Study to Compare Tenofovir Alafenamide (TAF) Versus Tenofovir Disoproxil Fumarate (TDF) in Participants With Chronic Hepatitis B Infection Who Are Negative for Hepatitis B e Antigen

NCT01940341 | Completed Phase 3 Results DMC

• 2 other identifiers: GS-US-320-01082013-000626-63
• Study Type: interventional
• Target: 426
• Locations: 17 countries
• Sites: 105

Brief Summary

The primary objective of this study is to compare the efficacy, safety, and tolerability of tenofovir alafenamide (TAF) versus tenofovir disoproxil fumarate (TDF) in treatment-naive and treatment-experienced adults with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV) infection.

Conditions

HBeAg-negative Chronic Hepatitis B

Keywords

Hepatitis; Tenofovir; Viread

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Hepatitis B Virus (HBV) DNA < 29 IU/mL

  The primary efficacy endpoint was determined by the achievement of HBV DNA \< 29 IU/mL at Week 48.

  Week 48

Secondary Outcomes (3)

• Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48

  Baseline, Week 48

• Percent Change From Baseline in Spine BMD at Week 48

  Baseline, Week 48

• Change From Baseline in Serum Creatinine at Week 48

  Baseline, Week 48

Other Outcomes (1)

• Percentage of Participants With Treatment-emergent Proteinuria by Urinalysis (Dipstick) Through Week 48

  Up to 48 weeks

Study Arms (3)

TAF 25 mg

EXPERIMENTAL

TAF + TDF placebo for 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3).

Drug: TAF; Drug: TDF Placebo

TDF 300 mg

ACTIVE COMPARATOR

TDF + TAF placebo for 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3).

Drug: TDF; Drug: TAF Placebo

Open-label TAF

EXPERIMENTAL

All participants who complete the double-blind period (96 weeks or 144 weeks) will be eligible to receive open-label TAF until Week 384 of the study. After the end of study treatment, participants can either switch to commercially available anti-HBV treatments in their country or will be followed every 4 weeks, for up to 24 weeks off treatment (treatment-free follow-up (TFFU)) for safety assessment.

Drug: TAF

Interventions

TAF DRUG

25 mg tablet administered orally once daily

Also known as: Vemlidy®, GS-7340

Open-label TAF; TAF 25 mg

TDF DRUG

300 mg tablet administered orally once daily

Also known as: Viread®

TDF 300 mg

TAF Placebo DRUG

Tablet administered orally once daily

TDF 300 mg

TDF Placebo DRUG

Tablet administered orally once daily

TAF 25 mg

Eligibility Criteria

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

You may qualify if:

• Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures.
• Adult males and non-pregnant, non-lactating females.
• Documented evidence of chronic HBV infection.
• Hepatitis e antigen (HBeAg)-negative, chronic hepatitis B with all of the following:
• HBeAg-negative and hepatitis B e antibody (HBeAb) positive at screening.
• Screening HBV DNA ≥ 2 x 10\^4 IU/mL.
• Screening serum alanine aminotransferase (ALT) level \> 60 U/L (males) or \> 38 U/L (females) and ≤ 10 x the upper limit of the normal range (ULN).
• Treatment-naive participants (defined as \< 12 weeks of oral antiviral treatment with any nucleoside or nucleotide analogue), OR treatment-experienced participants (defined as participants meeting all entry criteria \[including HBV DNA and serum ALT criteria\] and with ≥ 12 weeks of previous treatment with any nucleoside or nucleotide analogue).
• Previous treatment with interferon (pegylated or non pegylated) must have ended at least 6 months prior to Baseline.
• Adequate renal function.
• Normal electrocardiogram (ECG).

You may not qualify if:

• Females who are breastfeeding.
• 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, human immunodeficiency virus (HIV), or hepatitis D virus.
• Evidence of hepatocellular carcinoma.
• Any history of, or current evidence of, clinical hepatic decompensation.
• Abnormal hematological and biochemical parameters, including aspartate aminotransferase (AST) \> 10 x ULN
• Received solid organ or bone marrow transplant.
• History of malignancy within the past 5 years, with the exception of specific cancers that are cured by surgical resection; individuals under evaluation for possible malignancy are not eligible.
• Currently receiving therapy with immunomodulators (eg, corticosteroids), investigational agents, nephrotoxic agents, or agents capable of modifying renal excretion.
• Individuals receiving ongoing therapy with drugs not to be used with tenofovir alafenamide or tenofovir disoproxil fumarate or individuals with a known hypersensitivity to study drugs, metabolites, or formulation excipients.
• Current alcohol or substance abuse judged by the investigator to potentially interfere with participant compliance.
• Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the participant unsuitable for the study or unable to comply with dosing requirements.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (105)

Asian Pacific Liver Center

Los Angeles, California, 90020, United States

Location

Stanford University Medical Center

Palo Alto, California, 94304, United States

Location

Huntington Medical Research Institutes

Pasadena, California, 91105, United States

Location

Research and Education, Inc.

San Diego, California, 92105, United States

Location

University California San Francisco (UCSF)

San Francisco, California, 94110, United States

Location

Silicon Valley Research Institute

San Jose, California, 95128, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Digestive Disease Associates, PA

Catonsville, Maryland, 21228, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

ID Care

Hillsborough, New Jersey, 08844, United States

Location

Sing Chan Private Practice

Flushing, New York, 11354, United States

Location

New Discovery, LLC

Flushing, New York, 11355, United States

Location

Xiaoli Ma, PC

Philadelphia, Pennsylvania, 19107, United States

Location

Hunter Holmes McGuire VA DVMC

Richmond, Virginia, 23249, United States

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

St. Vincent's Hospital

Fitzroy, Victoria, 3065, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

Location

University of Calgary

Calgary, Alberta, T2N 4Z6, Canada

Location

Zeidler Ledcor Centre Division of Gastroenterology

Edmonton, Alberta, T6G 2X8, Canada

Location

Liver and Intestinal Research Centre

Vancouver, British Columbia, V5Z 1H3, Canada

Location

Gordon and Leslie Diamond Health Care Centre

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Dr. John Farley Inc.

Vancouver, British Columbia, V6A 4B6, Canada

Location

Vancouver Infectious Disease Research and Care Centre

Vancouver, British Columbia, V6Z 2C7, Canada

Location

Gastrointestinal Research Institute (GIRI)

Vancouver, British Columbia, V6Z 2K5, Canada

Location

University of Manitoba

Winnipeg, Manitoba, R3E 3P4, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Inspiration Research Limited

Toronto, Ontario, M5T 2S8, Canada

Location

Toronto Liver Centre

Toronto, Ontario, M6H 3M1, Canada

Location

Hôpital de la Croix Rousse

Lyon, 69317, France

Location

Hopital Civil de Strasbourg- CHU Service

Strasbourg, 67000, France

Location

Queen Mary Hospital

Hong Kong, Hong Kong SAR, Hong Kong

Location

Princess Margaret Hospital

Kwai Chung, Hong Kong

Location

Prince of Wales Hospital

Shatin, Hong Kong

Location

Alice Ho Miu Ling Nethersole Hospital

Tai Po, Hong Kong

Location

Global Hospitals

Hyderabad, Andhra Pradesh, 500004, India

Location

Centre for Liver Research & Diagnostic, Deccan College of Medical Sciences and Allied Hospitals

Hyderabad, Andhra Pradesh, 500058, India

Location

Nirmal Hospital

Surat, Gujarat, 395002, India

Location

Seth GS Medical College and KEM Hospital

Mumbai, Maharashtra, 400012, India

Location

Global Hospital Super Specialty & Transplant Centre

Pārel, Mumbai, 400 012, India

Location

All India Institute of Medical Sciences

New Delhi, National Capital Territory of Delhi, 110029, India

Location

S. R Kalla Memorial Gastro & General Hospital

Jaipur, Rajasthan, 302001, India

Location

Institute of Post Graduate Medical Education And Research

Kolkata, West Bengal, 700020, India

Location

Postgraduate Institute of Medical Education and Research

Chandigarh, 160012, India

Location

Institute of Liver and Biliary Sciences

New Delhi, 110070, India

Location

IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, Foggia, 71013, Italy

Location

Azienda Ospedaliera S. Orsola - Malpighi

Bologna, 40138, Italy

Location

Azienda Ospedaliero Universitaria Ospedali

Foggia, 71122, Italy

Location

Azienda Ospedaliero- Universitaria Pisana

Pisa, 56124, Italy

Location

Kurume University Hospital

Kurume-shi, Fukuoka, 830-0011, Japan

Location

Kyushu University Hospital Fukuoka

Fukuoka, Fukuoka-shi, 812-8582, Japan

Location

National Hospital Organization Nagasaki Medical Center

Omura-shi, Nagasaki, 856-8562, Japan

Location

Osaka University Hospital

Suita, Osaka, 565-0871, Japan

Location

Shin-Kokura Hospital

Kitakyushu, 803-8505, Japan

Location

Kobe City Medical Center General Hospital

Kobe, 650-0047, Japan

Location

Japan Red Cross Musashino Hospital

Musashino, 180-8610, Japan

Location

The Hospital of Hyogo College of Medicine

Nishinomiya, 663-8501, Japan

Location

Osaka Red Cross Hospital

Osaka, 543-8555, Japan

Location

Hokkaido University Hospital

Sapporo, 060-8648, Japan

Location

Medical Hospital of Tokyo Medical and Dental University

Tokyo, 113-8519, Japan

Location

Auckland Clinical Studies Limited

Auckland, 1010, New Zealand

Location

Uniwersytecki Szpital Kliniczny w Bialymstoku Klinika

Bialystok, 15-540, Poland

Location

Szpital Specjalistyczny w Chorzowie Oddział

Chorzów, 41-500, Poland

Location

SPZOZ, Wojewódzki Specjalistyczny Szpital

Lodz, 91-347, Poland

Location

Centrum Badan Klinicznych - Przychodnia Badan

Wroclaw, 50-349, Poland

Location

Institutul National de Boli Infectioase "Prof. Dr. Matei Bals"

Bucharest, București, 021105, Romania

Location

Centrul Medical de Diagnostic si Tratament "Dr. Victor Babes"

Bucharest, 030303, Romania

Location

Institutul National de Boli Infectioase Prof.Dr. Matei Bals

Bucharest, 21105, Romania

Location

Spitatul Clinic de Boli Infectioase Constanta

Constanța, 900708, Romania

Location

Gastromedica SRL

Iași, 700506, Romania

Location

Infection Center LLC Building 20, MSH #163 Territory Koltsovo

Kol'tsovo, Novosibirsk Oblast, 630559, Russia

Location

1st Moscow State Medical University University Clinical Hospital #3

Moscow, 119991, Russia

Location

Limited Liability Company "Modern Medicine Clinic"

Moscow, 121293, Russia

Location

Infectious Clinical Hospital #1 of Moscow Healthcare Department

Moscow, 125367, Russia

Location

Novosibirsk State Medical University

Novosibirsk, 630084, Russia

Location

State Novosibirsk Regional Clinical Hospital

Novosibirsk, 630087, Russia

Location

Scientific Research Institute of Clinical Immunology

Novosibirsk, 630091, Russia

Location

Clinical Infectious Hospital named after S.P.Botkin

Saint Petersburg, 191167, Russia

Location

Kirov Medical Military Academy

Saint Petersburg, 194044, Russia

Location

Research Institute of Influenza

Saint Petersburg, 197376, Russia

Location

Pusan National University Yangsan Hospital

Yangsan, Gyeongsangnam-do, 50612, South Korea

Location

Kyungpook National University Hospital

Daegu, 41944, South Korea

Location

Keimyung University Dongsan Medical Center

Daegu, 42601, South Korea

Location

Yonsei University, Severance Hospital

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Gangnam Severance Hospital

Seoul, 06273, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Seoul Saint Mary Hospital

Seoul, 06591, South Korea

Location

Chung-Ang University Hospital

Seoul, 06973, South Korea

Location

Korea University Guro Hospital

Seoul, 08308, South Korea

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hualien Tzu Chi Hospital

Hualien City, 970, Taiwan

Location

Kaohsiung Medical University Hospital

Kaohsiung City, 807, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Dicle University Medical Faculty Department of Infectious Diseases

Diyarbakır, Diyarbakri, 21280, Turkey (Türkiye)

Location

Ankara Üniversitesi Gastroenteroloji Bilim Dalı Cebeci

Ankara, 06590, Turkey (Türkiye)

Location

Uludag Üniversitesi Tıp Fakültesi Gastroenteroloji

Bursa, 16059, Turkey (Türkiye)

Location

Istanbul Universitesi Cerrahpassa Tip Fakultesi Hastanesi

Istanbul, 34098, Turkey (Türkiye)

Location

Ege Universitesi Tip Fakultesi Hastanesi

Izmir, 35040, Turkey (Türkiye)

Location

Nottingham University Hospitals NHS Trust

Nottingham, Nottinghamshire, NG7 2UH, United Kingdom

Location

Barts and The London NHS Trust Royal London Hospital

London, E1 1BB, United Kingdom

Location

King's College Hospital

London, SE5 9RS, United Kingdom

Location

Related Publications (7)

• Buti M, Lim YS, Chan HLY, Agarwal K, Marcellin P, Brunetto MR, Chuang WL, Janssen HLA, Fung SK, Izumi N, Jablkowski MS, Abdurakhmanov D, Abramov F, Wang H, Botros I, Yee LJ, Mateo R, Flaherty JF, Osinusi A, Pan CQ, Shalimar X, Seto WK, Gane EJ. Eight-year efficacy and safety of tenofovir alafenamide for treatment of chronic hepatitis B virus infection: Final results from two randomised phase 3 trials. Aliment Pharmacol Ther. 2024 Dec;60(11-12):1573-1586. doi: 10.1111/apt.18278. Epub 2024 Sep 27.

  PMID: 39327857 DERIVED

• Lim YS, Chan HLY, Ahn SH, Seto WK, Ning Q, Agarwal K, Janssen HLA, Pan CQ, Chuang WL, Izumi N, Fung S, Shalimar, Brunetto M, Hui AJ, Chang TT, Lim SG, Abramov F, Flaherty JF, Wang H, Yee LJ, Kao JH, Gane E, Hou J, Buti M. Tenofovir alafenamide and tenofovir disoproxil fumarate reduce incidence of hepatocellular carcinoma in patients with chronic hepatitis B. JHEP Rep. 2023 Jul 13;5(10):100847. doi: 10.1016/j.jhepr.2023.100847. eCollection 2023 Oct.

  PMID: 37771546 DERIVED

• Chan HLY, Buti M, Lim YS, Agarwal K, Marcellin P, Brunetto M, Chuang WL, Janssen HLA, Fung S, Izumi N, Abdurakhmanov D, Jablkowski M, Celen MK, Ma X, Caruntu F, Flaherty JF, Abramov F, Wang H, Camus G, Osinusi A, Pan CQ, Shalimar, Seto WK, Gane E; GS-US-320-0110 and GS-US-320-0108 investigators. Long-Term Treatment With Tenofovir Alafenamide for Chronic Hepatitis B Results in High Rates of Viral Suppression and Favorable Renal and Bone Safety. Am J Gastroenterol. 2024 Mar 1;119(3):486-496. doi: 10.14309/ajg.0000000000002468. Epub 2023 Aug 9.

  PMID: 37561058 DERIVED

• Cathcart AL, Chan HL, Bhardwaj N, Liu Y, Marcellin P, Pan CQ, Shalimar, Buti M, Cox S, Parhy B, Zhou E, Martin R, Chang S, Lin L, Flaherty JF, Kitrinos KM, Gaggar A, Izumi N, Lim YS. No Resistance to Tenofovir Alafenamide Detected through 96 Weeks of Treatment in Patients with Chronic Hepatitis B Infection. Antimicrob Agents Chemother. 2018 Sep 24;62(10):e01064-18. doi: 10.1128/AAC.01064-18. Print 2018 Oct.

  PMID: 30038044 DERIVED

• Seto WK, Asahina Y, Brown TT, Peng CY, Stanciu C, Abdurakhmanov D, Tabak F, Nguyen TT, Chuang WL, Inokuma T, Ikeda F, Santantonio TA, Habersetzer F, Ramji A, Lau AH, Suri V, Flaherty JF, Wang H, Gaggar A, Subramanian GM, Mukewar S, Brunetto MR, Fung S, Chan HL. Improved Bone Safety of Tenofovir Alafenamide Compared to Tenofovir Disoproxil Fumarate Over 2 Years in Patients With Chronic HBV Infection. Clin Gastroenterol Hepatol. 2018 Jun 20:S1542-3565(18)30633-5. doi: 10.1016/j.cgh.2018.06.023. Online ahead of print.

  PMID: 29933096 DERIVED

• Agarwal K, Brunetto M, Seto WK, Lim YS, Fung S, Marcellin P, Ahn SH, Izumi N, Chuang WL, Bae H, Sharma M, Janssen HLA, Pan CQ, Celen MK, Furusyo N, Shalimar D, Yoon KT, Trinh H, Flaherty JF, Gaggar A, Lau AH, Cathcart AL, Lin L, Bhardwaj N, Suri V, Mani Subramanian G, Gane EJ, Buti M, Chan HLY; GS-US-320-0110; GS-US-320-0108 Investigators. 96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection. J Hepatol. 2018 Apr;68(4):672-681. doi: 10.1016/j.jhep.2017.11.039. Epub 2018 Jan 17.

  PMID: 29756595 DERIVED

• Buti M, Gane E, Seto WK, Chan HL, Chuang WL, Stepanova T, Hui AJ, Lim YS, Mehta R, Janssen HL, Acharya SK, Flaherty JF, Massetto B, Cathcart AL, Kim K, Gaggar A, Subramanian GM, McHutchison JG, Pan CQ, Brunetto M, Izumi N, Marcellin P; GS-US-320-0108 Investigators. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of patients with HBeAg-negative chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol. 2016 Nov;1(3):196-206. doi: 10.1016/S2468-1253(16)30107-8. Epub 2016 Sep 22.

  PMID: 28404092 DERIVED

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Conditions

Hepatitis

Interventions

tenofovir alafenamide; Tenofovir

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

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 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2013
• First Posted: September 12, 2013
• Study Start: September 12, 2013
• Primary Completion: September 30, 2015
• Study Completion: August 31, 2022
• Last Updated: September 25, 2023
• Results First Posted: March 30, 2017

Record last verified: 2023-09

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

GB (3); PL (4); IN (10); JP (11); KR (10); RU (10); IT (4); ES (1); US (14); TU (5); RO (5); TW (5); AU (5); HK (4); FR (2); CA (11); NZ (1)