Efficacy & Safety of Tenofovir Disoproxil Fumarate (TDF) Plus Peginterferon α-2a (Peg-IFN) Versus TDF or Peg-IFN Monotherapy in Chronic Hepatitis B
A Phase 4, Randomized, Open-label, Active-Controlled, Superiority Study to Evaluate the Efficacy and Safety of Tenofovir Disoproxil Fumarate (TDF) in Combination With Peginterferon α-2a (Pegasys®) Versus Standard of Care Tenofovir Disoproxil Fumarate Monotherapy or Peginterferon α-2a Monotherapy for 48 Weeks in Non-Cirrhotic Subjects With HBeAg-Positive or HBeAg-Negative Chronic Hepatitis B (CHB)
2 other identifiers
interventional
751
19 countries
171
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Apr 2011
Longer than P75 for phase_4
171 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 13, 2011
CompletedFirst Posted
Study publicly available on registry
January 17, 2011
CompletedStudy Start
First participant enrolled
April 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2015
CompletedResults Posted
Study results publicly available
September 9, 2015
CompletedAugust 26, 2016
July 1, 2016
3.3 years
January 13, 2011
August 10, 2015
July 15, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Participants With HBsAg Loss at Week 72 Following Treatment With 48 Weeks of TDF Plus Peg-IFN Combination Versus Peg-IFN Alone for 48 Weeks or TDF Alone
Loss of HBsAg was defined as change of detectable HBsAg from positive to negative. Proportions are based on a Kaplan-Meier estimate. The analysis visit window for Week 72 comprised Week 70 through Week 78, so results up to Week 78 are included in this analysis.
Baseline; Week 72
Secondary Outcomes (13)
Percentage of Participants With HBsAg Loss at Week 72 Following Treatment With TDF (48 Weeks) Plus Peg-IFN (16 Weeks) Combination Versus Peg-IFN Alone for 48 Weeks or TDF Alone
Baseline; Week 72
Percentage of Participants With HBsAg Loss at Weeks 96 and 120
Baseline; Weeks 96 and 120
Percentage of Participants With HBsAg Seroconversion at Weeks 72, 96, and 120
Baseline; Weeks 72, 96, and 120
Percentage of Participants With HBeAg Loss and Seroconversion at Week 72
Baseline; Week 72
Percentage of Participants With HBeAg Loss and Seroconversion at Week 96
Baseline; Week 96
- +8 more secondary outcomes
Study Arms (4)
TDF+Peg-IFN 48 Weeks
EXPERIMENTALTDF plus Peg-IFN for 48 weeks
TDF 48 Weeks + Peg-IFN 16 Weeks
EXPERIMENTALTDF plus Peg-IFN for 16 weeks, followed by TDF alone for an additional 32 weeks
TDF 120 Weeks
ACTIVE COMPARATORTDF monotherapy for 120 weeks
Peg-IFN 48 Weeks
ACTIVE COMPARATORPeg-IFN monotherapy for 48 weeks
Interventions
TDF 300 mg tablets administered orally once daily
Peg-IFN 180 µg administered via subcutaneous injection once weekly
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Gilead Scienceslead
Study Sites (171)
Asian Pacific Liver Center
Los Angeles, California, United States
Stanford University Medical Center
Palo Alto, California, United States
Research and Education Inc
San Diego, California, United States
San Jose Gastroenterology
San Jose, California, United States
Avail Clinical Research, LLC
DeLand, Florida, United States
Centre for Advanced Gastroenterology
Maitland, Florida, United States
University of Miami / Jackson Memorial Medical Center
Miami, Florida, United States
University of Chicago
Chicago, Illinois, United States
LSU Gastroenterology/Center for Digestive Diseases
New Orleans, Louisiana, United States
Tulane University Hospital and Clinic
New Orleans, Louisiana, United States
Digestive Disease Associates
Baltimore, Maryland, United States
Tufts Medical Center
Boston, Massachusetts, United States
Henry Ford Hospital
Detroit, Michigan, United States
ID Care, Inc.
Hillsborough, New Jersey, United States
Medical Procare, PLLC
Flushing, New York, United States
North Shore University Hospital
Great Neck, New York, United States
Beth Israel Medical Center
New York, New York, United States
New York Univ. Medical Center
New York, New York, United States
Weill Cornell Medical College of Cornell University
New York, New York, United States
Private Practice
Philadelphia, Pennsylvania, United States
Advanced Liver Therapies at St. Luke's Episcopal Hospital
Houston, Texas, United States
Kelsey Research Foundation
Houston, Texas, United States
Liver Associates of Texas,
Houston, Texas, United States
University of Utah
Salt Lake City, Utah, United States
Liver Institute of Virginia, Bon Secours Health System
Richmond, Virginia, United States
McGuire Research Institute
Richmond, Virginia, United States
Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia
Concord Repatriation General Hospital
Concord, New South Wales, Australia
Saint George's Hospital
Kogarah, New South Wales, Australia
Liverpool Hospital,Gastroenterology Department
Liverpool, New South Wales, Australia
Westmead Hospital
Westmead, New South Wales, Australia
Royal Brisbane & Women's Hospital
Herston, Queensland, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia
Flinders Medical Center
Adelaide, South Australia, Australia
Royal Adelaide Hospital
Adelaide SA, South Australia, Australia
Monash Medical Centre
Clayton, Victoria, Australia
Saint Vincents Hospital
Fitzroy, Victoria, Australia
Western Hospital
Footscray, Victoria, Australia
Austin Health
Heidelberg, Victoria, Australia
Alfred Hospital
Melbourne, Victoria, Australia
Box Hill Hospital
Melbourne, Victoria, Australia
Royal Melbourne Hospital
Parkville, Victoria, Australia
Fremantle Hospital
Fremantle, Australia
Sir Charles Gairdner Hospital
Nedlands, Australia
Royal Perth Hospital
Perth, Australia
Heritage Med Research Clinic, Univ of Calgary
Calgary, Alberta, Canada
University of Alberta, Zeidler Ledcore Centre
Zeidler Ledcore Centre, Alberta, Canada
Gastrointestional Research Institute
Vancouver, British Columbia, Canada
Gordon & Leslie Diamond Health Care Centre
Vancouver, British Columbia, Canada
Liver and Intestinal Research Centre
Vancouver, British Columbia, Canada
The Ottawa Hospital,Division of Infectious Diseases
Ottawa, Ontario, Canada
Toronto General Hospital
Toronto, Ontario, Canada
Toronto Liver Centre
Toronto, Ontario, Canada
Hôpital Beaujon, Service Hepatologie- Centre Pierre Abrami
Clichy, Cedex, France
Hôpital de la Croix Rousse
Lyon, Cedex, France
Hopital Tenon
Paris, France
Centre Hospitalier Universitaire de Rennes
Rennes, France
Hopital Charles Nicolle
Rouen, France
Centre Hospitalier Regional et Universitaire de Strasbourg, Hopital Civil
Strasbourg, France
Centre Hospitalier Universitaire Purpan
Toulouse, France
Hopital Paul Brousse
Villejuif, France
Johannes Gutenberg-Universitat Mainz,
Mainz, Rhineland-Palatinate, Germany
Charite Berlin
Berlin, Germany
Universitatsklinik Koln
Cologne, Germany
Universitätsklinikum Essen - klinikum für Gastroenterolgie und Hepatologie,
Essen, Germany
Johann-Wolfgang-Goethe Universitat,
Frankfurt, Germany
Asklepios Westklinikum
Hamburg, Germany
Medizinische Hochschule Hannover,Hastroenterologie und Hepatologie
Hanover, Germany
Universitatsklinikum Leipzig
Leipzig, Germany
Ippokratio Hospital Salonica
Thessaloniki, Attica, Greece
Ippokratio Hospital Athens
Attica, Greece
General University Hospital of Patras
Pátrai, Greece
Hippokration General Hospital of Thessaloniki
Thessaloniki, Greece
Queen Mary Hospital
Hong Kong, Hong Kong
Princess Margaret Hospital
Kowloon, Hong Kong
Prince of Wales Hospital
Shatin, Hong Kong
Alice Ho Miu Ling Nethersole Hospital
Tai Po, Hong Kong
Global Hospital, Lakdi Ka Pul
Hyderabad, Andhra Pradesh, India
Institute of digestive and liver disease, Dispur Hospital Ganeshguri
Guwahati, Assam, India
Vedanta Institute of Medical Sciences
Ahmedabad, Gujarat, India
Liver Clinic
Surat, Gujarat, India
Manipal Hospitals
Bangalore, Karnataka, India
Department of Hepatology, Institute of Liver Diseases, HPB Surgery and Transplant, Global Hospital
Mumbai, Maharashtra, India
Seth GS Medical College and KEM Hospital, Acharya Donde Marg,Parel
Mumbai, Maharashtra, India
Midas Institute of Gastroenterology
Nagpur, Maharashtra, India
Dharamasi Hospital,Chandni Chowk, South Shivajinagar,
Sangli, Maharashtra, India
All India Institute of Medical Sciences, Ansari Nagar
Delhi, New Delhi, India
Institute of Liver and Biliary Sciences
New Delhi, New Delhi, India
VGM Hospital
Coimbatore, Tamil Nadu, India
Institute of Post Graduate Medical Education And Research
Kolkata, West Bengal, India
Azienda Ospedaliero-Universitaria di Cagliari
Monserrato, Cagliari, Italy
Fondazione IRCCS Ca Granda - Ospedale Maggiore Policlinico
Milan, Italy
Ospedale San Raffaele
Milan, Italy
Seconda Universita degli Studi di Napoli
Napoli, Italy
Azienda Ospedaliera di Parma,Department of Infectious Diseases and hepatology
Parma, Italy
Fondazione PTV - Policlinico Tor Vergata
Roma, Italy
Policlinico Umberto I
Rome, Italy
University of Milan,Azienda Ospedaliera San Giovanni, Battista di Torino,Dipartimento di Gastroenterologia
Torino, Italy
Academisch Medisch Centrum
Amsterdam, Netherlands
Vrije Universiteit Medisch Centrum
Amsterdam, Netherlands
Erasmus Medisch Centrum
Rotterdam, Netherlands
Samodzielny Publiczny Szpital Kliniczny 1,Klinika Chorób Zakaznych,ulica Staszica 16
Lublin, Lublin Voivodeship, Poland
Szpital Specjalistyczny w Chorzowie
Chorzów, Silesian Voivodeship, Poland
Wojewodzki Szpital Specjalistyczny Kazimierza Dluskeigo w Bialymstoku
Bialystok, Poland
Wojewódzki Szpital Obserwacyjno Zakazny im. Tadeusza Browicza
Bydgoszcz, Poland
Szpital Uniwersytecki w Krakowie
Krakow, Poland
Wojewódzki Specjalistyczny Szpital im. Dr Wladyslawa Bieganskiego w Lodzi
Lodz, Poland
SP ZOZ Wojewodzki Szpital Zakazny
Warsaw, Poland
Wojewódzki Specjalistyczny Szpital im. Dr Wladyslawa Bieganskiego w Lodzi
Lodz, Łódź Voivodeship, Poland
Hospital de Egas Moniz
Lisbon, Portugal
Hospital de Santa Maria
Lisbon, Portugal
Centro Hospitalar do Porto
Porto, Portugal
Hospital São João
Porto, Portugal
Neomed Research
Brasov, Romania
Institutul National de Boli Infectioase "Prof. Dr. Matei Bals"
Bucharest, Romania
Institutul National de Boli Infectioase Prof.Dr. Matei Bals
Bucharest, Romania
Spitalul Clinic Colentina
Bucharest, Romania
Spitalul Clinic de Boli Infectioase si Tropicale "Dr. Victor Babes"
Bucharest, Romania
Spitalul Clinic Judetean de Urgenta Sibiu
Sibiu, Romania
Cabinet Particular Policlinic Algomed SRL-Gastroenterologie
Timișoara, Romania
Changi General Hospital
Singapore, Singapore
National University Hospital Singapore
Singapore, Singapore
Singapore General Hospital
Singapore, Singapore
Tan Tock Seng Hospital
Singapore, Singapore
SoonChunHyang University Hospital Cheonan
Cheonan, Chungcheon, South Korea
Yonsei Unversity Wonju College of Medicine Wonju Christian Hospital
Wŏnju, Gangwon-do, South Korea
Korea University Ansan Hospital
Ansan-si, Gyeonggi-d, South Korea
Bucheon St. Mary's Hospital
Bucheon-si, Gyeonggi-d, South Korea
Korea University Guro Hospital
Seoul, Gyeonggi-d, South Korea
CHA Bundang Medical Center, CHA University
Sungnam, Gyeonggi-d, South Korea
Pusan National University Hospital
Busan, Gyeongsang, South Korea
Kyungpook National University Hospital
Daegu, Gyeongsang, South Korea
Pusan National University Yangsan Hospital
Yangsan, Gyeongsang, South Korea
Inje University Busan Paik Hospital
Busan, South Korea
Inje University Ilsan Paik Hospital
Goyang, Gyeonggi-Do, South Korea
Digestive Disease Cntr, Konkuk Univ Hosp
Kwangjin-gu, Seoul, South Korea
Asan Medical Center
Seoul, South Korea
Gangnam Severance Hospital
Seoul, South Korea
Konkuk University Medical Center
Seoul, South Korea
Samsung Medical Center
Seoul, South Korea
Seoul National University Hospital
Seoul, South Korea
Seoul Saint Mary's Hospital
Seoul, South Korea
Hospital Universitario de La Princesa
Madrid, Madrid, Spain
Hospital General Universitari Vall d' Hebron
Barcelona, Spain
Hospital Carlos III
Madrid, Spain
Hospital Virgen de la Victoria
Málaga, Spain
Hospital Universitario Virgen del Rocio
Seville, Spain
Hospital Meixoeiro
Vigo, Pontevedra, Spain
Far-Eastern Memorial Hosp
New Taipei City, Banciao Dist, Taiwan
Chang Gung Medical Foundation.LinKou Branch
Taoyuan District, Taoyuan, Taiwan
Changhua Christain Hospital
Changhua, Taiwan
Chiayi Christian Hosp
Chiayi City, Taiwan
Buddhist Tzu Chi General Hospital
Hualien City, Taiwan
Chang Gung Memorial Hospital
Kaohsiung City, Taiwan
Kaohsiung Medical University Hospital
Kaosiung, Taiwan
Chang Gung Medical Foundation-Keelung
Keelung Town/KEELUNG CITY, Taiwan
China Medical University Hospital
Taichung, Taiwan
Chung Shan Medical University Hospital
Taichung, Taiwan
Taichung Veterans Genl Hosp
Taichung, Taiwan
National Cheng Kung University Hospital
Tainan, Taiwan
Cathay General Hospital
Taipei, Taiwan
National Taiwan University Hospital
Taipei, Taiwan
Ankara Üniversitesi Tip Fakültesi
Ankara, Ankara, Turkey (Türkiye)
Hacettepe Üniversitesi Tip Fakültesi
Ankara, Ankara, Turkey (Türkiye)
Gaziantep Üniversitesi Tip Fakültesi, Sahinbey Arastirma ve Uygulama Hastanesi
Gaziantep, Turkey (Türkiye)
Istanbul Universitesi Istanbul Tip Fakultesi
Istanbul, Turkey (Türkiye)
Mersin Üniversitesi Tip Fakültesi, Saglik Arastirma ve Uygulama Hastanesi
Mersin, Turkey (Türkiye)
The Queen Elizabeth Hospital
Birmingham, Wstmid, United Kingdom
Royal Free Hospital
Hampstead,London, United Kingdom
Barts and The London NHS Trust
London, United Kingdom
King's College Hospital
London, United Kingdom
Related Publications (2)
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.
PMID: 26453773RESULTChan 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.
PMID: 26143444RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Trial Disclosures
- Organization
- Gilead Sciences
Study Officials
- STUDY DIRECTOR
Belinda Jump
Gilead Sciences
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 13, 2011
First Posted
January 17, 2011
Study Start
April 1, 2011
Primary Completion
August 1, 2014
Study Completion
July 1, 2015
Last Updated
August 26, 2016
Results First Posted
September 9, 2015
Record last verified: 2016-07