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

Phase 3

Completed

• Conditions: HBeAg-negative Chronic Hepatitis B
• Interventions: Drug: TAF; Drug: TDF; Drug: TDF Placebo; Drug: TAF Placebo

• Registration Number: NCT01940341
• Lead Sponsor: Gilead Sciences

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.

Detailed Description

Study GS-US-320-0108 is a multi-center clinical trial, planned to enroll participants in multiple countries, including China. However, due to the review timeline difference in China, full enrollment was reached in the main study before China was able to participate. Therefore, details for the China cohort was registered separately (NCT02836236) on ClinicalTrials.gov as the China cohort will not be part of the main study analysis.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2013-08-20
• Study First Submitted QC: 2013-09-09
• Study Start: 2013-09-12
• Study First Posted: 2013-09-12
• Primary Completion: 2015-09-30
• Disposition First Submitted: 2016-08-23
• Disposition First Submitted QC: 2016-08-23
• Disposition First Posted: 2016-08-25
• Results First Submitted: 2016-12-09
• Results First Submitted QC: 2017-02-10
• Results First Posted: 2017-03-30
• Study Completion: 2022-08-31
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-22
• Last Update Posted: 2023-09-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 426

Inclusion Criteria

• 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).

Key

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Exclusion Criteria

• 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.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TAF 25 mg	TAF	TAF + TDF placebo for 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3).
TAF 25 mg	TDF Placebo	TAF + TDF placebo for 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3).
TDF 300 mg	TAF Placebo	TDF + TAF placebo for 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3).
Open-label TAF	TAF	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.
TDF 300 mg	TDF	TDF + TAF placebo for 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3).

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Hepatitis B Virus (HBV) DNA < 29 IU/mL	Week 48	The primary efficacy endpoint was determined by the achievement of HBV DNA \< 29 IU/mL at Week 48.

Secondary Outcome Measures

Name	Time	Method
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48	Baseline, Week 48
Change From Baseline in Serum Creatinine at Week 48	Baseline, Week 48
Percent Change From Baseline in Spine BMD at Week 48	Baseline, Week 48

Trial Locations

Locations (105)

University of Miami; 🇺🇸 Miami, Florida, United States

Spitatul Clinic de Boli Infectioase Constanta; 🇷🇴 Constanta, Romania

Barts and The London NHS Trust Royal London Hospital; 🇬🇧 London, United Kingdom

All India Institute of Medical Sciences; 🇮🇳 New Delhi, Delhi, India

Postgraduate Institute of Medical Education and Research; 🇮🇳 Chandigarh, India

Institutul National de Boli Infectioase "Prof. Dr. Matei Bals"; 🇷🇴 Bucharest, Bucuresti, Romania

Royal Melbourne Hospital; 🇦🇺 Parkville, Victoria, Australia

Global Hospitals; 🇮🇳 Hyderabad, Andhra Pradesh, India

Centre for Liver Research & Diagnostic, Deccan College of Medical Sciences and Allied Hospitals; 🇮🇳 Hyderabad, Andhra Pradesh, India

SPZOZ, Wojewódzki Specjalistyczny Szpital; 🇵🇱 Lodz, Poland

IRCCS Ospedale Casa Sollievo della Sofferenza; 🇮🇹 San Giovanni Rotondo, Foggia, Italy

Clinical Infectious Hospital named after S.P.Botkin; 🇷🇺 Saint-Petersburg, Russian Federation

Kaohsiung Medical University Hospital; 🇨🇳 Kaohsiung, Taiwan

Osaka University Hospital; 🇯🇵 Suita, Osaka, Japan

Japan Red Cross Musashino Hospital; 🇯🇵 Musashino, Japan

Osaka Red Cross Hospital; 🇯🇵 Osaka, Japan

Hokkaido University Hospital; 🇯🇵 Sapporo, Japan

Medical Hospital of Tokyo Medical and Dental University; 🇯🇵 Tokyo, Japan

Uniwersytecki Szpital Kliniczny w Bialymstoku Klinika; 🇵🇱 Bialystok, Poland

Infectious Clinical Hospital #1 of Moscow Healthcare Department; 🇷🇺 Moscow, Russian Federation

Research Institute of Influenza; 🇷🇺 Saint-Petersburg, Russian Federation

Research and Education, Inc.; 🇺🇸 San Diego, California, United States

Azienda Ospedaliero Universitaria Ospedali; 🇮🇹 Foggia, Italy

New Discovery, LLC; 🇺🇸 Flushing, New York, United States

University of Calgary; 🇨🇦 Calgary, Alberta, Canada

Monash Medical Centre; 🇦🇺 Clayton, Victoria, Australia

St. Vincent's Hospital; 🇦🇺 Fitzroy, Victoria, Australia

Henry Ford Health System; 🇺🇸 Detroit, Michigan, United States

Sing Chan Private Practice; 🇺🇸 Flushing, New York, United States

Zeidler Ledcor Centre Division of Gastroenterology; 🇨🇦 Edmonton, Alberta, Canada

Sir Charles Gairdner Hospital; 🇦🇺 Nedlands, Western Australia, Australia

Xiaoli Ma, PC; 🇺🇸 Philadelphia, Pennsylvania, United States

Toronto General Hospital; 🇨🇦 Toronto, Ontario, Canada

Gordon and Leslie Diamond Health Care Centre; 🇨🇦 Vancouver, British Columbia, Canada

Hôpital de la Croix Rousse; 🇫🇷 Lyon cedex 04, France

Royal Perth Hospital; 🇦🇺 Perth, Western Australia, Australia

Hunter Holmes McGuire VA DVMC; 🇺🇸 Richmond, Virginia, United States

University of Manitoba; 🇨🇦 Winnipeg, Manitoba, Canada

Seth GS Medical College and KEM Hospital; 🇮🇳 Mumbai, Maharastra, India

Global Hospital Super Specialty & Transplant Centre; 🇮🇳 Parel, Mumbai, India

Hopital Civil de Strasbourg- CHU Service; 🇫🇷 Strasbourg, France

S. R Kalla Memorial Gastro & General Hospital; 🇮🇳 Jaipur, Rajasthan, India

Liver and Intestinal Research Centre; 🇨🇦 Vancouver, British Columbia, Canada

Gastrointestinal Research Institute (GIRI); 🇨🇦 Vancouver, British Columbia, Canada

Nirmal Hospital; 🇮🇳 Surat, Gujarat, India

Dr. John Farley Inc.; 🇨🇦 Vancouver, British Columbia, Canada

Vancouver Infectious Disease Research and Care Centre; 🇨🇦 Vancouver, British Columbia, Canada

ID Care; 🇺🇸 Hillsborough, New Jersey, United States

Inspiration Research Limited; 🇨🇦 Toronto, Ontario, Canada

Kurume University Hospital; 🇯🇵 Kurume-shi, Fukuoka-ken, Japan

Kobe City Medical Center General Hospital; 🇯🇵 Kobe, Japan

Azienda Ospedaliera S. Orsola - Malpighi; 🇮🇹 Bologna, Italy

Kyushu University Hospital Fukuoka; 🇯🇵 Fukuoka, Fukuoka-shi, Japan

National Hospital Organization Nagasaki Medical Center; 🇯🇵 Omura-shi, Nagasaki, Japan

Novosibirsk State Medical University; 🇷🇺 Novosibirsk, Russian Federation

State Novosibirsk Regional Clinical Hospital; 🇷🇺 Novosibirsk, Russian Federation

Scientific Research Institute of Clinical Immunology; 🇷🇺 Novosibirsk, Russian Federation

1st Moscow State Medical University University Clinical Hospital #3; 🇷🇺 Moscow, Russian Federation

Hospital Universitari Vall d'Hebron; 🇪🇸 Barcelona, Spain

Ankara Üniversitesi Gastroenteroloji Bilim Dalı Cebeci; 🇹🇷 Ankara, Turkey

Toronto Liver Centre; 🇨🇦 Toronto, Ontario, Canada

Asian Pacific Liver Center; 🇺🇸 Los Angeles, California, United States

Stanford University Medical Center; 🇺🇸 Palo Alto, California, United States

University California San Francisco (UCSF); 🇺🇸 San Francisco, California, United States

Silicon Valley Research Institute; 🇺🇸 San Jose, California, United States

Huntington Medical Research Institutes; 🇺🇸 Pasadena, California, United States

Digestive Disease Associates, PA; 🇺🇸 Catonsville, Maryland, United States

Institute of Post Graduate Medical Education And Research; 🇮🇳 Kolkata, West Bengal, India

Azienda Ospedaliero- Universitaria Pisana; 🇮🇹 Pisa, Italy

Shin-Kokura Hospital; 🇯🇵 Kitakyushu, Japan

The Hospital of Hyogo College of Medicine; 🇯🇵 Nishinomiya, Japan

Pusan National University Yangsan Hospital; 🇰🇷 Yangsan, Gyeongsangnam-do, Korea, Republic of

Keimyung University Dongsan Medical Center; 🇰🇷 Daegu, Korea, Republic of

Yonsei University, Severance Hospital; 🇰🇷 Seoul, Korea, Republic of

Kyungpook National University Hospital; 🇰🇷 Daegu, Korea, Republic of

Auckland Clinical Studies Limited; 🇳🇿 Auckland, New Zealand

Szpital Specjalistyczny w Chorzowie Oddział; 🇵🇱 Chorzow, Poland

Centrum Badan Klinicznych - Przychodnia Badan; 🇵🇱 Wroclaw, Poland

Institutul National de Boli Infectioase Prof.Dr. Matei Bals; 🇷🇴 Bucuresti, Romania

Centrul Medical de Diagnostic si Tratament "Dr. Victor Babes"; 🇷🇴 Bucuresti, Romania

Gastromedica SRL; 🇷🇴 Iasi, Romania

Infection Center LLC Building 20, MSH #163 Territory Koltsovo; 🇷🇺 Koltsovo, Novosibirsk, Russian Federation

Limited Liability Company "Modern Medicine Clinic"; 🇷🇺 Moscow, Russian Federation

Kirov Medical Military Academy; 🇷🇺 Saint-Petersburg, Russian Federation

Hualien Tzu Chi Hospital; 🇨🇳 Hualien City, Taiwan

Taichung Veterans General Hospital; 🇨🇳 Taichung, Taiwan

National Cheng Kung University Hospital; 🇨🇳 Tainan, Taiwan

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

Dicle University Medical Faculty Department of Infectious Diseases; 🇹🇷 Diyarbakir, Diyarbakri, Turkey

Ege Universitesi Tip Fakultesi Hastanesi; 🇹🇷 Izmir, Turkey

Istanbul Universitesi Cerrahpassa Tip Fakultesi Hastanesi; 🇹🇷 Istanbul, Turkey

Uludag Üniversitesi Tıp Fakültesi Gastroenteroloji; 🇹🇷 Bursa, Turkey

Nottingham University Hospitals NHS Trust; 🇬🇧 Nottingham, Nottinghamshire, United Kingdom

King's College Hospital; 🇬🇧 London, United Kingdom

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Gangnam Severance Hospital; 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Seoul Saint Mary Hospital; 🇰🇷 Seoul, Korea, Republic of

Chung-Ang University Hospital; 🇰🇷 Seoul, Korea, Republic of

Korea University Guro Hospital; 🇰🇷 Seoul, Korea, Republic of

Institute of Liver and Biliary Sciences; 🇮🇳 New Delhi, India

Princess Margaret Hospital; 🇭🇰 Kwai Chung, Hong Kong

Queen Mary Hospital; 🇭🇰 Hong Kong, Hong Kong SAR, Hong Kong

Alice Ho Miu Ling Nethersole Hospital; 🇭🇰 Tai Po, Hong Kong

Prince of Wales Hospital; 🇭🇰 Shatin, Hong Kong