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)

NCT ID: NCT03180619

Last Updated: 2021-09-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 124 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-29
• Study Completion Date: 2020-09-04

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.

Conditions

Chronic Hepatitis B

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

TAF

Intervention Type: DRUG

Tablet administered orally once daily

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.

Group Type: EXPERIMENTAL

TAF

Intervention Type: DRUG

Tablet administered orally once daily

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.

Group Type: EXPERIMENTAL

TAF

Intervention Type: DRUG

Tablet administered orally once daily

Interventions

TAF

Tablet administered orally once daily

Intervention Type: DRUG

Other Intervention Names

Vemlidy®

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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

Princess Margaret Hospital

Kowloon, , Hong Kong

Alice Ho Miu Ling Nethersole Hospital

Tai Po, , Hong Kong

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

Rozzano, Milan, Italy

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

Bologna, , Italy

UOC Gastroenterol-Epatol.-Fondazione IRCCS Ca Granda

Milan, , Italy

Auckland Clinical Studies

Grafton, Auckland, New Zealand

Dong-A University Hospital

Busan, , South Korea

Pusan National University Hospital

Busan, , South Korea

Asan Medical Center

Seoul, , South Korea

Yonsei University Health System, Severance Hospital

Seoul, , South Korea

Changhua Christian Hospital

Changhua, , Taiwan

Ditmanson Medical Foundation Chia-Yi Christian Hospital

Chiayi City, , Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, , Taiwan

Taichung Veterans Genl Hosp

Taichung, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Veterans General Hospital-Taipei

Taipei, , Taiwan

Chang Gung Medical Foundation, Linkou Chang Gung Memorial Hospital

Taoyuan, , Taiwan

Nottingham University Hospital

London, , United Kingdom

King's College Hospital NHS Foundation Trust

London, , United Kingdom

Countries

United States; Canada; Hong Kong; Italy; New Zealand; South Korea; Taiwan; United Kingdom

References

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.

Reference Type: RESULT

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.

Reference Type: RESULT

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.

Reference Type: RESULT

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.

Reference Type: RESULT

Liu CJ, Lim YS, Chen CY, Chen CH, Huang YH, Lin CY, Lin CC, Yu ML, Abramov F, Yee LJ, Duan R, Flaherty JF, Su WW, Yang SS, Janssen HLA, Chuang WL. Switching to tenofovir alafenamide in virally-suppressed chronic hepatitis B patients with renal/hepatic impairment: Phase 2 study sub-analysis from Taiwan. J Formos Med Assoc. 2025 Jul 30:S0929-6646(25)00390-0. doi: 10.1016/j.jfma.2025.07.023. Online ahead of print.

Reference Type: DERIVED

PMID: 40744841 (View on PubMed)

Janssen HLA, Lim YS, Lampertico P, Heo J, Chen CY, Fournier C, Tsang TYO, Bae H, Chen CH, Coffin CS, Ahn SH, Trinh H, Flaherty JF, Abramov F, Zhao Y, Liu Y, Lau A, German P, Chuang WL, Agarwal K, Gane E. Switching to tenofovir alafenamide in patients with virologically suppressed chronic hepatitis B and renal or hepatic impairment: final week 96 results from an open-label, multicentre, phase 2 study. Lancet Gastroenterol Hepatol. 2024 Aug;9(8):718-733. doi: 10.1016/S2468-1253(24)00096-7. Epub 2024 Jun 17.

Reference Type: DERIVED

PMID: 38901444 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-004625-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-320-4035

Identifier Type: -

Identifier Source: org_study_id