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

HBeAg-positive Chronic Hepatitis B Clinical Trial

Official title:

A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Tenofovir Alafenamide (TAF) 25 mg QD Versus Tenofovir Disoproxil Fumarate (TDF) 300 mg QD for the Treatment of HBeAg-Positive, Chronic Hepatitis B

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01940471
• Other study ID #: GS-US-320-0110
• Secondary ID: 2013-000636-10
• Status: Completed
• Phase: Phase 3
• Start date: September 11, 2013
• Est. completion date: October 13, 2022

Study information

• Verified date: September 2023
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)-positive chronic hepatitis B virus (HBV) infection.

Description:

This study GS-US-320-0110 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 are registered separately (NCT02836249) on ClinicalTrials.gov as this cohort will not be part of the main study analysis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 875
• Est. completion date: October 13, 2022
• Est. primary completion date: November 16, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key 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.

• HBeAg-positive, chronic hepatitis B with all of the following:

• HBeAg-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 the baseline visit.

• Adequate renal function.

• Normal electrocardiogram (ECG).

Key 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.

Related Conditions & MeSH terms

• HBeAg-positive Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• TAF
25 mg tablet administered orally once daily
• TDF
300 mg tablet administered orally once daily
• TAF Placebo
Tablet administered orally once daily
• TDF Placebo
Tablet administered orally once daily

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	St. Vincent's Hospital	Fitzroy	Victoria
Australia	Footscray Hospital	Footscray	Victoria
Australia	Austin Health	Heidelberg	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	The Royal Melbourne Hospital	Parkville	Victoria
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Westmead Hospital Westmead	Westmead	New South Wales
Bulgaria	MHAT Alexandrovska Medical University, Sofia	Sofia
Bulgaria	MHAT Sofia Med	Sofia
Bulgaria	MMA Hospital of Active Treatment	Sofia
Bulgaria	Tokuda Hospital - Sofia	Sofia
Canada	University of Calgary	Calgary	Alberta
Canada	Zeidler Ledcor Centre Division of Gastroenterology / Department of Medicine	Edmonton	Alberta
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	Inspiration Research Limited	Toronto	Ontario
Canada	Toronto Liver Centre	Toronto	Ontario
Canada	University Health Network / Toronto General Hospital	Toronto	Ontario
Canada	Dr. John Farley, Inc.	Vancouver	British Columbia
Canada	Gastrointestinal Research Institute (GIRI)	Vancouver	British Columbia
Canada	Gordon and Leslie Diamond Health Care Centre	Vancouver	British Columbia
Canada	Liver and Intestinal Research Centre	Vancouver	British Columbia
Canada	Vancouver Infectious Disease Research and Care Centre	Vancouver	British Columbia
Canada	University of Manitoba, Health Sciences Center	Winnipeg	Manitoba
France	Hopital Beaujon	Clichy
France	Hopital Pitie Salpetriere	Paris
France	Hopital Civil de Strasbourg	Strasbourg
France	Hopital Paul Brousse	Villejuif
Hong Kong	Queen Mary Hospital	Hong Kong
Hong Kong	Princess Margaret Hospital	Lai Chi Kok
Hong Kong	Prince of Wales Hospital	Sha Tin
Hong Kong	Alice Ho Miu Ling Nethersole Hospital	Tai Po
Hong Kong	Tuen Mun Hospital	Tuen Mun
India	Postgraduate Institute of Medical Education & Research	Chandigarh
India	YR Gaitonde Centre for AIDS Research and Education	Chennai
India	VGM Hospital	Coimbatore
India	Centre for Liver Research & Diagnostic, Deccan College of Medical Sciences and Allied Hospitals	Hyderabad
India	Gleneagles Global Hospital	Hyderabad
India	S. R Kalla Memorial Gastro & General Hospital	Jaipur
India	SMS Medical College & Hospital	Jaipur	Rajasthan
India	Peerless Hospital & B.K.Roy Research Center	Kolkata
India	Postgraduate Institute of Medical Education & Research	Kolkata
India	BYL Nair Hospital & T N Medical College	Mumbai	Maharashtra
India	Seth GS Medical College and KEM Hospital	Mumbai
India	Government Medical College and Superspecialty Hospital	Nagpur	Maharashtra
India	Midas Multispecialty Hospital	Nagpur	Maharashtra
India	All India Institute of Medical Sciences	New Delhi
India	Institute of Liver and Biliary Sciences	New Delhi
India	Sir Ganga Ram Hospital	New Delhi
India	Global Hospital Super Specialty & Transplant Centre	Parel
India	Nirmal Hospital	Surat
Italy	Azienda Ospedaliera di Bologna - Policlinico S. Orsola Malpighi	Bologna
Italy	Istituto Europeo di Oncologia	Bologna
Italy	Azienda Ospedaliero Universitaria Ospedali Riuniti di	Foggia
Italy	Policlinico Universitario G. Martino via Consolare	Messina
Italy	Azienda Ospedale San Paolo	Milano
Italy	Azienda Ospedaliera di Padova	Padova
Italy	Azienda Ospedaliera di Padova	Padova
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Japan	Kyushu University Hospital	Fukuoka	Fukuoka-shi
Japan	National Hospital Organization Kyushu Medical Center	Fukuoka
Japan	Shin-Kokura Hospital	Fukuoka
Japan	Kagawa Prefectural Central Hospital	Kagawa
Japan	Kobe City Medical Center General Hospital	Kobe
Japan	Yamanashi Prefectural Central Hospital	Kofu
Japan	Kurume University Hospital	Kurume
Japan	Kyoto Prefectural University of Medicine	Kyoto
Japan	Japan Red Cross Musashino Hospital	Musashino
Japan	Hyogo College of Medicine	Nishinomiya
Japan	Okayama University Hospital	Okayama
Japan	National Hospital Organization Nagasaki Medical Center	Omura
Japan	Osaka Red Cross Hospital	Osaka
Japan	Osaka University Hospital	Osaka
Japan	Hokkaido University Hospital	Sapporo
Japan	Medical Hospital of Tokyo Medical and Dental University	Tokyo
Korea, Republic of	Kosin University College of Medicine	Busan	Seo-gu
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	SoonChunHyang University Hospital Cheonan	Cheonan
Korea, Republic of	Keimyung University Dongsan Medical Center	Daegu
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Konyang University Hospital	Daejeon
Korea, Republic of	Ajou University Hospital	Gyeonggi-do
Korea, Republic of	Inje University Ilsan Paik Hospital	Gyeonggi-do
Korea, Republic of	Seoul National University Bundang Hospital	Gyeonggi-Do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Chung-Ang University Hospital	Seoul
Korea, Republic of	Gangnam Severance Hospital	Seoul
Korea, Republic of	Konkuk University Medical Center	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Seoul Saint Mary Hospital	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
Korea, Republic of	SMG-SNU Boramae Medical Center	Seoul
Korea, Republic of	Ulsan University Hospital	Ulsan
Korea, Republic of	Yonsei Unversity Wonju	Wonju
Korea, Republic of	Pusan National University Yangsan Hospital	Yangsan
New Zealand	Auckland Clinical Studies Limited	Auckland
New Zealand	Waikato Hospital (District Health Board)	Hamilton
Poland	Uniwersytecki Szpital Kliniczny w Bialymstoku Klinika	Bialystok
Poland	Szpital Specjalistyczny	Chorzow
Poland	SPZOZ, Wojewódzki Specjalistyczny Szpital	Lodz
Poland	SP ZOZ Wojewódzki Szpital Zakazny	Warszawa
Poland	Centrum Badan Klinicznych	Wroclaw
Romania	Centrul Medical de Diagnostic si Tratament "Dr. Victor Babes"	Bucharest
Romania	Institutul National de Boli Infectioase "Prof. Dr. Matei Bals"	Bucuresti
Romania	Spitatul Clinic de Boli Infectioase Constanta	Constanta
Romania	Gastromedica SRL	Iasi
Romania	Spitalul Clinic Judetean de Urgenta Timisoara	Timisoara
Russian Federation	Lipetsk Regional Center for Prevention and Control of AIDS and Infectious Diseases	Lipetsk
Russian Federation	1st Moscow State Medical University University Clinical Hospital #3	Moscow
Russian Federation	Limited Liability Company "Modern Medicine Clinic"	Moscow
Russian Federation	People's Friendship University of Russia	Moscow
Russian Federation	Scientific Research Institute of Nutrition	Moscow
Russian Federation	Institute of Clinical Immunology RAMS, Clinic of Immunopathology	Novosibirsk
Russian Federation	Scientific Research Institute of Clinical Immunology	Novosibirsk
Russian Federation	Municipal Clinical Hospital n.a. S.P. Botkin	Saint-Petersburg
Russian Federation	Research Institute of Influenza	Saint-Petersburg
Russian Federation	Medical Company Hepatology	Samara
Russian Federation	Sverdlovsk Regional Clinical Hospital #1	Yekaterinburg
Singapore	Changi General Hospital Pte Ltd.	Singapore
Singapore	National University Hospital Singapore	Singapore
Singapore	Singapore General Hospital	Singapore
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Taiwan	Chiayi Christian Hospital	Chiayi
Taiwan	Hualien Tzu Chi Medical Center	Hualien
Taiwan	Kaohsiung Med. College Hosp. Dept. of Internal Medicine	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	Cathay General Hospital	Taipei
Taiwan	Far-Eastern Memorial Hospital	Taipei
Taiwan	National Taiwan University Hospital	Taipei
Turkey	Ankara Üniversitesi Gastroenteroloji Bilim Dali Cebeci	Ankara
Turkey	University of Uludag	Bursa
Turkey	Dicle University Medical Faculty Department of Infectious Diseases	Diyarbakir
Turkey	Istanbul Universitesi Cerrahpassa Tip Fakultesi Enfeksiyon	Istanbul
Turkey	Ege Universitesi Tip Fakultesi Hastanesi	Izmir
United Kingdom	Barts & The London NHS Trust	London
United Kingdom	King's College Hospital	London
United Kingdom	Royal Free Hospital	London
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham
United States	Texas Clinical Research Institute, LLC	Arlington	Texas
United States	Tufts Medical Center, Inc	Boston	Massachusetts
United States	Digestive Disease Associates, PA	Catonsville	Maryland
United States	Henry Ford Health System	Detroit	Michigan
United States	New Discovery, LLC	Flushing	New York
United States	Sing Chan Private Practice	Flushing	New York
United States	Kelsey Research Foundation	Houston	Texas
United States	Coalition of Inclusive Medicine	Los Angeles	California
United States	University of Miami	Miami	Florida
United States	Stanford University Medical Center	Palo Alto	California
United States	Huntington Medical Research Institutes	Pasadena	California
United States	Jefferson Medical College	Philadelphia	Pennsylvania
United States	Xiaoli Ma, PC	Philadelphia	Pennsylvania
United States	Research and Education, Inc.	San Diego	California
United States	Silicon Valley Research Institute	San Jose	California

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Canada,  France,  Hong Kong,  India,  Italy,  Japan,  Korea, Republic of,  New Zealand,  Poland,  Romania,  Russian Federation,  Singapore,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of Participants With Treatment-emergent Proteinuria by Urinalysis (Dipstick) Through Week 48	Grades 1 (mild), 2 (moderate), and 3 (severe) were the highest treatment-emergent postbaseline grades for urine protein using the dipstick method.	Up to 48 weeks
Primary	Percentage of Participants With Hepatitis B Virus (HBV) DNA < 29 IU/mL at Week 48		Week 48
Secondary	Percentage of Participants With Hepatitis B e Antigen (HBeAg) Seroconversion to Antibody Against Hepatitis B e Antigen (Anti-HBe) at Week 48		Week 48
Secondary	Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48		Baseline, Week 48
Secondary	Percent Change From Baseline in Spine BMD at Week 48		Baseline, Week 48
Secondary	Change From Baseline at Week 48 in Serum Creatinine		Baseline, Week 48

External Links

•   Gilead Clinical Trials Website