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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)

Primary Purpose

Chronic Hepatitis B

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

TAF

About this trial

This is an interventional treatment trial for Chronic Hepatitis B

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Coalition of Inclusive Medicine
Silicon Valley Research Institute, Inc
Henry Ford Health System
Harborview Medical Center
University of Calgary Liver Unit
Centre de Recherche du Centre Hospitalier de l'Universite de Montreal
University Health Network,Toronto general Hospital,Toronto centre for liver disease
Toronto Liver Centre
(G.I.R.I.) GI Research Institute
Prince of Wales Hospital
Princess Margaret Hospital
Alice Ho Miu Ling Nethersole Hospital
U.O. Medicina Generale Epatologia IRCCS Humanitas Centro di Ricerca Traslazionale in Epatologia
Dipartimento di Scienze Mediche e Chirurgiche (DIMEC) AOU Policlinico S.Orsola-Malpighi di Bologna
UOC Gastroenterol-Epatol.-Fondazione IRCCS Ca Granda
Dong-A University Hospital
Pusan National University Hospital
Asan Medical Center
Yonsei University Health System, Severance Hospital
Auckland Clinical Studies
Changhua Christian Hospital
Ditmanson Medical Foundation Chia-Yi Christian Hospital
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung Medical University Chung-Ho Memorial Hospital
Taichung Veterans Genl Hosp
National Taiwan University Hospital
Veterans General Hospital-Taipei
Chang Gung Medical Foundation, Linkou Chang Gung Memorial Hospital
Nottingham University Hospital
King's College Hospital NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Part A (Renal Impairment): Moderate or Severe Renal Impairment

Part A (Renal Impairment): End Stage Renal Disease

Part B: Hepatic Impairment

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

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.

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.

Secondary Outcome Measures

Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 48

Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 96

Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at 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.

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.

Change From Baseline in eGFRcg in Participants With Moderate or Severe Renal Impairment and Hepatically Impaired Participants at Week 48

Change From Baseline in eGFRcg in Participants With Moderate or Severe Renal Impairment and Hepatically Impaired Participants at 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%.

Percent Change From Baseline in Hip BMD at Week 48

Percent change = Change from baseline at a postbaseline visit/baseline * 100%.

Percent Change From Baseline in Hip BMD at Week 96

Percent change = Change from baseline at a postbaseline visit/baseline * 100%.

Percent Change From Baseline in Spine BMD at Week 24

Percent change = Change from baseline at a postbaseline visit/baseline * 100%.

Percent Change From Baseline in Spine BMD at Week 48

Percent change = Change from baseline at a postbaseline visit/baseline * 100%.

Percent Change From Baseline in Spine BMD at 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Percentage of Participants With Normal ALT at Week 96 by Central Laboratory and the AASLD Criteria

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.

Percentage of Participants With Normalized ALT at Week 48 by Central Laboratory and the AASLD Criteria

Percentage of Participants With Normalized ALT at Week 96 by Central Laboratory and the AASLD Criteria

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.

Change From Baseline in FibroTest® Score at Week 48

Change From Baseline in FibroTest® Score at 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.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT03180619

First Posted

June 6, 2017

Last Updated

August 30, 2021

Sponsor

Gilead Sciences

1. Study Identification

Unique Protocol Identification Number

NCT03180619

Brief Title

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)

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2021

Overall Recruitment Status

Completed

Study Start Date

June 29, 2017 (Actual)

Primary Completion Date

March 27, 2019 (Actual)

Study Completion Date

September 4, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Gilead Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Hepatitis B

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

124 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part A (Renal Impairment): Moderate or Severe Renal Impairment

Arm Type

Experimental

Arm Description

Arm Title

Part A (Renal Impairment): End Stage Renal Disease

Arm Type

Experimental

Arm Description

Arm Title

Part B: Hepatic Impairment

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

TAF

Other Intervention Name(s)

Vemlidy®

Intervention Description

Tablet administered orally once daily

Primary Outcome Measure Information:

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

Title

Percentage of Participants Who Experienced Graded Treatment-Emergent Adverse Events (AEs) at Week 24

Description

Time Frame

Week 24

Title

Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 24

Description

Time Frame

Week 24

Secondary Outcome Measure Information:

Title

Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 48

Description

Time Frame

Week 48

Title

Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 96

Description

Time Frame

Week 96

Title

Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 48

Description

Time Frame

Week 48

Title

Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 96

Description

Time Frame

Week 96

Title

Description

Time Frame

Baseline, Week 24

Title

Change From Baseline in eGFRcg in Participants With Moderate or Severe Renal Impairment and Hepatically Impaired Participants at Week 48

Description

Time Frame

Baseline, Week 48

Title

Change From Baseline in eGFRcg in Participants With Moderate or Severe Renal Impairment and Hepatically Impaired Participants at Week 96

Description

Time Frame

Baseline, Week 96

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Time Frame

Week 24

Title

Percentage of Participants With Normal ALT at Week 48 by Central Laboratory and the AASLD Criteria

Description

Time Frame

Week 48

Title

Percentage of Participants With Normal ALT at Week 96 by Central Laboratory and the AASLD Criteria

Description

Time Frame

Week 96

Title

Percentage of Participants With Normalized ALT at Week 24 by Central Laboratory and the AASLD Criteria

Description

Time Frame

Week 24

Title

Percentage of Participants With Normalized ALT at Week 48 by Central Laboratory and the AASLD Criteria

Description

Time Frame

Week 48

Title

Percentage of Participants With Normalized ALT at Week 96 by Central Laboratory and the AASLD Criteria

Description

Time Frame

Week 96

Title

Change From Baseline in FibroTest® Score at Week 24

Description

Time Frame

Baseline, Week 24

Title

Change From Baseline in FibroTest® Score at Week 48

Description

Time Frame

Baseline, Week 48

Title

Change From Baseline in FibroTest® Score at Week 96

Description

Time Frame

Week 96

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

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

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

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

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

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key Inclusion Criteria: All Participants (Parts A and B): Adult male or non-pregnant female individuals Documented evidence of chronic HBV infection Alanine aminotransferase (ALT) ≤ 10 × upper limit of normal (ULN) Part A Only (renal impairment): Maintained on TDF and/or other OAV treatment(s) for CHB for at least 48 weeks and with viral suppression (HBV deoxyribonucleic acid [DNA] < lower limit of quantitation [LLOQ]) for ≥ 6 months prior to screening All individuals must have HBV DNA < 20 International units per milliliter (IU/mL) at screening by central laboratory Both Hepatitis B e-Antigen (HBeAg) positive and negative individuals are eligible to participate Moderate renal impairment (30 milliliters per minute [mL/min] ≤ estimated glomerular filtration rate by the cockcroft-gault formula [eGFRcg] ≤ 59 mL/min), severe renal impairment (15 mL/min ≤ eGFRcg < 30 mL/min) or end stage renal disease (ESRD) (eGFR < 15 mL/min) maintained on hemodialysis (HD) Stable renal function (for participants with moderate or severe impairment): serum creatinine measured at least once within three months prior to screening. The measurement difference between the value measured within three months prior to screening versus the screening value must be ≤ 25% of the screening value Part B Only (hepatic impairment): Maintained on TDF and/or other OAV(s) for CHB for at least 48 weeks and with viral suppression (HBV DNA < LLOQ) for ≥ 6 months prior to screening All individuals must have HBV DNA < 20 IU/mL at screening by central laboratory Both HBeAg positive and negative individuals are eligible to participate Child-pugh-turcotte (CPT) score of 7-12 (inclusive) OR a past history of CPT score ≥ 7 and any CPT score ≤ 12 at screening eGFRCG ≥ 30 mL/min using the Cockcroft-Gault equation Key Exclusion Criteria: All Individuals (Parts A & B): Women who are breastfeeding or who believe they may wish to become pregnant during the course of the study Males and females of reproductive potential who are unwilling to use an "effective", protocol-specified method(s) of contraception during the study Co-infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or hepatitis D virus (HDV) Prior Interferon (IFN) use within 6 months of screening Evidence of hepatocellular carcinoma Received solid organ or bone marrow transplant Significant cardiovascular, pulmonary, or neurological disease Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc.). Individuals under evaluation for possible malignancy are not eligible Currently receiving therapy with immunomodulators (e.g. corticosteroids), nephrotoxic agents, or agents capable of modifying renal excretion Known hypersensitivity to study drugs, metabolites, or formulation excipients Current alcohol or substance abuse judged by the investigator to potentially interfere with individual's compliance Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the individual unsuitable for the study or unable to comply with dosing requirements. Part A Only (Renal Impairment): Current or historical evidence of clinical hepatic decompensation (e.g., ascites, encephalopathy or variceal hemorrhage) Abnormal hematological and biochemical parameters, including: Hemoglobin < 9 grams per deciliter (g/dL) Absolute neutrophil count < 750/cubic millimeter (mm^3) Platelets ≤ 50,000/mm^3 Aspartate aminotransferase (AST) > 10 × ULN Albumin < 3.0 g/dL Total bilirubin > 2.5 × ULN International normalized ratio of prothrombin time (INR) > 1.5 × ULN (unless stable on anticoagulant regimen) Individuals with ESRD (i.e. eGFRcg < 15 mL/min) not on HD, or those on other forms of renal replacement therapy (i.e. peritoneal dialysis) Part B Only (Hepatic Impairment): Active variceal bleeding within 6 months or prior placement of a portosystemic shunt (such as transjugular intrahepatic portosystemic shunt [TIPS]) History of hepatorenal syndrome, hepatopulmonary syndrome, Grade 3 or Grade 4 hepatic encephalopathy, or spontaneous bacterial peritonitis within 6 months of screening Grade 2 hepatic encephalopathy at screening Model for end-stage liver disease (MELD) score ≥ 30 Abnormal hematological and biochemical parameters, including Absolute neutrophil count < 750/mm^3 Platelets < 30,000/mm^3 Hemoglobin < 8.0 g/dL Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gilead Study Director

Organizational Affiliation

Gilead Sciences

Official's Role

Study Director

Facility Information:

Facility Name

Coalition of Inclusive Medicine

City

Los Angeles

State/Province

California

ZIP/Postal Code

90020

Country

United States

Facility Name

Silicon Valley Research Institute, Inc

City

San Jose

State/Province

California

ZIP/Postal Code

95128

Country

United States

Facility Name

Henry Ford Health System

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48202

Country

United States

Facility Name

Harborview Medical Center

City

Seattle

State/Province

Washington

ZIP/Postal Code

98104

Country

United States

Facility Name

University of Calgary Liver Unit

City

Calgary

ZIP/Postal Code

T2N4Z6

Country

Canada

Facility Name

Centre de Recherche du Centre Hospitalier de l'Universite de Montreal

City

Montreal

ZIP/Postal Code

H2X 0A9

Country

Canada

Facility Name

University Health Network,Toronto general Hospital,Toronto centre for liver disease

City

Toronto

ZIP/Postal Code

M5G 2C4

Country

Canada

Facility Name

Toronto Liver Centre

City

Toronto

ZIP/Postal Code

M6H 3M1

Country

Canada

Facility Name

(G.I.R.I.) GI Research Institute

City

Vancouver

ZIP/Postal Code

V6Z 2K5

Country

Canada

Facility Name

Prince of Wales Hospital

City

Shatin

State/Province

Country

Hong Kong

Facility Name

Princess Margaret Hospital

City

Kowloon

Country

Hong Kong

Facility Name

Alice Ho Miu Ling Nethersole Hospital

City

Tai Po

Country

Hong Kong

Facility Name

U.O. Medicina Generale Epatologia IRCCS Humanitas Centro di Ricerca Traslazionale in Epatologia

City

Rozzano

State/Province

Milan

ZIP/Postal Code

20089

Country

Italy

Facility Name

Dipartimento di Scienze Mediche e Chirurgiche (DIMEC) AOU Policlinico S.Orsola-Malpighi di Bologna

City

Bologna

ZIP/Postal Code

40138

Country

Italy

Facility Name

UOC Gastroenterol-Epatol.-Fondazione IRCCS Ca Granda

City

Milan

ZIP/Postal Code

20122

Country

Italy

Facility Name

Dong-A University Hospital

City

Busan

ZIP/Postal Code

49201

Country

Korea, Republic of

Facility Name

Pusan National University Hospital

City

Busan

ZIP/Postal Code

49241

Country

Korea, Republic of

Facility Name

Asan Medical Center

City

Seoul

ZIP/Postal Code

05505

Country

Korea, Republic of

Facility Name

Yonsei University Health System, Severance Hospital

City

Seoul

ZIP/Postal Code

120-752

Country

Korea, Republic of

Facility Name

Auckland Clinical Studies

City

Grafton

State/Province

Auckland

ZIP/Postal Code

1010

Country

New Zealand

Facility Name

Changhua Christian Hospital

City

Changhua

ZIP/Postal Code

500

Country

Taiwan

Facility Name

Ditmanson Medical Foundation Chia-Yi Christian Hospital

City

Chiayi City

ZIP/Postal Code

60002

Country

Taiwan

Facility Name

Kaohsiung Chang Gung Memorial Hospital

City

Kaohsiung City

ZIP/Postal Code

83301

Country

Taiwan

Facility Name

Kaohsiung Medical University Chung-Ho Memorial Hospital

City

Kaohsiung

ZIP/Postal Code

807

Country

Taiwan

Facility Name

Taichung Veterans Genl Hosp

City

Taichung

ZIP/Postal Code

40705

Country

Taiwan

Facility Name

National Taiwan University Hospital

City

Taipei

ZIP/Postal Code

10001

Country

Taiwan

Facility Name

Veterans General Hospital-Taipei

City

Taipei

ZIP/Postal Code

11217

Country

Taiwan

Facility Name

Chang Gung Medical Foundation, Linkou Chang Gung Memorial Hospital

City

Taoyuan City

ZIP/Postal Code

333

Country

Taiwan

Facility Name

Nottingham University Hospital

City

London

ZIP/Postal Code

NG7 2UH

Country

United Kingdom

Facility Name

King's College Hospital NHS Foundation Trust

City

London

ZIP/Postal Code

SE5 9RS

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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 URL

https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy

Citations:

Citation

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.

Results Reference

result

Citation

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.

Results Reference

result

Citation

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.

Results Reference

result

Citation

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.

Results Reference

result

Learn more about this trial

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)

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