Efficacy & Safety of Tenofovir Disoproxil Fumarate (TDF) Plus Peginterferon α-2a (Peg-IFN) Versus TDF or Peg-IFN Monotherapy in Chronic Hepatitis B

NCT ID: NCT01277601

Last Updated: 2016-08-26

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

751 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-04-30

Study Completion Date

2015-07-31

Brief Summary

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The primary objective of this study is to evaluate the efficacy of tenofovir disoproxil fumarate (TDF) plus peginterferon α-2a (Peg-IFN) combination therapy for 48 weeks versus standard of care TDF monotherapy or Peg-IFN monotherapy for 48 weeks in non-cirrhotic adults with chronic hepatitis B virus (HBV) as determined by loss of hepatitis B surface antigen (HBsAg).

The study will consist of 2 phases for participants in the TDF+Peg-IFN 48 Weeks, TDF 48 Weeks + Peg-IFN 16 Weeks, and Peg-IFN 48 Weeks groups. Following an initial 48 weeks of treatment, participants in these groups will be monitored for 24 weeks for signs of worsening HBV, and those meeting TDF retreatment and flare management criteria will be eligible to receive TDF monotherapy during a retreatment phase, up to Week 120.

Detailed Description

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Conditions

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Chronic Hepatitis B

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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TDF+Peg-IFN 48 Weeks

TDF plus Peg-IFN for 48 weeks

Group Type EXPERIMENTAL

TDF

Intervention Type DRUG

TDF 300 mg tablets administered orally once daily

Peg-IFN

Intervention Type DRUG

Peg-IFN 180 µg administered via subcutaneous injection once weekly

TDF 48 Weeks + Peg-IFN 16 Weeks

TDF plus Peg-IFN for 16 weeks, followed by TDF alone for an additional 32 weeks

Group Type EXPERIMENTAL

TDF

Intervention Type DRUG

TDF 300 mg tablets administered orally once daily

Peg-IFN

Intervention Type DRUG

Peg-IFN 180 µg administered via subcutaneous injection once weekly

TDF 120 Weeks

TDF monotherapy for 120 weeks

Group Type ACTIVE_COMPARATOR

TDF

Intervention Type DRUG

TDF 300 mg tablets administered orally once daily

Peg-IFN 48 Weeks

Peg-IFN monotherapy for 48 weeks

Group Type ACTIVE_COMPARATOR

Peg-IFN

Intervention Type DRUG

Peg-IFN 180 µg administered via subcutaneous injection once weekly

Interventions

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TDF

TDF 300 mg tablets administered orally once daily

Intervention Type DRUG

Peg-IFN

Peg-IFN 180 µg administered via subcutaneous injection once weekly

Intervention Type DRUG

Other Intervention Names

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Viread® Pegasys®

Eligibility Criteria

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Inclusion Criteria

* Adults (age 18-75) with chronic HBV (positive for serum hepatitis B surface antigen (HBsAg) or HBV DNA for at least 6 months) prior to baseline
* Anti-HBV treatment-naive adults; adults who have taken oral anti-HBV nucleoside therapy with the last dose ≥ 24 weeks prior to screening are also eligible.
* Positive or negative for hepatitis B e antigen (HBeAg)
* HBV DNA ≥ 20,000 IU/ml (HBeAg-positive participants) and ≥ 2,000 IU/ml (HBeAg-negative participants)
* Alanine aminotransferase (ALT) \> 54 U/L and ≤ 400 U/L for men and \> 36 U/L and ≤ 300 U/L for women
* Creatinine clearance ≥ 70 mL/min
* Negative serum pregnancy test for females of childbearing potential
* Sexually active females of childbearing potential must agree to use a protocol-recommended method of contraception throughout the study and for 30 days following the last dose of study medication
* Lactating females must agree to discontinue nursing before initiation of study investigational medicinal product

Exclusion Criteria

* Known bridging fibrosis or cirrhosis and/or decompensated liver disease
* Evidence of hepatocellular carcinoma
* Significant kidney, heart, lung, neurological, autoimmune disease, or bone disease (eg, osteomalacia,chronic osteomyelitis, osteogenesis imperfecta, osteochondrosis, multiple bone fractures)
* Absolute neutrophil count \< 1,500/mm\^3, platelet \< 100,000/mm\^3, hemoglobin \< 10 g/dL (female) or \< 11 g/dL (male)
* History of severe depression or severe psychiatric disease
* Thyroid dysfunction
* Coinfection with HIV, hepatitis C virus (HCV) or hepatitis D virus (HDV)
* Pregnant
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Belinda Jump

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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Asian Pacific Liver Center

Los Angeles, California, United States

Site Status

Stanford University Medical Center

Palo Alto, California, United States

Site Status

Research and Education Inc

San Diego, California, United States

Site Status

San Jose Gastroenterology

San Jose, California, United States

Site Status

Avail Clinical Research, LLC

DeLand, Florida, United States

Site Status

Centre for Advanced Gastroenterology

Maitland, Florida, United States

Site Status

University of Miami / Jackson Memorial Medical Center

Miami, Florida, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

LSU Gastroenterology/Center for Digestive Diseases

New Orleans, Louisiana, United States

Site Status

Tulane University Hospital and Clinic

New Orleans, Louisiana, United States

Site Status

Digestive Disease Associates

Baltimore, Maryland, United States

Site Status

Tufts Medical Center

Boston, Massachusetts, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

ID Care, Inc.

Hillsborough, New Jersey, United States

Site Status

Medical Procare, PLLC

Flushing, New York, United States

Site Status

North Shore University Hospital

Great Neck, New York, United States

Site Status

Beth Israel Medical Center

New York, New York, United States

Site Status

New York Univ. Medical Center

New York, New York, United States

Site Status

Weill Cornell Medical College of Cornell University

New York, New York, United States

Site Status

Private Practice

Philadelphia, Pennsylvania, United States

Site Status

Advanced Liver Therapies at St. Luke's Episcopal Hospital

Houston, Texas, United States

Site Status

Kelsey Research Foundation

Houston, Texas, United States

Site Status

Liver Associates of Texas,

Houston, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

Liver Institute of Virginia, Bon Secours Health System

Richmond, Virginia, United States

Site Status

McGuire Research Institute

Richmond, Virginia, United States

Site Status

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Site Status

Concord Repatriation General Hospital

Concord, New South Wales, Australia

Site Status

Saint George's Hospital

Kogarah, New South Wales, Australia

Site Status

Liverpool Hospital,Gastroenterology Department

Liverpool, New South Wales, Australia

Site Status

Westmead Hospital

Westmead, New South Wales, Australia

Site Status

Royal Brisbane & Women's Hospital

Herston, Queensland, Australia

Site Status

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Site Status

Flinders Medical Center

Adelaide, South Australia, Australia

Site Status

Royal Adelaide Hospital

Adelaide SA, South Australia, Australia

Site Status

Monash Medical Centre

Clayton, Victoria, Australia

Site Status

Saint Vincents Hospital

Fitzroy, Victoria, Australia

Site Status

Western Hospital

Footscray, Victoria, Australia

Site Status

Austin Health

Heidelberg, Victoria, Australia

Site Status

Alfred Hospital

Melbourne, Victoria, Australia

Site Status

Box Hill Hospital

Melbourne, Victoria, Australia

Site Status

Royal Melbourne Hospital

Parkville, Victoria, Australia

Site Status

Fremantle Hospital

Fremantle, , Australia

Site Status

Sir Charles Gairdner Hospital

Nedlands, , Australia

Site Status

Royal Perth Hospital

Perth, , Australia

Site Status

Heritage Med Research Clinic, Univ of Calgary

Calgary, Alberta, Canada

Site Status

University of Alberta, Zeidler Ledcore Centre

Zeidler Ledcore Centre, Alberta, Canada

Site Status

Gastrointestional Research Institute

Vancouver, British Columbia, Canada

Site Status

Gordon & Leslie Diamond Health Care Centre

Vancouver, British Columbia, Canada

Site Status

Liver and Intestinal Research Centre

Vancouver, British Columbia, Canada

Site Status

The Ottawa Hospital,Division of Infectious Diseases

Ottawa, Ontario, Canada

Site Status

Toronto General Hospital

Toronto, Ontario, Canada

Site Status

Toronto Liver Centre

Toronto, Ontario, Canada

Site Status

Hôpital Beaujon, Service Hepatologie- Centre Pierre Abrami

Clichy, Cedex, France

Site Status

Hôpital de la Croix Rousse

Lyon, Cedex, France

Site Status

Hopital Tenon

Paris, , France

Site Status

Centre Hospitalier Universitaire de Rennes

Rennes, , France

Site Status

Hopital Charles Nicolle

Rouen, , France

Site Status

Centre Hospitalier Regional et Universitaire de Strasbourg, Hopital Civil

Strasbourg, , France

Site Status

Centre Hospitalier Universitaire Purpan

Toulouse, , France

Site Status

Hopital Paul Brousse

Villejuif, , France

Site Status

Johannes Gutenberg-Universitat Mainz,

Mainz, Rhineland-Palatinate, Germany

Site Status

Charite Berlin

Berlin, , Germany

Site Status

Universitatsklinik Koln

Cologne, , Germany

Site Status

Universitätsklinikum Essen - klinikum für Gastroenterolgie und Hepatologie,

Essen, , Germany

Site Status

Johann-Wolfgang-Goethe Universitat,

Frankfurt, , Germany

Site Status

Asklepios Westklinikum

Hamburg, , Germany

Site Status

Medizinische Hochschule Hannover,Hastroenterologie und Hepatologie

Hanover, , Germany

Site Status

Universitatsklinikum Leipzig

Leipzig, , Germany

Site Status

Ippokratio Hospital Salonica

Thessaloniki, Attica, Greece

Site Status

Ippokratio Hospital Athens

Attica, , Greece

Site Status

General University Hospital of Patras

Pátrai, , Greece

Site Status

Hippokration General Hospital of Thessaloniki

Thessaloniki, , Greece

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Queen Mary Hospital

Hong Kong, , Hong Kong

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Princess Margaret Hospital

Kowloon, , Hong Kong

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Prince of Wales Hospital

Shatin, , Hong Kong

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Alice Ho Miu Ling Nethersole Hospital

Tai Po, , Hong Kong

Site Status

Global Hospital, Lakdi Ka Pul

Hyderabad, Andhra Pradesh, India

Site Status

Institute of digestive and liver disease, Dispur Hospital Ganeshguri

Guwahati, Assam, India

Site Status

Vedanta Institute of Medical Sciences

Ahmedabad, Gujarat, India

Site Status

Liver Clinic

Surat, Gujarat, India

Site Status

Manipal Hospitals

Bangalore, Karnataka, India

Site Status

Department of Hepatology, Institute of Liver Diseases, HPB Surgery and Transplant, Global Hospital

Mumbai, Maharashtra, India

Site Status

Seth GS Medical College and KEM Hospital, Acharya Donde Marg,Parel

Mumbai, Maharashtra, India

Site Status

Midas Institute of Gastroenterology

Nagpur, Maharashtra, India

Site Status

Dharamasi Hospital,Chandni Chowk, South Shivajinagar,

Sangli, Maharashtra, India

Site Status

All India Institute of Medical Sciences, Ansari Nagar

Delhi, New Delhi, India

Site Status

Institute of Liver and Biliary Sciences

New Delhi, New Delhi, India

Site Status

VGM Hospital

Coimbatore, Tamil Nadu, India

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Institute of Post Graduate Medical Education And Research

Kolkata, West Bengal, India

Site Status

Azienda Ospedaliero-Universitaria di Cagliari

Monserrato, Cagliari, Italy

Site Status

Fondazione IRCCS Ca Granda - Ospedale Maggiore Policlinico

Milan, , Italy

Site Status

Ospedale San Raffaele

Milan, , Italy

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Seconda Universita degli Studi di Napoli

Napoli, , Italy

Site Status

Azienda Ospedaliera di Parma,Department of Infectious Diseases and hepatology

Parma, , Italy

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Fondazione PTV - Policlinico Tor Vergata

Roma, , Italy

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Policlinico Umberto I

Rome, , Italy

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University of Milan,Azienda Ospedaliera San Giovanni, Battista di Torino,Dipartimento di Gastroenterologia

Torino, , Italy

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Academisch Medisch Centrum

Amsterdam, , Netherlands

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Vrije Universiteit Medisch Centrum

Amsterdam, , Netherlands

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Erasmus Medisch Centrum

Rotterdam, , Netherlands

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Samodzielny Publiczny Szpital Kliniczny 1,Klinika Chorób Zakaznych,ulica Staszica 16

Lublin, Lublin Voivodeship, Poland

Site Status

Szpital Specjalistyczny w Chorzowie

Chorzów, Silesian Voivodeship, Poland

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Wojewodzki Szpital Specjalistyczny Kazimierza Dluskeigo w Bialymstoku

Bialystok, , Poland

Site Status

Wojewódzki Szpital Obserwacyjno Zakazny im. Tadeusza Browicza

Bydgoszcz, , Poland

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Szpital Uniwersytecki w Krakowie

Krakow, , Poland

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Wojewódzki Specjalistyczny Szpital im. Dr Wladyslawa Bieganskiego w Lodzi

Lodz, , Poland

Site Status

SP ZOZ Wojewodzki Szpital Zakazny

Warsaw, , Poland

Site Status

Wojewódzki Specjalistyczny Szpital im. Dr Wladyslawa Bieganskiego w Lodzi

Lodz, Łódź Voivodeship, Poland

Site Status

Hospital de Egas Moniz

Lisbon, , Portugal

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Hospital de Santa Maria

Lisbon, , Portugal

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Centro Hospitalar do Porto

Porto, , Portugal

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Hospital São João

Porto, , Portugal

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Neomed Research

Brasov, , Romania

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

Bucharest, , Romania

Site Status

Institutul National de Boli Infectioase Prof.Dr. Matei Bals

Bucharest, , Romania

Site Status

Spitalul Clinic Colentina

Bucharest, , Romania

Site Status

Spitalul Clinic de Boli Infectioase si Tropicale "Dr. Victor Babes"

Bucharest, , Romania

Site Status

Spitalul Clinic Judetean de Urgenta Sibiu

Sibiu, , Romania

Site Status

Cabinet Particular Policlinic Algomed SRL-Gastroenterologie

Timișoara, , Romania

Site Status

Changi General Hospital

Singapore, , Singapore

Site Status

National University Hospital Singapore

Singapore, , Singapore

Site Status

Singapore General Hospital

Singapore, , Singapore

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Tan Tock Seng Hospital

Singapore, , Singapore

Site Status

SoonChunHyang University Hospital Cheonan

Cheonan, Chungcheon, South Korea

Site Status

Yonsei Unversity Wonju College of Medicine Wonju Christian Hospital

Wŏnju, Gangwon-do, South Korea

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Korea University Ansan Hospital

Ansan-si, Gyeonggi-d, South Korea

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Bucheon St. Mary's Hospital

Bucheon-si, Gyeonggi-d, South Korea

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Korea University Guro Hospital

Seoul, Gyeonggi-d, South Korea

Site Status

CHA Bundang Medical Center, CHA University

Sungnam, Gyeonggi-d, South Korea

Site Status

Pusan National University Hospital

Busan, Gyeongsang, South Korea

Site Status

Kyungpook National University Hospital

Daegu, Gyeongsang, South Korea

Site Status

Pusan National University Yangsan Hospital

Yangsan, Gyeongsang, South Korea

Site Status

Inje University Busan Paik Hospital

Busan, , South Korea

Site Status

Inje University Ilsan Paik Hospital

Goyang, Gyeonggi-Do, , South Korea

Site Status

Digestive Disease Cntr, Konkuk Univ Hosp

Kwangjin-gu, Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Gangnam Severance Hospital

Seoul, , South Korea

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Konkuk University Medical Center

Seoul, , South Korea

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Samsung Medical Center

Seoul, , South Korea

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Seoul National University Hospital

Seoul, , South Korea

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Seoul Saint Mary's Hospital

Seoul, , South Korea

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Hospital Universitario de La Princesa

Madrid, Madrid, Spain

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Hospital General Universitari Vall d' Hebron

Barcelona, , Spain

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Hospital Carlos III

Madrid, , Spain

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Hospital Virgen de la Victoria

Málaga, , Spain

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Hospital Universitario Virgen del Rocio

Seville, , Spain

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Hospital Meixoeiro

Vigo, Pontevedra, , Spain

Site Status

Far-Eastern Memorial Hosp

New Taipei City, Banciao Dist, Taiwan

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Chang Gung Medical Foundation.LinKou Branch

Taoyuan District, Taoyuan, Taiwan

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Changhua Christain Hospital

Changhua, , Taiwan

Site Status

Chiayi Christian Hosp

Chiayi City, , Taiwan

Site Status

Buddhist Tzu Chi General Hospital

Hualien City, , Taiwan

Site Status

Chang Gung Memorial Hospital

Kaohsiung City, , Taiwan

Site Status

Kaohsiung Medical University Hospital

Kaosiung, , Taiwan

Site Status

Chang Gung Medical Foundation-Keelung

Keelung Town/KEELUNG CITY, , Taiwan

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China Medical University Hospital

Taichung, , Taiwan

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Chung Shan Medical University Hospital

Taichung, , Taiwan

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Taichung Veterans Genl Hosp

Taichung, , Taiwan

Site Status

National Cheng Kung University Hospital

Tainan City, , Taiwan

Site Status

Cathay General Hospital

Taipei, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Ankara Üniversitesi Tip Fakültesi

Ankara, Ankara, Turkey (Türkiye)

Site Status

Hacettepe Üniversitesi Tip Fakültesi

Ankara, Ankara, Turkey (Türkiye)

Site Status

Gaziantep Üniversitesi Tip Fakültesi, Sahinbey Arastirma ve Uygulama Hastanesi

Gaziantep, , Turkey (Türkiye)

Site Status

Istanbul Universitesi Istanbul Tip Fakultesi

Istanbul, , Turkey (Türkiye)

Site Status

Mersin Üniversitesi Tip Fakültesi, Saglik Arastirma ve Uygulama Hastanesi

Mersin, , Turkey (Türkiye)

Site Status

The Queen Elizabeth Hospital

Birmingham, Wstmid, , United Kingdom

Site Status

Royal Free Hospital

Hampstead,London, , United Kingdom

Site Status

Barts and The London NHS Trust

London, , United Kingdom

Site Status

King's College Hospital

London, , United Kingdom

Site Status

Countries

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United States Australia Canada France Germany Greece Hong Kong India Italy Netherlands Poland Portugal Romania Singapore South Korea Spain Taiwan Turkey (Türkiye) United Kingdom

References

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Marcellin P, Ahn SH, Ma X, Caruntu FA, Tak WY, Elkashab M, Chuang WL, Lim SG, Tabak F, Mehta R, Petersen J, Foster GR, Lou L, Martins EB, Dinh P, Lin L, Corsa A, Charuworn P, Subramanian GM, Reiser H, Reesink HW, Fung S, Strasser SI, Trinh H, Buti M, Gaeta GB, Hui AJ, Papatheodoridis G, Flisiak R, Chan HL; Study 149 Investigators. Combination of Tenofovir Disoproxil Fumarate and Peginterferon alpha-2a Increases Loss of Hepatitis B Surface Antigen in Patients With Chronic Hepatitis B. Gastroenterology. 2016 Jan;150(1):134-144.e10. doi: 10.1053/j.gastro.2015.09.043. Epub 2015 Oct 8.

Reference Type RESULT
PMID: 26453773 (View on PubMed)

Chan HL, Elkhashab M, Trinh H, Tak WY, Ma X, Chuang WL, Kim YJ, Martins EB, Lin L, Dinh P, Charuworn P, Foster GR, Marcellin P. Association of baseline vitamin D levels with clinical parameters and treatment outcomes in chronic hepatitis B. J Hepatol. 2015 Nov;63(5):1086-92. doi: 10.1016/j.jhep.2015.06.025. Epub 2015 Jul 2.

Reference Type RESULT
PMID: 26143444 (View on PubMed)

Other Identifiers

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2010-024586-45

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-174-0149

Identifier Type: -

Identifier Source: org_study_id

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