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)

NCT03180619 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: GS-US-320-40352016-004625-16
• Study Type: interventional
• Target: 124
• Locations: 8 countries
• Sites: 30

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

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (48)

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

  Week 48

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

  Week 96

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

  Week 48

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

  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

  Baseline, Week 24

Study Arms (3)

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

EXPERIMENTAL

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

Part A (Renal Impairment): End Stage Renal Disease

EXPERIMENTAL

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

Part B: Hepatic Impairment

EXPERIMENTAL

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

Interventions

TAF DRUG

Tablet administered orally once daily

Also known as: Vemlidy®

Part A (Renal Impairment): End Stage Renal Disease; Part A (Renal Impairment): Moderate or Severe Renal Impairment; Part B: Hepatic Impairment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (30)

Coalition of Inclusive Medicine

Los Angeles, California, 90020, United States

Location

Silicon Valley Research Institute, Inc

San Jose, California, 95128, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

University of Calgary Liver Unit

Calgary, T2N4Z6, Canada

Location

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

Montreal, H2X 0A9, Canada

Location

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

Toronto, M5G 2C4, Canada

Location

Toronto Liver Centre

Toronto, M6H 3M1, Canada

Location

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

Vancouver, V6Z 2K5, Canada

Location

Prince of Wales Hospital

Shatin, NT, Hong Kong

Location

Princess Margaret Hospital

Kowloon, Hong Kong

Location

Alice Ho Miu Ling Nethersole Hospital

Tai Po, Hong Kong

Location

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

Rozzano, Milan, 20089, Italy

Location

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

Bologna, 40138, Italy

Location

UOC Gastroenterol-Epatol.-Fondazione IRCCS Ca Granda

Milan, 20122, Italy

Location

Auckland Clinical Studies

Grafton, Auckland, 1010, New Zealand

Location

Dong-A University Hospital

Busan, 49201, South Korea

Location

Pusan National University Hospital

Busan, 49241, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Yonsei University Health System, Severance Hospital

Seoul, 120-752, South Korea

Location

Changhua Christian Hospital

Changhua, 500, Taiwan

Location

Ditmanson Medical Foundation Chia-Yi Christian Hospital

Chiayi City, 60002, Taiwan

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807, Taiwan

Location

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 83301, Taiwan

Location

Taichung Veterans Genl Hosp

Taichung, 40705, Taiwan

Location

National Taiwan University Hospital

Taipei, 10001, Taiwan

Location

Veterans General Hospital-Taipei

Taipei, 11217, Taiwan

Location

Chang Gung Medical Foundation, Linkou Chang Gung Memorial Hospital

Taoyuan, 333, Taiwan

Location

Nottingham University Hospital

London, NG7 2UH, United Kingdom

Location

King's College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

Related Publications (6)

• 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.

  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.

  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.

  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.

  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.

  PMID: 40744841 DERIVED

• 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.

  PMID: 38901444 DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

tenofovir alafenamide

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2017
• First Posted: June 8, 2017
• Study Start: June 29, 2017
• Primary Completion: March 27, 2019
• Study Completion: September 4, 2020
• Last Updated: September 27, 2021
• Results First Posted: April 9, 2020

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.

Locations

CA (5); NZ (1); TW (8); US (4); GB (2); HK (3); IT (3); KR (4)