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)

Gilead Sciences124 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

124

Conditions

Chronic Hepatitis B

Interventions

TAFDRUG

Tablet administered orally once daily

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (30)

Outcomes

Primary Outcomes

Percentage of Participants Achieving Virologic Response (Plasma Hepatitis B Virus [HBV] Deoxyribonucleic Acid [DNA] < 20 IU/mL) at Week 24

The percentage of participants with HBV DNA \< 20 IU/mL at Week 24 was determined by the Missing = Failure (M = F) approach.

Time frame: Week 24

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

Treatment-emergent AEs were defined as: * Any AEs with an onset date on or after the study drug start date and no later than the study drug stop date + 3 days after permanent discontinuation of study drug; * Any AEs with onset date on or after the study drug start date for those who have not permanently discontinued study drug; * Any AEs leading to premature discontinuation of study drug. The most severe graded AE from all tests was counted for each participant.

Time frame: Week 24

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

Graded treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any postbaseline visit, up to and including the date of last dose of study drug + 3 days for participants who permanently discontinued study drug or the last available date in the database snapshot for participants who were on treatment at the time of the analysis. The most severe graded abnormality from all tests was counted for each participant.

Time frame: Week 24

Secondary Outcomes

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.

Data from ClinicalTrials.gov

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Coalition of Inclusive Medicine

Los Angeles, California, United States

Silicon Valley Research Institute, Inc

San Jose, California, United States

Henry Ford Health System

Detroit, Michigan, United States

Harborview Medical Center

Seattle, Washington, United States

University of Calgary Liver Unit

Calgary, Canada

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

Montreal, Canada

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

Toronto, Canada

Toronto Liver Centre

Toronto, Canada

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

Vancouver, Canada

Prince of Wales Hospital

Shatin, NT, Hong Kong

...and 20 more locations

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

Time frame: Week 96

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

Time frame: 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.

Time frame: 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.

Time frame: Baseline, Week 24

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

Time frame: Baseline, Week 48

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

Time frame: Baseline, Week 96

Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 24