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)

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: TAF

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Calgary, Canada, T2N4Z6
    • University of Calgary Liver Unit
  • Montreal, Canada, H2X 0A9
    • Centre de Recherche du Centre Hospitalier de l'Université de Montréal
  • Toronto, Canada, M6H 3M1
    • Toronto Liver Centre
  • Toronto, Canada, M5G 2C4
    • University Health Network,Toronto general Hospital,Toronto centre for liver disease
  • Vancouver, Canada, V6Z 2K5
    • (G.I.R.I.) GI Research Institute
• Hong Kong
  • Kowloon, Hong Kong
    • Princess Margaret Hospital
  • Tai Po, Hong Kong
    • Alice Ho Miu Ling Nethersole Hospital
  • NT
    • Shatin, NT, Hong Kong
      • Prince of Wales Hospital
• Italy
  • Bologna, Italy, 40138
    • Dipartimento di Scienze Mediche e Chirurgiche (DIMEC) AOU Policlinico S.Orsola-Malpighi di Bologna
  • Milan, Italy, 20122
    • UOC Gastroenterol-Epatol.-Fondazione IRCCS Ca Granda
  • Milan
    • Rozzano, Milan, Italy, 20089
      • U.O. Medicina Generale Epatologia IRCCS Humanitas Centro di Ricerca Traslazionale in Epatologia
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Pusan National University Hospital
  • Busan, Korea, Republic of, 49201
    • Dong-A University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 120-752
    • Yonsei University Health system, Severance Hospital
• New Zealand
  • Auckland
    • Grafton, Auckland, New Zealand, 1010
      • Auckland Clinical Studies
• Taiwan
  • Changhua, Taiwan, 500
    • Changhua Christian Hospital
  • Chiayi City, Taiwan, 60002
    • Ditmanson Medical Foundation Chia-Yi Christian Hospital
  • Kaohsiung, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Kaohsiung City, Taiwan, 83301
    • Kaohsiung Chang Gung Memorial Hospital
  • Taichung, Taiwan, 40705
    • Taichung Veterans Genl Hosp
  • Taipei, Taiwan, 10001
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11217
    • Veterans General Hospital-Taipei
  • Taoyuan City, Taiwan, 333
    • Chang Gung Medical Foundation, Linkou Chang Gung Memorial Hospital
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • King's College Hospital NHS Foundation Trust
  • London, United Kingdom, NG7 2UH
    • Nottingham University Hospital
• United States
  • California
    • Los Angeles, California, United States, 90020
      • Coalition of Inclusive Medicine
    • San Jose, California, United States, 95128
      • Silicon Valley Research Institute, Inc
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Washington
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / 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: Vemlidy®
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: Vemlidy®
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: Vemlidy®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Virologic Response (Plasma Hepatitis B Virus [HBV] Deoxyribonucleic Acid [DNA] < 20 IU/mL) at Week 24	The percentage of participants with HBV DNA < 20 IU/mL at Week 24 was determined by the Missing = Failure (M = F) approach.	Week 24
Percentage of Participants Who Experienced Graded Treatment-Emergent Adverse Events (AEs) at Week 24	Treatment-emergent AEs were defined as: Any AEs with an onset date on or after the study drug start date and no later than the study drug stop date + 3 days after permanent discontinuation of study drug;; Any AEs with onset date on or after the study drug start date for those who have not permanently discontinued study drug;; Any AEs leading to premature discontinuation of study drug. The most severe graded AE from all tests was counted for each participant.	Week 24
Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 24	Graded treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any postbaseline visit, up to and including the date of last dose of study drug + 3 days for participants who permanently discontinued study drug or the last available date in the database snapshot for participants who were on treatment at the time of the analysis. The most severe graded abnormality from all tests was counted for each participant.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 48	Treatment-emergent AEs were defined as: Any AEs with an onset date on or after the study drug start date and no later than the study drug stop date + 3 days after permanent discontinuation of study drug; Any AEs with onset date on or after the study drug start date for those who have not permanently discontinued study drug; Any AEs leading to premature discontinuation of study drug. The most severe graded AE from all tests was counted for each participant.	Week 48
Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 96	Treatment-emergent AEs were defined as: Any AEs with an onset date on or after the study drug start date and no later than the study drug stop date + 3 days after permanent discontinuation of study drug; Any AEs with onset date on or after the study drug start date for those who have not permanently discontinued study drug; Any AEs leading to premature discontinuation of study drug. The most severe graded AE from all tests was counted for each participant.	Week 96
Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 48	Graded treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any postbaseline visit, up to and including the date of last dose of study drug + 3 days for participants who permanently discontinued study drug or the last available date in the database snapshot for participants who were on treatment at the time of the analysis. The most severe graded abnormality from all tests was counted for each participant.	Week 48
Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 96	Graded treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any post-baseline visit, up to and including the date of last dose of study drug + 3 days for participants who permanently discontinued study drug or the last available date in the database snapshot for participants who were on treatment at the time of the analysis. The most severe graded abnormality from all tests was counted for each participant.	Week 96
Change From Baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFRcg) in Participants With Moderate or Severe Renal Impairment and Hepatically Impaired Participants at Week 24	GFR is a measure of the rate at which blood is filtered by the kidney. Cockcroft-Gault is an equation (calculation) used to estimate GFR based on serum creatinine, weight, and gender. eGFRcg = (140 - age in years) x (body weight in kg) x (0.85 if female) divided by 72 x serum creatinine in mg/dL. Moderate renal impairment= 30 mL/min ≤ eGFRCG ≤ 59 mL/min Severe renal impairment= 15 mL/min ≤ eGFRCG < 30 mL/min Change from baseline was calculated as the value at Week 24 minus the value at Baseline.	Baseline, Week 24
Change From Baseline in eGFRcg in Participants With Moderate or Severe Renal Impairment and Hepatically Impaired Participants at Week 48	GFR is a measure of the rate at which blood is filtered by the kidney. Cockcroft-Gault is an equation (calculation) used to estimate GFR based on serum creatinine, weight, and gender. eGFRcg = (140 - age in years) x (body weight in kg) x (0.85 if female) divided by 72 x serum creatinine in mg/dL. Moderate renal impairment= 30 mL/min ≤ eGFRCG ≤ 59 mL/min Severe renal impairment= 15 mL/min ≤ eGFRCG < 30 mL/min Change from baseline was calculated as the value at Week 48 minus the value at Baseline.	Baseline, Week 48
Change From Baseline in eGFRcg in Participants With Moderate or Severe Renal Impairment and Hepatically Impaired Participants at Week 96	GFR is a measure of the rate at which blood is filtered by the kidney. Cockcroft-Gault is an equation (calculation) used to estimate GFR based on serum creatinine, weight, and gender. eGFRcg = (140 - age in years) x (body weight in kg) x (0.85 if female) divided by 72 x serum creatinine in mg/dL. Moderate renal impairment= 30 mL/min ≤ eGFRCG ≤ 59 mL/min Severe renal impairment= 15 mL/min ≤ eGFRCG < 30 mL/min Change from baseline was calculated as the value at Week 96 minus the value at Baseline.	Baseline, Week 96
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 24	Percent change = Change from baseline at a postbaseline visit/baseline * 100%.	Baseline, Week 24
Percent Change From Baseline in Hip BMD at Week 48	Percent change = Change from baseline at a postbaseline visit/baseline * 100%.	Baseline, Week 48
Percent Change From Baseline in Hip BMD at Week 96	Percent change = Change from baseline at a postbaseline visit/baseline * 100%.	Baseline, Week 96
Percent Change From Baseline in Spine BMD at Week 24	Percent change = Change from baseline at a postbaseline visit/baseline * 100%.	Baseline, Week 24
Percent Change From Baseline in Spine BMD at Week 48	Percent change = Change from baseline at a postbaseline visit/baseline * 100%.	Baseline, Week 48
Percent Change From Baseline in Spine BMD at Week 96	Percent change = Change from baseline at a postbaseline visit/baseline * 100%.	Baseline, Week 96
Percentage of Participants Achieving Virologic Response (Plasma HBV DNA < 20 IU/mL) at Week 48	The percentage of participants with HBV DNA < 20 IU/mL at Week 48 was determined by the Missing = Failure (M = F) approach.	Weeks 48
Percentage of Participants Achieving Virologic Response (Plasma HBV DNA < 20 IU/mL) at Week 96	The percentage of participants with HBV DNA < 20 IU/mL at Week 48 was determined by the Missing = Failure (M = F) approach.	Weeks 96
Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (≥ Lower Limit of Detection [LLOD]) at Week 24	The percentage of participants with HBV DNA < 20 IU/mL and target detected (≥ LLOD; i.e. 10 IU/mL) at Week 24 was determined by the M = F approach.	Week 24
Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (≥ LLOD) at Week 48	The percentage of participants with HBV DNA < 20 IU/mL and target detected (≥ LLOD; i.e. 10 IU/mL) at Week 48 was determined by the M = F approach.	Week 48
Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (≥ LLOD) at Week 96	The percentage of participants with HBV DNA < 20 IU/mL and target detected (≥ LLOD; i.e. 10 IU/mL) at Week 96 was determined by the M = F approach.	Week 96
Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 24	The percentage of participants with HBV DNA < 20 IU/mL and target not detected (< LLOD; i.e. 10 IU/mL) at Week 24 was determined by the M = F approach.	Week 24
Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 48	The percentage of participants with HBV DNA < 20 IU/mL and target not detected (< LLOD; i.e. 10 IU/mL) at Week 48 was determined by the M = F approach.	Weeks 48
Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 96	The percentage of participants with HBV DNA < 20 IU/mL and target not detected (< LLOD; i.e. 10 IU/mL) at Week 96 was determined by the M = F approach.	Weeks 96
Percentage of Participants With Serological Response: Loss of Hepatitis B s-Antigen (HBsAg) at Week 24	HBsAg loss was defined as HBsAg changing from positive at baseline to negative at a postbaseline. The M = F approach was used for this analysis.	Week 24
Percentage of Participants With Serological Response: Loss of HBsAg at Week 48	HBsAg loss was defined as HBsAg changing from positive at baseline to negative at a postbaseline. The M = F approach was used for this analysis.	Week 48
Percentage of Participants With Serological Response: Loss of HBsAg at Week 96	HBsAg loss was defined as HBsAg changing from positive at baseline to negative at a postbaseline. The M = F approach was used for this analysis.	Week 96
Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 24	HBsAg seroconversion was defined as HBsAg loss and HBsAb test changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.	Week 24
Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 48	HBsAg seroconversion was defined as HBsAg loss and HBsAb test changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.	Week 48
Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 96	HBsAg seroconversion was defined as HBsAg loss and HBsAb test changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.	Week 96
Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 24	HBeAg loss was defined as HBeAg changing from positive at baseline to negative at a postbaseline. The M = F approach was used for this analysis.	Week 24
Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 48	HBeAg loss was defined as HBeAg changing from positive at baseline to negative at a postbaseline. The M = F approach was used for this analysis.	Week 48
Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 96	HBeAg loss was defined as HBeAg changing from positive at baseline to negative at a postbaseline. The M = F approach was used for this analysis.	Week 96
Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 24	HBeAg seroconversion was defined as HBeAg loss and HBeAb test changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.	Week 24
Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 48	HBeAg seroconversion was defined as HBeAg loss and HBeAb test changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.	Week 48
Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 96	HBeAg seroconversion was defined as HBeAg loss and HBeAb test changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.	Week 96
Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Week 24 by Central Laboratory and the American Association for the Study of Liver Diseases (AASLD) Criteria	Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to < 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to < 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. The M = F approach was used for this analysis.	Week 24
Percentage of Participants With Normal ALT at Week 48 by Central Laboratory and the AASLD Criteria	Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to < 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to < 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. The M = F approach was used for this analysis.	Week 48
Percentage of Participants With Normal ALT at Week 96 by Central Laboratory and the AASLD Criteria	Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to < 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to < 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. The M = F approach was used for this analysis.	Week 96
Percentage of Participants With Normalized ALT at Week 24 by Central Laboratory and the AASLD Criteria	ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit. Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to < 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to < 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. The M = F approach was used for this analysis.	Week 24
Percentage of Participants With Normalized ALT at Week 48 by Central Laboratory and the AASLD Criteria	ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit. Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to < 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to < 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. The M = F approach was used for this analysis.	Week 48
Percentage of Participants With Normalized ALT at Week 96 by Central Laboratory and the AASLD Criteria	ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit. Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to < 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to < 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. The M = F approach was used for this analysis.	Week 96
Change From Baseline in FibroTest® Score at Week 24	The FibroTest® score is used to assess liver fibrosis. Scores range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis. Change from baseline was calculated as the value at Week 24 minus the value at Baseline.	Baseline, Week 24
Change From Baseline in FibroTest® Score at Week 48	The FibroTest® score is used to assess liver fibrosis. Scores range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis. Change from baseline was calculated as the value at Week 48 minus the value at Baseline.	Baseline, Week 48
Change From Baseline in FibroTest® Score at Week 96	The FibroTest® score is used to assess liver fibrosis. Scores range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis. Change from baseline was calculated as the value at Week 96 minus the value at Baseline.	Week 96
Change From Baseline in Child-Pugh-Turcotte (CPT) Score in Hepatically Impaired Participants at Week 24	CPT scores grade the severity of cirrhosis and are used to determine the need for liver transplantation. Scores can range from 5 to 15, with higher scores indicating a greater severity of disease.	Baseline, Week 24
Change From Baseline in CPT Score in Hepatically Impaired Participants at Week 48	CPT scores grade the severity of cirrhosis and are used to determine the need for liver transplantation. Scores can range from 5 to 15, with higher scores indicating a greater severity of disease.	Baseline, Week 48
Change From Baseline in CPT Score in Hepatically Impaired Participants at Week 96	CPT scores grade the severity of cirrhosis and are used to determine the need for liver transplantation. Scores can range from 5 to 15, with higher scores indicating a greater severity of disease.	Baseline, Week 96
Change From Baseline in Model for End-Stage Liver Disease (MELD) Score in Hepatically Impaired Participants at Week 24	MELD scores are used to assess prognosis and suitability for liver transplantation. Scores can range from 6 to 40, with higher scores indicating greater disease severity.	Baseline, Week 24
Change From Baseline in MELD Score in Hepatically Impaired Participants at Week 48	MELD scores are used to assess prognosis and suitability for liver transplantation. Scores can range from 6 to 40, with higher scores indicating greater disease severity.	Baseline, Week 48
Change From Baseline in MELD Score in Hepatically Impaired Participants at Week 96	MELD scores are used to assess prognosis and suitability for liver transplantation. Scores can range from 6 to 40, with higher scores indicating greater disease severity.	Baseline, Week 96

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Lim YS, Lin CY, Heo J, Bae H, Chuang WL, Hui AJ, et al. Safety and Efficacy of Switching to Tenofovir Alafenamide in Virally Suppressed Chronic Hepatitis B Patients With Hepatic Impairment: Week-48 Results From a Phase 2 Open-label Study [Poster SAT442]. The Digital International Liver Congress (ILC); 2020 27-29 August.
• Janssen HLA, Lampertico P, Chen CY, Heo J, Fournier C, Ahn SH, et al. Safety and Efficacy of Switching to Tenofovir Alafenamide in Virally Suppressed Chronic Hepatitis B Patients With Renal Impairment: Week-48 Results From a Phase 2 Open-label Study [Poster SAT429]. The Digital International Liver Congress (ILC); 2020 27-29 August.
• Lim YS, Lampertico P, Bae H, Chuang WL, Heo J, Huang YH, et al. Switching From Tenofovir Disoproxil Fumarate or Other Oral Antiviral Therapy to Tenofovir Alafenamide in Virally Suppressed Chronic Hepatitis B Patients With Hepatic Impairment: Week 24 Efficacy and Safety Results From a Phase 2 Open-label Study [Poster 501]. AASLD: The Liver Meeting; 2019 08-12 November; Boston, MA.
• Janssen HLA, Lim YS, Gane EJ, Fournier C, Ahn SH, Tsang O, et al. Efficacy and Safety of Switching to Tenofovir Alafenamide in Virally Suppressed Chronic Hepatitis B Patients With Renal Impairment: Week 24 Results From a Phase 2 Open-label Study [Poster 483]. AASLD: The Liver Meeting; 2019 08-12 November; Boston, MA.

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2017
• Primary Completion (Actual): March 27, 2019
• Study Completion (Actual): September 4, 2020

Study Registration Dates

• First Submitted: June 6, 2017
• First Submitted That Met QC Criteria: June 6, 2017
• First Posted (Actual): June 8, 2017

Study Record Updates

• Last Update Posted (Actual): September 27, 2021
• Last Update Submitted That Met QC Criteria: August 30, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis B; Hepatitis; Hepatitis B, Chronic; Hepatitis, Chronic
• Other Study ID Numbers: GS-US-320-4035; 2016-004625-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy
• IPD Sharing Time Frame: 18 months after study completion
• IPD Sharing Access Criteria: A secured external environment with username, password, and RSA code.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No