Study to Evaluate the Safety and Efficacy of Switching to Tenofovir Alafenamide (TAF) From Tenofovir Disoproxil Fumarate (TDF) and/or Other Oral Antiviral Treatment (OAV)
Sponsor
Gilead Sciences (Industry)
Overall Status
Completed
CT.gov ID
NCT03180619
Collaborator
(none)
124
30
3
38.2
4.1
0.1
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
124 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Open-label Study to Evaluate the Safety and Efficacy of Switching to Tenofovir Alafenamide (TAF) From Tenofovir Disoproxil Fumarate (TDF) and/or Other Oral Antiviral Treatment (OAV) in Virologically Suppressed Chronic Hepatitis B Subjects With Renal and/or Hepatic Impairment
Actual Study Start Date
:
Jun 29, 2017
Actual Primary Completion Date
:
Mar 27, 2019
Actual Study Completion Date
:
Sep 4, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part A (Renal Impairment): Moderate or Severe Renal Impairment Participants with chronic hepatitis B (CHB) and moderate or severe renal impairment who were virologically suppressed and taking tenofovir disoproxil fumarate (TDF), a TDF-containing anti-hepatitis B virus (HBV) regimen, or other oral antivirals (OAVs), will switch to tenofovir alafenamide (TAF) and receive TAF 25 milligram (mg) tablet once daily orally for 96 weeks. |
Drug: TAF
Tablet administered orally once daily
Other Names:
|
| Experimental: 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, will switch to TAF and receive TAF 25 mg tablet once daily orally for 96 weeks. |
Drug: TAF
Tablet administered orally once daily
Other Names:
|
| Experimental: 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, will switch to TAF and receive TAF 25 mg tablet once daily orally for 96 weeks. |
Drug: TAF
Tablet administered orally once daily
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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.
- 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 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: 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 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.
- 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.
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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/Exclusion criteria may apply.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Coalition of Inclusive Medicine | Los Angeles | California | United States | 90020 |
| 2 | Silicon Valley Research Institute, Inc | San Jose | California | United States | 95128 |
| 3 | Henry Ford Health System | Detroit | Michigan | United States | 48202 |
| 4 | Harborview Medical Center | Seattle | Washington | United States | 98104 |
| 5 | University of Calgary Liver Unit | Calgary | Canada | T2N4Z6 | |
| 6 | Centre de Recherche du Centre Hospitalier de l'Universite de Montreal | Montreal | Canada | H2X 0A9 | |
| 7 | University Health Network,Toronto general Hospital,Toronto centre for liver disease | Toronto | Canada | M5G 2C4 | |
| 8 | Toronto Liver Centre | Toronto | Canada | M6H 3M1 | |
| 9 | (G.I.R.I.) GI Research Institute | Vancouver | Canada | V6Z 2K5 | |
| 10 | Prince of Wales Hospital | Shatin | NT | Hong Kong | |
| 11 | Princess Margaret Hospital | Kowloon | Hong Kong | ||
| 12 | Alice Ho Miu Ling Nethersole Hospital | Tai Po | Hong Kong | ||
| 13 | U.O. Medicina Generale Epatologia IRCCS Humanitas Centro di Ricerca Traslazionale in Epatologia | Rozzano | Milan | Italy | 20089 |
| 14 | Dipartimento di Scienze Mediche e Chirurgiche (DIMEC) AOU Policlinico S.Orsola-Malpighi di Bologna | Bologna | Italy | 40138 | |
| 15 | UOC Gastroenterol-Epatol.-Fondazione IRCCS Ca Granda | Milan | Italy | 20122 | |
| 16 | Dong-A University Hospital | Busan | Korea, Republic of | 49201 | |
| 17 | Pusan National University Hospital | Busan | Korea, Republic of | 49241 | |
| 18 | Asan Medical Center | Seoul | Korea, Republic of | 05505 | |
| 19 | Yonsei University Health System, Severance Hospital | Seoul | Korea, Republic of | 120-752 | |
| 20 | Auckland Clinical Studies | Grafton | Auckland | New Zealand | 1010 |
| 21 | Changhua Christian Hospital | Changhua | Taiwan | 500 | |
| 22 | Ditmanson Medical Foundation Chia-Yi Christian Hospital | Chiayi City | Taiwan | 60002 | |
| 23 | Kaohsiung Chang Gung Memorial Hospital | Kaohsiung City | Taiwan | 83301 | |
| 24 | Kaohsiung Medical University Chung-Ho Memorial Hospital | Kaohsiung | Taiwan | 807 | |
| 25 | Taichung Veterans Genl Hosp | Taichung | Taiwan | 40705 | |
| 26 | National Taiwan University Hospital | Taipei | Taiwan | 10001 | |
| 27 | Veterans General Hospital-Taipei | Taipei | Taiwan | 11217 | |
| 28 | Chang Gung Medical Foundation, Linkou Chang Gung Memorial Hospital | Taoyuan City | Taiwan | 333 | |
| 29 | Nottingham University Hospital | London | United Kingdom | NG7 2UH | |
| 30 | King's College Hospital NHS Foundation Trust | London | United Kingdom | SE5 9RS |
Sponsors and Collaborators
- Gilead Sciences
Investigators
- Study Director: Gilead Study Director, Gilead Sciences
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT03180619
Other Study ID Numbers:
- GS-US-320-4035
- 2016-004625-16
First Posted:
Jun 8, 2017
Last Update Posted:
Sep 27, 2021
Last Verified:
Aug 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
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 Detail | 147 participants were screened. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | Participants with chronic hepatitis B (CHB) and moderate or severe renal impairment who were virologically suppressed and took tenofovir disoproxil fumarate (TDF), a TDF-containing anti-hepatitis B virus (HBV) regimen, or other oral antivirals (OAVs), switched to tenofovir alafenamide (TAF) and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and end stage renal disease who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and moderate or severe hepatic impairment who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. |
| Period Title: Overall Study | |||
| STARTED | 78 | 15 | 31 |
| COMPLETED | 67 | 14 | 25 |
| NOT COMPLETED | 11 | 1 | 6 |
Baseline Characteristics
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment | Total |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | Total of all reporting groups |
| Overall Participants | 78 | 15 | 31 | 124 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
66
(10.1)
|
54
(12.8)
|
55
(10.8)
|
61
(11.8)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
21
26.9%
|
3
20%
|
10
32.3%
|
34
27.4%
|
| Male |
57
73.1%
|
12
80%
|
21
67.7%
|
90
72.6%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| Hispanic or Latino |
0
0%
|
0
0%
|
1
3.2%
|
1
0.8%
|
| Not Hispanic or Latino |
78
100%
|
15
100%
|
30
96.8%
|
123
99.2%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| Asian |
59
75.6%
|
13
86.7%
|
25
80.6%
|
97
78.2%
|
| Black or African American |
3
3.8%
|
0
0%
|
1
3.2%
|
4
3.2%
|
| Native Hawaiian or Pacific Islander |
0
0%
|
2
13.3%
|
0
0%
|
2
1.6%
|
| White |
15
19.2%
|
0
0%
|
4
12.9%
|
19
15.3%
|
| Other |
1
1.3%
|
0
0%
|
1
3.2%
|
2
1.6%
|
| Region of Enrollment (Count of Participants) | ||||
| New Zealand |
0
0%
|
2
13.3%
|
0
0%
|
2
1.6%
|
| Canada |
22
28.2%
|
0
0%
|
3
9.7%
|
25
20.2%
|
| South Korea |
12
15.4%
|
3
20%
|
5
16.1%
|
20
16.1%
|
| Hong Kong |
14
17.9%
|
1
6.7%
|
2
6.5%
|
17
13.7%
|
| United States |
3
3.8%
|
0
0%
|
7
22.6%
|
10
8.1%
|
| Taiwan |
13
16.7%
|
9
60%
|
11
35.5%
|
33
26.6%
|
| Italy |
13
16.7%
|
0
0%
|
2
6.5%
|
15
12.1%
|
| United Kingdom |
1
1.3%
|
0
0%
|
1
3.2%
|
2
1.6%
|
| Alanine Aminotransferase (ALT) (Units/Liter (U/L)) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Units/Liter (U/L)] |
20
(9.6)
|
14
(5.2)
|
28
(12.4)
|
21
(10.8)
|
| ALT Level Based on Central Lab Normal Range (Count of Participants) | ||||
| ≤ ULN |
75
96.2%
|
15
100%
|
27
87.1%
|
117
94.4%
|
| > ULN - 5xULN |
3
3.8%
|
0
0%
|
4
12.9%
|
7
5.6%
|
| > 5xULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| ALT Level Based on 2018 American Association for the Study of Liver Diseases (AASLD) Normal Range (Count of Participants) | ||||
| ≤ ULN |
73
93.6%
|
15
100%
|
21
67.7%
|
109
87.9%
|
| > ULN - 5xULN |
5
6.4%
|
0
0%
|
10
32.3%
|
15
12.1%
|
| > 5xULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Categories (Count of Participants) | ||||
| < 20 IU/mL |
77
98.7%
|
14
93.3%
|
31
100%
|
122
98.4%
|
| ≥ 20 IU/mL - < 69 IU/mL |
0
0%
|
1
6.7%
|
0
0%
|
1
0.8%
|
| ≥ 69 IU/mL |
1
1.3%
|
0
0%
|
0
0%
|
1
0.8%
|
| Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFRcg) (milliliter/minute (mL/min)) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [milliliter/minute (mL/min)] |
45.5
(10.89)
|
7.8
(2.63)
|
98.8
(33.94)
|
54.3
(34.16)
|
| Hip Bone Mineral Density (BMD) Status (Count of Participants) | ||||
| Normal (T-score ≥ -1.0) |
34
43.6%
|
3
20%
|
18
58.1%
|
55
44.4%
|
| Osteopenia (-2.5 ≤ T-score < -1.0) |
36
46.2%
|
5
33.3%
|
12
38.7%
|
53
42.7%
|
| Osteoporosis (T-score < -2.5) |
7
9%
|
7
46.7%
|
1
3.2%
|
15
12.1%
|
| Spine BMD Status (Count of Participants) | ||||
| Normal (T-score ≥ -1.0) |
37
47.4%
|
5
33.3%
|
16
51.6%
|
58
46.8%
|
| Osteopenia (-2.5 ≤ T-score < -1.0) |
22
28.2%
|
7
46.7%
|
9
29%
|
38
30.6%
|
| Osteoporosis (T-score < -2.5) |
19
24.4%
|
3
20%
|
6
19.4%
|
28
22.6%
|
| Hepatitis s-Antigen (HBsAg) (log10 IU/mL) (log10 IU/mL) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [log10 IU/mL] |
2.51
(0.782)
|
2.72
(1.405)
|
1.90
(1.169)
|
2.38
(1.012)
|
| Hepatitis B e Antigen/Antibody (HBeAg/HBeAb) Status (Count of Participants) | ||||
| Positive/Negative |
13
16.7%
|
3
20%
|
3
9.7%
|
19
15.3%
|
| Positive/Positive |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Negative/Negative |
15
19.2%
|
1
6.7%
|
10
32.3%
|
26
21%
|
| Negative/Positive |
50
64.1%
|
11
73.3%
|
18
58.1%
|
79
63.7%
|
| FibroTest® Score (units on a scale) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [units on a scale] |
0.53
(0.199)
|
0.37
(0.199)
|
0.75
(0.206)
|
0.57
(0.231)
|
| Child-Pugh-Turcotte (CPT) Score (units on a scale) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [units on a scale] |
6
(1.7)
|
6
(1.7)
|
||
| Model for End-Stage Liver Disease (MELD) Score (units on a scale) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [units on a scale] |
10.7
(3.40)
|
10.7
(3.40)
|
||
Outcome Measures
| Title | Percentage of Participants Achieving Virologic Response (Plasma Hepatitis B Virus [HBV] Deoxyribonucleic Acid [DNA] < 20 IU/mL) at Week 24 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Full Analysis Set included all participants who were enrolled and received at least 1 dose of study drug. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 78 | 15 | 31 |
| Number [percentage of participants] |
97.4
124.9%
|
100.0
666.7%
|
100.0
322.6%
|
| Title | Percentage of Participants Who Experienced Graded Treatment-Emergent Adverse Events (AEs) at Week 24 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Analysis Set included all participants who were enrolled and received at least 1 dose of study drug. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 78 | 15 | 31 |
| Any Treatment-emergent AEs |
53.8
69%
|
73.3
488.7%
|
54.8
176.8%
|
| Grade 3 and Above Treatment-emergent AEs |
6.4
8.2%
|
13.3
88.7%
|
6.5
21%
|
| Title | Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 24 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 78 | 15 | 31 |
| Any Graded Laboratory Abnormality |
96.2
123.3%
|
100.0
666.7%
|
90.3
291.3%
|
| Grade 3 and Above Laboratory Abnormality |
11.5
14.7%
|
46.7
311.3%
|
48.4
156.1%
|
| Title | Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 78 | 15 | 31 |
| Any Treatment-emergent AE |
71.8
92.1%
|
86.7
578%
|
71.0
229%
|
| Grade 3 and Above Treatment-emergent AEs |
15.4
19.7%
|
20.0
133.3%
|
12.9
41.6%
|
| Title | Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 96 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | Participants with chronic hepatitis B (CHB) and moderate or severe renal impairment who were virologically suppressed and took tenofovir disoproxil fumarate (TDF), a TDF-containing anti-hepatitis B virus (HBV) regimen, or other oral antivirals (OAVs), switched to tenofovir alafenamide (TAF) and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and end stage renal disease who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and moderate or severe hepatic impairment who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. |
| Measure Participants | 78 | 15 | 31 |
| Any Treatment-emergent AEs |
74.4
95.4%
|
100.0
666.7%
|
77.4
249.7%
|
| Grade 3 and Above treatment-emergent AEs |
17.9
22.9%
|
26.7
178%
|
25.8
83.2%
|
| Title | Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 78 | 15 | 31 |
| Any Graded Laboratory Abnormality |
96.2
123.3%
|
100.0
666.7%
|
90.3
291.3%
|
| Grade 3 |
12.8
16.4%
|
40.0
266.7%
|
41.9
135.2%
|
| Grade 4 |
0
0%
|
26.7
178%
|
9.7
31.3%
|
| Title | Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 96 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | Participants with chronic hepatitis B (CHB) and moderate or severe renal impairment who were virologically suppressed and took tenofovir disoproxil fumarate (TDF), a TDF-containing anti-hepatitis B virus (HBV) regimen, or other oral antivirals (OAVs), switched to tenofovir alafenamide (TAF) and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and end stage renal disease who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and moderate or severe hepatic impairment who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. |
| Measure Participants | 78 | 15 | 31 |
| Any Graded Laboratory Abnormality |
96.2
|
100.0
|
100.0
|
| Grade 3 |
15.4
|
46.7
|
41.9
|
| Grade 4 |
1.3
|
26.7
|
12.9
|
| Title | 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 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with available data were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part B: Hepatic Impairment |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 77 | 31 |
| Median (Inter-Quartile Range) [mL/min] |
-0.4
|
1.9
|
| Title | Change From Baseline in eGFRcg in Participants With Moderate or Severe Renal Impairment and Hepatically Impaired Participants at Week 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with available data were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part B: Hepatic Impairment |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 73 | 31 |
| Median (Inter-Quartile Range) [mL/min] |
-0.5
|
1.2
|
| Title | Change From Baseline in eGFRcg in Participants With Moderate or Severe Renal Impairment and Hepatically Impaired Participants at Week 96 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with available data were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part B: Hepatic Impairment |
|---|---|---|
| Arm/Group Description | Participants with chronic hepatitis B (CHB) and moderate or severe renal impairment who were virologically suppressed and took tenofovir disoproxil fumarate (TDF), a TDF-containing anti-hepatitis B virus (HBV) regimen, or other oral antivirals (OAVs), switched to tenofovir alafenamide (TAF) and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and moderate or severe hepatic impairment who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. |
| Measure Participants | 66 | 25 |
| Median (Inter-Quartile Range) [mL/min] |
1.0
|
-2.4
|
| Title | Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 24 |
|---|---|
| Description | Percent change = Change from baseline at a postbaseline visit/baseline * 100%. |
| Time Frame | Baseline, Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 74 | 15 | 31 |
| Mean (Standard Deviation) [percent change] |
0.135
(1.8348)
|
0.322
(2.1835)
|
0.322
(2.5105)
|
| Title | Percent Change From Baseline in Hip BMD at Week 48 |
|---|---|
| Description | Percent change = Change from baseline at a postbaseline visit/baseline * 100%. |
| Time Frame | Baseline, Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in Hip DXA Analysis Set with available data were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 72 | 14 | 31 |
| Mean (Standard Deviation) [percent change] |
0.565
(2.6160)
|
-1.075
(3.6355)
|
-0.221
(3.0158)
|
| Title | Percent Change From Baseline in Hip BMD at Week 96 |
|---|---|
| Description | Percent change = Change from baseline at a postbaseline visit/baseline * 100%. |
| Time Frame | Baseline, Week 96 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in Hip DXA Analysis Set with available data were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | Participants with chronic hepatitis B (CHB) and moderate or severe renal impairment who were virologically suppressed and took tenofovir disoproxil fumarate (TDF), a TDF-containing anti-hepatitis B virus (HBV) regimen, or other oral antivirals (OAVs), switched to tenofovir alafenamide (TAF) and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and end stage renal disease who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and moderate or severe hepatic impairment who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. |
| Measure Participants | 59 | 13 | 24 |
| Mean (Standard Deviation) [percent change] |
0.425
(2.8381)
|
-0.834
(4.7171)
|
0.277
(3.2549)
|
| Title | Percent Change From Baseline in Spine BMD at Week 24 |
|---|---|
| Description | Percent change = Change from baseline at a postbaseline visit/baseline * 100%. |
| Time Frame | Baseline, Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 76 | 15 | 31 |
| Mean (Standard Deviation) [percent change] |
1.229
(3.4252)
|
0.683
(3.1370)
|
1.258
(2.3416)
|
| Title | Percent Change From Baseline in Spine BMD at Week 48 |
|---|---|
| Description | Percent change = Change from baseline at a postbaseline visit/baseline * 100%. |
| Time Frame | Baseline, Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Spine DXA Analysis Set with available data were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 73 | 14 | 31 |
| Mean (Standard Deviation) [percent change] |
1.516
(3.7486)
|
0.016
(4.1636)
|
0.535
(3.4386)
|
| Title | Percent Change From Baseline in Spine BMD at Week 96 |
|---|---|
| Description | Percent change = Change from baseline at a postbaseline visit/baseline * 100%. |
| Time Frame | Baseline, Week 96 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Spine DXA Analysis Set with available data were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | Participants with chronic hepatitis B (CHB) and moderate or severe renal impairment who were virologically suppressed and took tenofovir disoproxil fumarate (TDF), a TDF-containing anti-hepatitis B virus (HBV) regimen, or other oral antivirals (OAVs), switched to tenofovir alafenamide (TAF) and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and end stage renal disease who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and moderate or severe hepatic impairment who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. |
| Measure Participants | 61 | 13 | 23 |
| Mean (Standard Deviation) [percent change] |
1.293
(4.4136)
|
-0.283
(4.5327)
|
-0.249
(3.9127)
|
| Title | Percentage of Participants Achieving Virologic Response (Plasma HBV DNA < 20 IU/mL) at Week 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 78 | 15 | 31 |
| Number [percentage of participants] |
92.3
118.3%
|
93.3
622%
|
100.0
322.6%
|
| Title | Percentage of Participants Achieving Virologic Response (Plasma HBV DNA < 20 IU/mL) at Week 96 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | Participants with chronic hepatitis B (CHB) and moderate or severe renal impairment who were virologically suppressed and took tenofovir disoproxil fumarate (TDF), a TDF-containing anti-hepatitis B virus (HBV) regimen, or other oral antivirals (OAVs), switched to tenofovir alafenamide (TAF) and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and end stage renal disease who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and moderate or severe hepatic impairment who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. |
| Measure Participants | 78 | 15 | 31 |
| Number [percentage of participants] |
83.3
106.8%
|
86.7
578%
|
77.4
249.7%
|
| Title | Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (≥ Lower Limit of Detection [LLOD]) at Week 24 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 78 | 15 | 31 |
| Number [percentage of participants] |
21.8
27.9%
|
40.0
266.7%
|
22.6
72.9%
|
| Title | Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (≥ LLOD) at Week 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 78 | 15 | 31 |
| Number [percentage of participants] |
26.9
34.5%
|
26.7
178%
|
25.8
83.2%
|
| Title | Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (≥ LLOD) at Week 96 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | Participants with chronic hepatitis B (CHB) and moderate or severe renal impairment who were virologically suppressed and took tenofovir disoproxil fumarate (TDF), a TDF-containing anti-hepatitis B virus (HBV) regimen, or other oral antivirals (OAVs), switched to tenofovir alafenamide (TAF) and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and end stage renal disease who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and moderate or severe hepatic impairment who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. |
| Measure Participants | 78 | 15 | 31 |
| Number [percentage of participants] |
14.1
18.1%
|
20.0
133.3%
|
0
0%
|
| Title | Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 24 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 78 | 15 | 31 |
| Number [percentage of participants] |
75.6
96.9%
|
60.0
400%
|
77.4
249.7%
|
| Title | Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 78 | 15 | 31 |
| Number [percentage of participants] |
65.4
83.8%
|
66.7
444.7%
|
74.2
239.4%
|
| Title | Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 96 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | Participants with chronic hepatitis B (CHB) and moderate or severe renal impairment who were virologically suppressed and took tenofovir disoproxil fumarate (TDF), a TDF-containing anti-hepatitis B virus (HBV) regimen, or other oral antivirals (OAVs), switched to tenofovir alafenamide (TAF) and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and end stage renal disease who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and moderate or severe hepatic impairment who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. |
| Measure Participants | 78 | 15 | 31 |
| Number [percentage of participants] |
69.2
88.7%
|
66.7
444.7%
|
77.4
249.7%
|
| Title | Percentage of Participants With Serological Response: Loss of Hepatitis B s-Antigen (HBsAg) at Week 24 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 78 | 15 | 30 |
| Number [percentage of participants] |
0
0%
|
0
0%
|
0
0%
|
| Title | Percentage of Participants With Serological Response: Loss of HBsAg at Week 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Serologically Evaluable Full Analysis Set for HBsAg Loss/Seroconversion with available data were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 78 | 15 | 30 |
| Number [percentage of participants] |
0.0
0%
|
6.7
44.7%
|
3.3
10.6%
|
| Title | Percentage of Participants With Serological Response: Loss of HBsAg at Week 96 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Serologically Evaluable Full Analysis Set for HBsAg Loss/Seroconversion with available data were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | Participants with chronic hepatitis B (CHB) and moderate or severe renal impairment who were virologically suppressed and took tenofovir disoproxil fumarate (TDF), a TDF-containing anti-hepatitis B virus (HBV) regimen, or other oral antivirals (OAVs), switched to tenofovir alafenamide (TAF) and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and end stage renal disease who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and moderate or severe hepatic impairment who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. |
| Measure Participants | 78 | 15 | 30 |
| Number [percentage of participants] |
0
0%
|
0
0%
|
6.7
21.6%
|
| Title | Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 24 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Serologically Evaluable Full Analysis Set for HBsAg Loss/Seroconversion were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 78 | 15 | 30 |
| Number [percentage of participants] |
0
0%
|
0
0%
|
0
0%
|
| Title | Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Serologically Evaluable Full Analysis Set for HBsAg Loss/Seroconversion were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 78 | 15 | 30 |
| Number [percentage of participants] |
0
0%
|
0
0%
|
0
0%
|
| Title | Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 96 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Serologically Evaluable Full Analysis Set for HBsAg Loss/Seroconversion were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | Participants with chronic hepatitis B (CHB) and moderate or severe renal impairment who were virologically suppressed and took tenofovir disoproxil fumarate (TDF), a TDF-containing anti-hepatitis B virus (HBV) regimen, or other oral antivirals (OAVs), switched to tenofovir alafenamide (TAF) and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and end stage renal disease who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and moderate or severe hepatic impairment who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. |
| Measure Participants | 78 | 15 | 30 |
| Number [percentage of participants] |
0
0%
|
0
0%
|
0
0%
|
| Title | Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 24 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 13 | 3 | 3 |
| Number [percentage of participants] |
0
0%
|
0
0%
|
0
0%
|
| Title | Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Serologically Evaluable Full Analysis Set were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 13 | 3 | 3 |
| Number [percentage of participants] |
0
0%
|
0
0%
|
0
0%
|
| Title | Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 96 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | Participants with chronic hepatitis B (CHB) and moderate or severe renal impairment who were virologically suppressed and took tenofovir disoproxil fumarate (TDF), a TDF-containing anti-hepatitis B virus (HBV) regimen, or other oral antivirals (OAVs), switched to tenofovir alafenamide (TAF) and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and end stage renal disease who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and moderate or severe hepatic impairment who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. |
| Measure Participants | 13 | 3 | 3 |
| Number [percentage of participants] |
0
0%
|
33.3
222%
|
0
0%
|
| Title | Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 24 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Serologically Evaluable Full Analysis Set for HBeAg Loss/Seroconversion were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 13 | 3 | 3 |
| Number [percentage of participants] |
0
0%
|
0
0%
|
0
0%
|
| Title | Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Serologically Evaluable Full Analysis Set for HBeAg Loss/Seroconversion were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 13 | 3 | 3 |
| Number [percentage of participants] |
0
0%
|
0
0%
|
0
0%
|
| Title | Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 96 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Serologically Evaluable Full Analysis Set for HBeAg Loss/Seroconversion were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | Participants with chronic hepatitis B (CHB) and moderate or severe renal impairment who were virologically suppressed and took tenofovir disoproxil fumarate (TDF), a TDF-containing anti-hepatitis B virus (HBV) regimen, or other oral antivirals (OAVs), switched to tenofovir alafenamide (TAF) and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and end stage renal disease who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and moderate or severe hepatic impairment who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. |
| Measure Participants | 13 | 3 | 3 |
| Number [percentage of participants] |
0
0%
|
33.3
222%
|
0
0%
|
| Title | 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 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 78 | 15 | 31 |
| ALT by central laboratory |
92.3
118.3%
|
93.3
622%
|
83.9
270.6%
|
| ALT by AASLD criteria |
87.2
111.8%
|
93.3
622%
|
80.6
260%
|
| Title | Percentage of Participants With Normal ALT at Week 48 by Central Laboratory and the AASLD Criteria |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 78 | 15 | 31 |
| ALT by central laboratory |
89.7
115%
|
86.7
578%
|
90.3
291.3%
|
| ALT by AASLD criteria |
87.2
111.8%
|
80.0
533.3%
|
80.6
260%
|
| Title | Percentage of Participants With Normal ALT at Week 96 by Central Laboratory and the AASLD Criteria |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | Participants with chronic hepatitis B (CHB) and moderate or severe renal impairment who were virologically suppressed and took tenofovir disoproxil fumarate (TDF), a TDF-containing anti-hepatitis B virus (HBV) regimen, or other oral antivirals (OAVs), switched to tenofovir alafenamide (TAF) and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and end stage renal disease who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and moderate or severe hepatic impairment who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. |
| Measure Participants | 78 | 15 | 31 |
| ALT by central laboratory |
82.1
105.3%
|
86.7
578%
|
71.0
229%
|
| ALT by AASLD criteria |
74.4
95.4%
|
86.7
578%
|
58.1
187.4%
|
| Title | Percentage of Participants With Normalized ALT at Week 24 by Central Laboratory and the AASLD Criteria |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set with Baseline ALT > ULN were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 5 | 0 | 10 |
| Normalized ALT by Central Laboratory |
66.7
85.5%
|
50.0
333.3%
|
|
| Normalized ALT by AASLD Criteria |
40.0
51.3%
|
60.0
400%
|
| Title | Percentage of Participants With Normalized ALT at Week 48 by Central Laboratory and the AASLD Criteria |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set with Baseline ALT > ULN were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 5 | 0 | 10 |
| Normalized ALT by Central Laboratory |
33.3
42.7%
|
75.0
500%
|
|
| Normalized ALT by AASLD Criteria |
60.0
76.9%
|
60.0
400%
|
| Title | Percentage of Participants With Normalized ALT at Week 96 by Central Laboratory and the AASLD Criteria |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set with Baseline ALT > ULN were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | Participants with chronic hepatitis B (CHB) and moderate or severe renal impairment who were virologically suppressed and took tenofovir disoproxil fumarate (TDF), a TDF-containing anti-hepatitis B virus (HBV) regimen, or other oral antivirals (OAVs), switched to tenofovir alafenamide (TAF) and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and end stage renal disease who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and moderate or severe hepatic impairment who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. |
| Measure Participants | 5 | 0 | 10 |
| Normalized ALT by Central Laboratory |
33.3
42.7%
|
50.0
333.3%
|
|
| Normalized ALT by AASLD Criteria |
20.0
25.6%
|
50.0
333.3%
|
| Title | Change From Baseline in FibroTest® Score at Week 24 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set with available data were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 74 | 15 | 31 |
| Mean (Standard Deviation) [units on a scale] |
-0.01
(0.099)
|
-0.01
(0.064)
|
-0.05
(0.106)
|
| Title | Change From Baseline in FibroTest® Score at Week 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set with available data were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 73 | 14 | 31 |
| Mean (Standard Deviation) [units on a scale] |
-0.03
(0.102)
|
-0.01
(0.071)
|
-0.03
(0.102)
|
| Title | Change From Baseline in FibroTest® Score at Week 96 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set with available data were analyzed. |
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease | Part B: Hepatic Impairment |
|---|---|---|---|
| Arm/Group Description | Participants with chronic hepatitis B (CHB) and moderate or severe renal impairment who were virologically suppressed and took tenofovir disoproxil fumarate (TDF), a TDF-containing anti-hepatitis B virus (HBV) regimen, or other oral antivirals (OAVs), switched to tenofovir alafenamide (TAF) and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and end stage renal disease who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. | Participants with CHB and moderate or severe hepatic impairment who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. |
| Measure Participants | 65 | 13 | 26 |
| Mean (Standard Deviation) [units on a scale] |
-0.01
(0.114)
|
0.03
(0.107)
|
-0.02
(0.118)
|
| Title | Change From Baseline in Child-Pugh-Turcotte (CPT) Score in Hepatically Impaired Participants at Week 24 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set only from Part B (Hepatic Impairment) were analyzed. |
| Arm/Group Title | Part B: Hepatic Impairment |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 31 |
| Mean (Standard Deviation) [units on a scale] |
0
(1.1)
|
| Title | Change From Baseline in CPT Score in Hepatically Impaired Participants at Week 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set only from Part B (Hepatic Impairment) were analyzed. |
| Arm/Group Title | Part B: Hepatic Impairment |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 31 |
| Mean (Standard Deviation) [units on a scale] |
0
(1.1)
|
| Title | Change From Baseline in CPT Score in Hepatically Impaired Participants at Week 96 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set only from Part B (Hepatic Impairment) with available data were analyzed. |
| Arm/Group Title | Part B: Hepatic Impairment |
|---|---|
| Arm/Group Description | Participants with CHB and moderate or severe hepatic impairment who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. |
| Measure Participants | 25 |
| Mean (Standard Deviation) [units on a scale] |
0
(1.2)
|
| Title | Change From Baseline in Model for End-Stage Liver Disease (MELD) Score in Hepatically Impaired Participants at Week 24 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set only from Part B (Hepatic Impairment) were analyzed. |
| Arm/Group Title | Part B: Hepatic Impairment |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 31 |
| Mean (Standard Deviation) [units on a scale] |
-0.6
(1.94)
|
| Title | Change From Baseline in MELD Score in Hepatically Impaired Participants at Week 48 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set only from Part B (Hepatic Impairment) with available data were analyzed. |
| Arm/Group Title | Part B: Hepatic Impairment |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 30 |
| Mean (Standard Deviation) [units on a scale] |
0.1
(2.35)
|
| Title | Change From Baseline in MELD Score in Hepatically Impaired Participants at Week 96 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set only from Part B (Hepatic Impairment) with available data were analyzed. |
| Arm/Group Title | Part B: Hepatic Impairment |
|---|---|
| Arm/Group Description | Participants with CHB and moderate or severe hepatic impairment who were virologically suppressed and took TDF, a TDF-containing anti-HBV regimen, or OAVs, switched to TAF and received TAF 25 mg tablet once daily orally for 96 weeks. |
| Measure Participants | 25 |
| Mean (Standard Deviation) [units on a scale] |
-1.0
(1.61)
|
Adverse Events
| Time Frame | Adverse Events: From the first dose date up to last dose date (maximum: 108.1 weeks) plus 3 days; All-Cause Mortality: Enrollment up to last dose date (maximum: 166.2 weeks) plus 3 days | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Adverse Events: The Safety Analysis Set included all participants who were enrolled and received at least 1 dose of study drug. All-Cause Mortality: The Full Analysis Set included all participants who were enrolled and received at least one dose of study drug. | |||||
| Arm/Group Title | Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease (Cohort 2) | Part B (Hepatic Impairment): Moderate or Severe Hepatic Impair | |||
| Arm/Group Description | 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. | 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. | 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. | |||
All Cause Mortality |
||||||
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease (Cohort 2) | Part B (Hepatic Impairment): Moderate or Severe Hepatic Impair | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/78 (2.6%) | 1/15 (6.7%) | 2/31 (6.5%) | |||
Serious Adverse Events |
||||||
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease (Cohort 2) | Part B (Hepatic Impairment): Moderate or Severe Hepatic Impair | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 12/78 (15.4%) | 8/15 (53.3%) | 10/31 (32.3%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Thrombocytopenia | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Cardiac disorders | ||||||
| Atrial flutter | 0/78 (0%) | 0/15 (0%) | 1/31 (3.2%) | |||
| Atrioventricular block complete | 1/78 (1.3%) | 0/15 (0%) | 0/31 (0%) | |||
| Ear and labyrinth disorders | ||||||
| Deafness neurosensory | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Endocrine disorders | ||||||
| Adrenal mass | 0/78 (0%) | 0/15 (0%) | 1/31 (3.2%) | |||
| Eye disorders | ||||||
| Cataract | 2/78 (2.6%) | 0/15 (0%) | 0/31 (0%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal pain | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Ascites | 0/78 (0%) | 0/15 (0%) | 1/31 (3.2%) | |||
| Colitis | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Duodenal ulcer haemorrhage | 0/78 (0%) | 0/15 (0%) | 1/31 (3.2%) | |||
| Gingival bleeding | 0/78 (0%) | 0/15 (0%) | 1/31 (3.2%) | |||
| Intestinal obstruction | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Upper gastrointestinal haemorrhage | 0/78 (0%) | 0/15 (0%) | 1/31 (3.2%) | |||
| General disorders | ||||||
| Catheter site discharge | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Hepatobiliary disorders | ||||||
| Bile duct stone | 0/78 (0%) | 0/15 (0%) | 1/31 (3.2%) | |||
| Hepatic failure | 0/78 (0%) | 0/15 (0%) | 1/31 (3.2%) | |||
| Hepatorenal syndrome | 0/78 (0%) | 0/15 (0%) | 1/31 (3.2%) | |||
| Infections and infestations | ||||||
| Bacteraemia | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Fungal cystitis | 0/78 (0%) | 0/15 (0%) | 1/31 (3.2%) | |||
| Lower respiratory tract infection | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Lower respiratory tract infection viral | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Peritonitis bacterial | 0/78 (0%) | 0/15 (0%) | 1/31 (3.2%) | |||
| Pneumonia | 2/78 (2.6%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Sepsis | 0/78 (0%) | 1/15 (6.7%) | 1/31 (3.2%) | |||
| Urinary tract infection | 0/78 (0%) | 0/15 (0%) | 1/31 (3.2%) | |||
| Injury, poisoning and procedural complications | ||||||
| Arteriovenous fistula site complication | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Arteriovenous fistula thrombosis | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Drain site complication | 0/78 (0%) | 0/15 (0%) | 1/31 (3.2%) | |||
| Head injury | 1/78 (1.3%) | 0/15 (0%) | 0/31 (0%) | |||
| Shunt occlusion | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Subdural haematoma | 0/78 (0%) | 0/15 (0%) | 1/31 (3.2%) | |||
| Investigations | ||||||
| Carcinoembryonic antigen increased | 1/78 (1.3%) | 0/15 (0%) | 0/31 (0%) | |||
| Model for end stage liver disease score increased | 0/78 (0%) | 0/15 (0%) | 1/31 (3.2%) | |||
| Metabolism and nutrition disorders | ||||||
| Hyperkalaemia | 1/78 (1.3%) | 0/15 (0%) | 0/31 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 1/78 (1.3%) | 0/15 (0%) | 0/31 (0%) | |||
| Focal myositis | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Bladder cancer | 1/78 (1.3%) | 0/15 (0%) | 0/31 (0%) | |||
| Hepatocellular carcinoma | 0/78 (0%) | 1/15 (6.7%) | 1/31 (3.2%) | |||
| Lung neoplasm malignant | 1/78 (1.3%) | 0/15 (0%) | 0/31 (0%) | |||
| Ovarian cancer | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Rectal cancer | 1/78 (1.3%) | 0/15 (0%) | 0/31 (0%) | |||
| Nervous system disorders | ||||||
| Encephalopathy | 0/78 (0%) | 0/15 (0%) | 1/31 (3.2%) | |||
| Hepatic encephalopathy | 0/78 (0%) | 0/15 (0%) | 2/31 (6.5%) | |||
| Ischaemic stroke | 2/78 (2.6%) | 0/15 (0%) | 1/31 (3.2%) | |||
| Subarachnoid haemorrhage | 1/78 (1.3%) | 0/15 (0%) | 1/31 (3.2%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Bronchospasm | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Dyspnoea | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Haemothorax | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Pleural effusion | 0/78 (0%) | 2/15 (13.3%) | 0/31 (0%) | |||
| Pneumonia aspiration | 1/78 (1.3%) | 0/15 (0%) | 1/31 (3.2%) | |||
| Respiratory failure | 1/78 (1.3%) | 0/15 (0%) | 0/31 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Part A (Renal Impairment): Moderate or Severe Renal Impairment | Part A (Renal Impairment): End Stage Renal Disease (Cohort 2) | Part B (Hepatic Impairment): Moderate or Severe Hepatic Impair | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 34/78 (43.6%) | 15/15 (100%) | 23/31 (74.2%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 2/78 (2.6%) | 3/15 (20%) | 1/31 (3.2%) | |||
| Blood loss anaemia | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Coagulopathy | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Thrombocytopenia | 0/78 (0%) | 1/15 (6.7%) | 1/31 (3.2%) | |||
| Thrombotic thrombocytopenic purpura | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Ear and labyrinth disorders | ||||||
| Deafness neurosensory | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Ear haemorrhage | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Ear pain | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Vertigo | 1/78 (1.3%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Eye disorders | ||||||
| Cataract | 1/78 (1.3%) | 1/15 (6.7%) | 1/31 (3.2%) | |||
| Cataract nuclear | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Conjunctival haemorrhage | 0/78 (0%) | 1/15 (6.7%) | 1/31 (3.2%) | |||
| Iridocyclitis | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal pain | 2/78 (2.6%) | 1/15 (6.7%) | 2/31 (6.5%) | |||
| Abdominal pain lower | 1/78 (1.3%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Ascites | 0/78 (0%) | 2/15 (13.3%) | 4/31 (12.9%) | |||
| Constipation | 2/78 (2.6%) | 4/15 (26.7%) | 3/31 (9.7%) | |||
| Dental caries | 0/78 (0%) | 1/15 (6.7%) | 2/31 (6.5%) | |||
| Diarrhoea | 3/78 (3.8%) | 3/15 (20%) | 6/31 (19.4%) | |||
| Flatulence | 0/78 (0%) | 0/15 (0%) | 2/31 (6.5%) | |||
| Haemorrhoids | 2/78 (2.6%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Mouth ulceration | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Nausea | 1/78 (1.3%) | 1/15 (6.7%) | 1/31 (3.2%) | |||
| Peptic ulcer | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Portal hypertensive gastropathy | 0/78 (0%) | 0/15 (0%) | 2/31 (6.5%) | |||
| Stomatitis | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Toothache | 3/78 (3.8%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Vomiting | 0/78 (0%) | 1/15 (6.7%) | 2/31 (6.5%) | |||
| General disorders | ||||||
| Chest discomfort | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Fatigue | 0/78 (0%) | 0/15 (0%) | 2/31 (6.5%) | |||
| Oedema peripheral | 1/78 (1.3%) | 1/15 (6.7%) | 2/31 (6.5%) | |||
| Pain | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Pyrexia | 0/78 (0%) | 3/15 (20%) | 5/31 (16.1%) | |||
| Hepatobiliary disorders | ||||||
| Jaundice | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Infections and infestations | ||||||
| Cellulitis | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Conjunctivitis | 0/78 (0%) | 1/15 (6.7%) | 2/31 (6.5%) | |||
| Endophthalmitis | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Hordeolum | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Nasopharyngitis | 6/78 (7.7%) | 0/15 (0%) | 0/31 (0%) | |||
| Pneumonia | 2/78 (2.6%) | 1/15 (6.7%) | 1/31 (3.2%) | |||
| Skin infection | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Upper respiratory tract infection | 11/78 (14.1%) | 3/15 (20%) | 6/31 (19.4%) | |||
| Urinary tract infection | 3/78 (3.8%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Arteriovenous fistula site complication | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Incision site pain | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Ligament sprain | 1/78 (1.3%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Limb injury | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Procedural pain | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Shunt occlusion | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Vascular pseudoaneurysm | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Investigations | ||||||
| Blood bilirubin increased | 0/78 (0%) | 0/15 (0%) | 2/31 (6.5%) | |||
| Blood creatinine increased | 1/78 (1.3%) | 0/15 (0%) | 2/31 (6.5%) | |||
| Bone density decreased | 1/78 (1.3%) | 0/15 (0%) | 5/31 (16.1%) | |||
| Metabolism and nutrition disorders | ||||||
| Hyperkalaemia | 1/78 (1.3%) | 2/15 (13.3%) | 0/31 (0%) | |||
| Hyperlipidaemia | 1/78 (1.3%) | 0/15 (0%) | 2/31 (6.5%) | |||
| Hypokalaemia | 0/78 (0%) | 1/15 (6.7%) | 1/31 (3.2%) | |||
| Metabolic acidosis | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Vitamin B12 deficiency | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 0/78 (0%) | 2/15 (13.3%) | 3/31 (9.7%) | |||
| Back pain | 2/78 (2.6%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Bone loss | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Groin pain | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Musculoskeletal pain | 1/78 (1.3%) | 3/15 (20%) | 1/31 (3.2%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Hepatocellular carcinoma | 1/78 (1.3%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Ovarian cancer stage I | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Nervous system disorders | ||||||
| Amnesia | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Carotid arteriosclerosis | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Cerebral atrophy | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Cerebrovascular accident | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Cognitive disorder | 1/78 (1.3%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Dementia | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Dizziness | 3/78 (3.8%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Dyskinesia | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Headache | 2/78 (2.6%) | 0/15 (0%) | 2/31 (6.5%) | |||
| Hydrocephalus | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Vascular encephalopathy | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Psychiatric disorders | ||||||
| Insomnia | 4/78 (5.1%) | 1/15 (6.7%) | 2/31 (6.5%) | |||
| Renal and urinary disorders | ||||||
| Chronic kidney disease | 0/78 (0%) | 0/15 (0%) | 2/31 (6.5%) | |||
| Haematuria | 3/78 (3.8%) | 1/15 (6.7%) | 1/31 (3.2%) | |||
| Renal mass | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 4/78 (5.1%) | 0/15 (0%) | 6/31 (19.4%) | |||
| Dyspnoea | 1/78 (1.3%) | 2/15 (13.3%) | 0/31 (0%) | |||
| Haemoptysis | 0/78 (0%) | 1/15 (6.7%) | 1/31 (3.2%) | |||
| Nasal congestion | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Nasal obstruction | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Oropharyngeal pain | 1/78 (1.3%) | 0/15 (0%) | 3/31 (9.7%) | |||
| Pleural effusion | 0/78 (0%) | 3/15 (20%) | 2/31 (6.5%) | |||
| Productive cough | 0/78 (0%) | 2/15 (13.3%) | 1/31 (3.2%) | |||
| Pulmonary oedema | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Rhinorrhoea | 1/78 (1.3%) | 2/15 (13.3%) | 0/31 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Dermatitis | 1/78 (1.3%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Pruritus | 3/78 (3.8%) | 2/15 (13.3%) | 1/31 (3.2%) | |||
| Skin lesion | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Vascular disorders | ||||||
| Hypertension | 2/78 (2.6%) | 4/15 (26.7%) | 1/31 (3.2%) | |||
| Hypotension | 0/78 (0%) | 2/15 (13.3%) | 0/31 (0%) | |||
| Thrombosis | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
| Venous occlusion | 0/78 (0%) | 1/15 (6.7%) | 0/31 (0%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years
Results Point of Contact
| Name/Title | Gilead Clinical Study Information Center |
|---|---|
| Organization | Gilead Sciences |
| Phone | 1-833-445-3230 (GILEAD-0) |
| GileadClinicalTrials@gilead.com |
Responsible Party:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT03180619
Other Study ID Numbers:
- GS-US-320-4035
- 2016-004625-16
First Posted:
Jun 8, 2017
Last Update Posted:
Sep 27, 2021
Last Verified:
Aug 1, 2021