abnormality | 100.0 percentage of particpants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 96 | Grade 4 | 26.7 percentage of particpants |
| Part B: Hepatic Impairment | Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 96 | Any Graded Laboratory Abnormality | 100.0 percentage of particpants |
| Part B: Hepatic Impairment | Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 96 | Grade 4 | 12.9 percentage of particpants |
| Part B: Hepatic Impairment | Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 96 | Grade 3 | 41.9 percentage of particpants |
Secondary
Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Week 24 by Central Laboratory and the American Association for the Study of Liver Diseases (AASLD) Criteria
Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to \< 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to \< 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. The M = F approach was used for this analysis.
Time frame: Week 24
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Week 24 by Central Laboratory and the American Association for the Study of Liver Diseases (AASLD) Criteria | ALT by central laboratory | 92.3 percentage of participants |
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Week 24 by Central Laboratory and the American Association for the Study of Liver Diseases (AASLD) Criteria | ALT by AASLD criteria | 87.2 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Week 24 by Central Laboratory and the American Association for the Study of Liver Diseases (AASLD) Criteria | ALT by central laboratory | 93.3 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Week 24 by Central Laboratory and the American Association for the Study of Liver Diseases (AASLD) Criteria | ALT by AASLD criteria | 93.3 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Week 24 by Central Laboratory and the American Association for the Study of Liver Diseases (AASLD) Criteria | ALT by central laboratory | 83.9 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Week 24 by Central Laboratory and the American Association for the Study of Liver Diseases (AASLD) Criteria | ALT by AASLD criteria | 80.6 percentage of participants |
Secondary
Percentage of Participants With Normal ALT at Week 48 by Central Laboratory and the AASLD Criteria
Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to \< 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to \< 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. The M = F approach was used for this analysis.
Time frame: Week 48
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Normal ALT at Week 48 by Central Laboratory and the AASLD Criteria | ALT by central laboratory | 89.7 percentage of participants |
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Normal ALT at Week 48 by Central Laboratory and the AASLD Criteria | ALT by AASLD criteria | 87.2 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants With Normal ALT at Week 48 by Central Laboratory and the AASLD Criteria | ALT by central laboratory | 86.7 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants With Normal ALT at Week 48 by Central Laboratory and the AASLD Criteria | ALT by AASLD criteria | 80.0 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Normal ALT at Week 48 by Central Laboratory and the AASLD Criteria | ALT by central laboratory | 90.3 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Normal ALT at Week 48 by Central Laboratory and the AASLD Criteria | ALT by AASLD criteria | 80.6 percentage of participants |
Secondary
Percentage of Participants With Normal ALT at Week 96 by Central Laboratory and the AASLD Criteria
Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to \< 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to \< 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. The M = F approach was used for this analysis.
Time frame: Week 96
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Normal ALT at Week 96 by Central Laboratory and the AASLD Criteria | ALT by AASLD criteria | 74.4 percentage of participants |
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Normal ALT at Week 96 by Central Laboratory and the AASLD Criteria | ALT by central laboratory | 82.1 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants With Normal ALT at Week 96 by Central Laboratory and the AASLD Criteria | ALT by central laboratory | 86.7 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants With Normal ALT at Week 96 by Central Laboratory and the AASLD Criteria | ALT by AASLD criteria | 86.7 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Normal ALT at Week 96 by Central Laboratory and the AASLD Criteria | ALT by central laboratory | 71.0 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Normal ALT at Week 96 by Central Laboratory and the AASLD Criteria | ALT by AASLD criteria | 58.1 percentage of participants |
Secondary
Percentage of Participants With Normalized ALT at Week 24 by Central Laboratory and the AASLD Criteria
ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit. Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to \< 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to \< 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. The M = F approach was used for this analysis.
Time frame: Week 24
Population: Participants in the Full Analysis Set with Baseline ALT \> ULN were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Normalized ALT at Week 24 by Central Laboratory and the AASLD Criteria | Normalized ALT by Central Laboratory | 66.7 percentage of participants |
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Normalized ALT at Week 24 by Central Laboratory and the AASLD Criteria | Normalized ALT by AASLD Criteria | 40.0 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Normalized ALT at Week 24 by Central Laboratory and the AASLD Criteria | Normalized ALT by AASLD Criteria | 60.0 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Normalized ALT at Week 24 by Central Laboratory and the AASLD Criteria | Normalized ALT by Central Laboratory | 50.0 percentage of participants |
Secondary
Percentage of Participants With Normalized ALT at Week 48 by Central Laboratory and the AASLD Criteria
ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit. Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to \< 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to \< 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. The M = F approach was used for this analysis.
Time frame: Week 48
Population: Participants in the Full Analysis Set with Baseline ALT \> ULN were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Normalized ALT at Week 48 by Central Laboratory and the AASLD Criteria | Normalized ALT by Central Laboratory | 33.3 percentage of participants |
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Normalized ALT at Week 48 by Central Laboratory and the AASLD Criteria | Normalized ALT by AASLD Criteria | 60.0 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Normalized ALT at Week 48 by Central Laboratory and the AASLD Criteria | Normalized ALT by Central Laboratory | 75.0 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Normalized ALT at Week 48 by Central Laboratory and the AASLD Criteria | Normalized ALT by AASLD Criteria | 60.0 percentage of participants |
Secondary
Percentage of Participants With Normalized ALT at Week 96 by Central Laboratory and the AASLD Criteria
ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit. Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to \< 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to \< 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. The M = F approach was used for this analysis.
Time frame: Week 96
Population: Participants in the Full Analysis Set with Baseline ALT \> ULN were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Normalized ALT at Week 96 by Central Laboratory and the AASLD Criteria | Normalized ALT by AASLD Criteria | 20.0 percentage of participants |
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Normalized ALT at Week 96 by Central Laboratory and the AASLD Criteria | Normalized ALT by Central Laboratory | 33.3 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Normalized ALT at Week 96 by Central Laboratory and the AASLD Criteria | Normalized ALT by Central Laboratory | 50.0 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Normalized ALT at Week 96 by Central Laboratory and the AASLD Criteria | Normalized ALT by AASLD Criteria | 50.0 percentage of participants |
Secondary
Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (≥ LLOD) at Week 48
The percentage of participants with HBV DNA \< 20 IU/mL and target detected (≥ LLOD; i.e. 10 IU/mL) at Week 48 was determined by the M = F approach.
Time frame: Week 48
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (≥ LLOD) at Week 48 | 26.9 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (≥ LLOD) at Week 48 | 26.7 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (≥ LLOD) at Week 48 | 25.8 percentage of participants |
Secondary
Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (≥ LLOD) at Week 96
The percentage of participants with HBV DNA \< 20 IU/mL and target detected (≥ LLOD; i.e. 10 IU/mL) at Week 96 was determined by the M = F approach.
Time frame: Week 96
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (≥ LLOD) at Week 96 | 14.1 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (≥ LLOD) at Week 96 | 20.0 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (≥ LLOD) at Week 96 | 0 percentage of participants |
Secondary
Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (≥ Lower Limit of Detection [LLOD]) at Week 24
The percentage of participants with HBV DNA \< 20 IU/mL and target detected (≥ LLOD; i.e. 10 IU/mL) at Week 24 was determined by the M = F approach.
Time frame: Week 24
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (≥ Lower Limit of Detection [LLOD]) at Week 24 | 21.8 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (≥ Lower Limit of Detection [LLOD]) at Week 24 | 40.0 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (≥ Lower Limit of Detection [LLOD]) at Week 24 | 22.6 percentage of participants |
Secondary
Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 24
The percentage of participants with HBV DNA \< 20 IU/mL and target not detected (\< LLOD; i.e. 10 IU/mL) at Week 24 was determined by the M = F approach.
Time frame: Week 24
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 24 | 75.6 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 24 | 60.0 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 24 | 77.4 percentage of participants |
Secondary
Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 48
The percentage of participants with HBV DNA \< 20 IU/mL and target not detected (\< LLOD; i.e. 10 IU/mL) at Week 48 was determined by the M = F approach.
Time frame: Weeks 48
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 48 | 65.4 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 48 | 66.7 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 48 | 74.2 percentage of participants |
Secondary
Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 96
The percentage of participants with HBV DNA \< 20 IU/mL and target not detected (\< LLOD; i.e. 10 IU/mL) at Week 96 was determined by the M = F approach.
Time frame: Weeks 96
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 96 | 69.2 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 96 | 66.7 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 96 | 77.4 percentage of participants |
Secondary
Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 24
HBeAg loss was defined as HBeAg changing from positive at baseline to negative at a postbaseline. The M = F approach was used for this analysis.
Time frame: Week 24
Population: The Serologically Evaluable Full Analysis Set for HBeAg Loss/Seroconversion included all participants who were enrolled and received at least 1 dose of study drug, and with HBeAg positive and HBeAb negative or missing at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 24 | 0 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 24 | 0 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 24 | 0 percentage of participants |
Secondary
Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 48
HBeAg loss was defined as HBeAg changing from positive at baseline to negative at a postbaseline. The M = F approach was used for this analysis.
Time frame: Week 48
Population: Participants in the Serologically Evaluable Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 48 | 0 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 48 | 0 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 48 | 0 percentage of participants |
Secondary
Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 96
HBeAg loss was defined as HBeAg changing from positive at baseline to negative at a postbaseline. The M = F approach was used for this analysis.
Time frame: Week 96
Population: The Serologically Evaluable Full Analysis Set for HBeAg Loss/Seroconversion included all participants who were enrolled and received at least 1 dose of study drug, and with HBeAg positive and HBeAb negative or missing at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 96 | 0 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 96 | 33.3 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 96 | 0 percentage of participants |
Secondary
Percentage of Participants With Serological Response: Loss of HBsAg at Week 48
HBsAg loss was defined as HBsAg changing from positive at baseline to negative at a postbaseline. The M = F approach was used for this analysis.
Time frame: Week 48
Population: Participants in the Serologically Evaluable Full Analysis Set for HBsAg Loss/Seroconversion with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Serological Response: Loss of HBsAg at Week 48 | 0.0 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants With Serological Response: Loss of HBsAg at Week 48 | 6.7 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Serological Response: Loss of HBsAg at Week 48 | 3.3 percentage of participants |
Secondary
Percentage of Participants With Serological Response: Loss of HBsAg at Week 96
HBsAg loss was defined as HBsAg changing from positive at baseline to negative at a postbaseline. The M = F approach was used for this analysis.
Time frame: Week 96
Population: Participants in the Serologically Evaluable Full Analysis Set for HBsAg Loss/Seroconversion with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Serological Response: Loss of HBsAg at Week 96 | 0 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants With Serological Response: Loss of HBsAg at Week 96 | 0 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Serological Response: Loss of HBsAg at Week 96 | 6.7 percentage of participants |
Secondary
Percentage of Participants With Serological Response: Loss of Hepatitis B s-Antigen (HBsAg) at Week 24
HBsAg loss was defined as HBsAg changing from positive at baseline to negative at a postbaseline. The M = F approach was used for this analysis.
Time frame: Week 24
Population: The Serologically Evaluable Full Analysis Set for HBsAg Loss/Seroconversion (all participants who were enrolled and received at least 1 dose of study drug, and with HBsAg positive and HBsAb negative or missing at baseline) with available data were analyzed..
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Serological Response: Loss of Hepatitis B s-Antigen (HBsAg) at Week 24 | 0 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants With Serological Response: Loss of Hepatitis B s-Antigen (HBsAg) at Week 24 | 0 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Serological Response: Loss of Hepatitis B s-Antigen (HBsAg) at Week 24 | 0 percentage of participants |
Secondary
Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 24
HBeAg seroconversion was defined as HBeAg loss and HBeAb test changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.
Time frame: Week 24
Population: The Serologically Evaluable Full Analysis Set for HBeAg Loss/Seroconversion were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 24 | 0 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 24 | 0 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 24 | 0 percentage of participants |
Secondary
Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 48
HBeAg seroconversion was defined as HBeAg loss and HBeAb test changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.
Time frame: Week 48
Population: The Serologically Evaluable Full Analysis Set for HBeAg Loss/Seroconversion were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 48 | 0 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 48 | 0 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 48 | 0 percentage of participants |
Secondary
Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 96
HBeAg seroconversion was defined as HBeAg loss and HBeAb test changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.
Time frame: Week 96
Population: The Serologically Evaluable Full Analysis Set for HBeAg Loss/Seroconversion were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 96 | 0 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 96 | 33.3 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 96 | 0 percentage of participants |
Secondary
Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 24
HBsAg seroconversion was defined as HBsAg loss and HBsAb test changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.
Time frame: Week 24
Population: The Serologically Evaluable Full Analysis Set for HBsAg Loss/Seroconversion were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 24 | 0 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 24 | 0 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 24 | 0 percentage of participants |
Secondary
Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 48
HBsAg seroconversion was defined as HBsAg loss and HBsAb test changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.
Time frame: Week 48
Population: Participants in the Serologically Evaluable Full Analysis Set for HBsAg Loss/Seroconversion were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 48 | 0 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 48 | 0 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 48 | 0 percentage of participants |
Secondary
Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 96
HBsAg seroconversion was defined as HBsAg loss and HBsAb test changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.
Time frame: Week 96
Population: The Serologically Evaluable Full Analysis Set for HBsAg Loss/Seroconversion were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 96 | 0 percentage of participants |
| Part A (Renal Impairment): End Stage Renal Disease | Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 96 | 0 percentage of participants |
| Part B: Hepatic Impairment | Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 96 | 0 percentage of participants |
Secondary
Percent Change From Baseline in Hip BMD at Week 48
Percent change = Change from baseline at a postbaseline visit/baseline \* 100%.
Time frame: Baseline, Week 48
Population: Participants in Hip DXA Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percent Change From Baseline in Hip BMD at Week 48 | 0.565 percent change | Standard Deviation 2.616 |
| Part A (Renal Impairment): End Stage Renal Disease | Percent Change From Baseline in Hip BMD at Week 48 | -1.075 percent change | Standard Deviation 3.6355 |
| Part B: Hepatic Impairment | Percent Change From Baseline in Hip BMD at Week 48 | -0.221 percent change | Standard Deviation 3.0158 |
Secondary
Percent Change From Baseline in Hip BMD at Week 96
Percent change = Change from baseline at a postbaseline visit/baseline \* 100%.
Time frame: Baseline, Week 96
Population: Participants in Hip DXA Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percent Change From Baseline in Hip BMD at Week 96 | 0.425 percent change | Standard Deviation 2.8381 |
| Part A (Renal Impairment): End Stage Renal Disease | Percent Change From Baseline in Hip BMD at Week 96 | -0.834 percent change | Standard Deviation 4.7171 |
| Part B: Hepatic Impairment | Percent Change From Baseline in Hip BMD at Week 96 | 0.277 percent change | Standard Deviation 3.2549 |
Secondary
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 24
Percent change = Change from baseline at a postbaseline visit/baseline \* 100%.
Time frame: Baseline, Week 24
Population: Participants in the Hip Dual-Energy X-Ray Absorptiometry (DXA) Analysis Set (all participants who were enrolled and received at least 1 dose of study drug and had non-missing baseline hip BMD values) with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 24 | 0.135 percent change | Standard Deviation 1.8348 |
| Part A (Renal Impairment): End Stage Renal Disease | Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 24 | 0.322 percent change | Standard Deviation 2.1835 |
| Part B: Hepatic Impairment | Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 24 | 0.322 percent change | Standard Deviation 2.5105 |
Secondary
Percent Change From Baseline in Spine BMD at Week 24
Percent change = Change from baseline at a postbaseline visit/baseline \* 100%.
Time frame: Baseline, Week 24
Population: Participants in the Spine DXA Analysis Set (all participants who were enrolled and received at least 1 dose of study drug and had non-missing baseline spine BMD values) with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percent Change From Baseline in Spine BMD at Week 24 | 1.229 percent change | Standard Deviation 3.4252 |
| Part A (Renal Impairment): End Stage Renal Disease | Percent Change From Baseline in Spine BMD at Week 24 | 0.683 percent change | Standard Deviation 3.137 |
| Part B: Hepatic Impairment | Percent Change From Baseline in Spine BMD at Week 24 | 1.258 percent change | Standard Deviation 2.3416 |
Secondary
Percent Change From Baseline in Spine BMD at Week 48
Percent change = Change from baseline at a postbaseline visit/baseline \* 100%.
Time frame: Baseline, Week 48
Population: Participants in the Spine DXA Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percent Change From Baseline in Spine BMD at Week 48 | 1.516 percent change | Standard Deviation 3.7486 |
| Part A (Renal Impairment): End Stage Renal Disease | Percent Change From Baseline in Spine BMD at Week 48 | 0.016 percent change | Standard Deviation 4.1636 |
| Part B: Hepatic Impairment | Percent Change From Baseline in Spine BMD at Week 48 | 0.535 percent change | Standard Deviation 3.4386 |
Secondary
Percent Change From Baseline in Spine BMD at Week 96
Percent change = Change from baseline at a postbaseline visit/baseline \* 100%.
Time frame: Baseline, Week 96
Population: Participants in the Spine DXA Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Percent Change From Baseline in Spine BMD at Week 96 | 1.293 percent change | Standard Deviation 4.4136 |
| Part A (Renal Impairment): End Stage Renal Disease | Percent Change From Baseline in Spine BMD at Week 96 | -0.283 percent change | Standard Deviation 4.5327 |
| Part B: Hepatic Impairment | Percent Change From Baseline in Spine BMD at Week 96 | -0.249 percent change | Standard Deviation 3.9127 |