Efficacy and Safety of Tenofovir Disoproxil Fumarate (TDF) in Combination With Peginterferon α-2a vs Standard of Care Tenofovir Disoproxil Fumarate Monotherapy or Peginterferon α-2a Monotherapy for 48 Weeks in Chronic Hepatitis B(CHB). (TDF PEG CHB)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01277601
First received: January 13, 2011
Last updated: April 29, 2015
Last verified: April 2015
  Purpose

This study will evaluate the safety and efficacy of tenofovir disoproxil fumarate (TDF) plus peginterferon α-2a (PEG) combination therapy versus standard of care TDF monotherapy or PEG monotherapy in non-cirrhotic adults with chronic hepatitis B virus.


Condition Intervention Phase
Chronic Hepatitis B
Drug: TDF
Drug: PEG
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Proportion of participants with HBsAg loss at Week 72 following treatment with 48 weeks of TDF plus PEG combination versus PEG alone for 48 weeks or TDF alone [ Time Frame: Week 72 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of participants with HBsAg loss at Week 72 following treatment with TDF (48 weeks) plus PEG (16 weeks) combination versus PEG alone for 48 weeks or TDF alone [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
  • Proportion of participants who experience HBsAg loss at Week 96 and Week 120 [ Time Frame: Weeks 96 and 120 ] [ Designated as safety issue: No ]
  • Proportion of participants with virological response (hepatitis B virus [HBV] DNA level < 117 IU/mL) at Weeks 72, 96, and 120 [ Time Frame: Weeks 72, 96, and 120 ] [ Designated as safety issue: No ]
  • Proportion of participants with serological response (HBeAg loss and seroconversion, and HBsAg seroconversion) at Weeks 72, 96, and 120 [ Time Frame: Weeks 72, 96, and 120 ] [ Designated as safety issue: No ]
  • Proportion of participants who experience biochemical response at Weeks 72, 96, and 120 [ Time Frame: Weeks 72, 96, and 120 ] [ Designated as safety issue: No ]
    Biochemical response is defined as having alanine aminotransferase (ALT) < 30 for males and < 19 for females (based on the American Association for the Study of Liver Diseases [AASLD] 2008 guidelines); ALT < 42 for males and < 32 for females (based on central lab upper limit of the normal range [ULN] for ALT).

  • Proportion of participants who require reinitiation or change of anti-HBV therapy while on therapy or posttreatment [ Time Frame: Up to 120 weeks ] [ Designated as safety issue: No ]

Enrollment: 751
Study Start Date: April 2011
Estimated Study Completion Date: July 2015
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TDF+PEG 48 wk
Participants will receive TDF plus PEG concomitantly for 48 weeks.
Drug: TDF
Tenofovir disoproxil fumarate (TDF) 300 mg tablets administered orally once daily
Other Name: Viread®
Drug: PEG
Peginterferon α-2a (PEG) 180 µg administered via subcutaneous injection once weekly
Other Name: Pegasys®
Experimental: TDF+PEG 16 wk, TDF 32 wk
Participants will receive TDF plus PEG concomitantly for 16 weeks, followed by TDF alone for 32 weeks (total 48 weeks).
Drug: TDF
Tenofovir disoproxil fumarate (TDF) 300 mg tablets administered orally once daily
Other Name: Viread®
Drug: PEG
Peginterferon α-2a (PEG) 180 µg administered via subcutaneous injection once weekly
Other Name: Pegasys®
Active Comparator: TDF 120 wk
Participants will receive TDF continuously through 120 weeks.
Drug: TDF
Tenofovir disoproxil fumarate (TDF) 300 mg tablets administered orally once daily
Other Name: Viread®
Active Comparator: PEG 48 wk
Participants will receive PEG for 48 weeks.
Drug: PEG
Peginterferon α-2a (PEG) 180 µg administered via subcutaneous injection once weekly
Other Name: Pegasys®

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults (aged 18-75) with CHB (positive for serum HBsAg or HBV DNA for at least 6 months) prior to baseline.
  • Anti-HBV treatment naive adults and 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 HBeAg -HBV DNA ≥ 20,000 IU/ml for individuals with HBeAg+ and HBV DNA ≥ 2,000 IU/ml for individuals with HBeAg-
  • 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
  • A negative serum pregnancy test is required for females of childbearing potential
  • All sexually active females of childbearing potential must agree to use a protocol recommended method of contraception during heterosexual intercourse 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 renal, cardiovascular, pulmonary, neurological, autoimmune disease or bone disease (e.g., 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
  • Co-infection with HIV, hepatitis C virus (HCV) or hepatitis D virus (HDV)
  • Pregnant
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01277601

  Hide Study Locations
Locations
United States, California
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
United States, Florida
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
United States, Illinois
University of Chicago
Chicago, Illinois, United States
United States, Louisiana
LSU Gastroenterology/Center for Digestive Diseases
New Orleans, Louisiana, United States
Tulane University Hospital and Clinic
New Orleans, Louisiana, United States
United States, Maryland
Digestive Disease Associates
Baltimore, Maryland, United States
United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States
United States, Michigan
Henry Ford Hospital
Detroit, Michigan, United States
United States, New Jersey
ID Care, Inc.
Hillsborough, New Jersey, United States
United States, New York
Medical Procare, PLLC
Flushing, New York, United States
North Shore University Hospital
Great Neck, New York, United States
Weill Cornell Medical College of Cornell University
New York, New York, United States
New York Univ. Medical Center
New York, New York, United States
Beth Israel Medical Center
New York, New York, United States
United States, Pennsylvania
Private Practice
Philadelphia, Pennsylvania, United States
United States, Texas
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
United States, Utah
University of Utah
Salt Lake City, Utah, United States
United States, Virginia
McGuire Research Institute
Richmond, Virginia, United States
Liver Institute of Virginia, Bon Secours Health System
Richmond, Virginia, United States
Australia, New South Wales
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
Australia, Queensland
Royal Brisbane & Women's Hospital
Herston, Queensland, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia
Australia, South Australia
Flinders Medical Center
Adelaide, South Australia, Australia
Royal Adelaide Hospital
Adelaide SA, South Australia, Australia
Australia, Victoria
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
Australia
Fremantle Hospital
Fremantle, Australia
Sir Charles Gairdner Hospital
Nedlands, Australia
Royal Perth Hospital
Perth, Australia
Canada, Alberta
Heritage Med Research Clinic, Univ of Calgary
Calgary, Alberta, Canada
University of Alberta, Zeidler Ledcore Centre
Zeidler Ledcore Centre, Alberta, Canada
Canada, British Columbia
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
Canada, Ontario
The Ottawa Hospital,Division of Infectious Diseases
Ottawa, Ontario, Canada
Toronto General Hospital
Toronto, Ontario, Canada
Toronto Liver Centre
Toronto, Ontario, Canada
France
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 Cedex 9, 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 Cedex, France
Germany
Johannes Gutenberg-Universitat Mainz,
Mainz, Rheinland-pfalz, Germany
Charite Berlin
Berlin, 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
Hannover, Germany
Universitatsklinik Koln
Köln, Germany
Universitatsklinikum Leipzig
Leipzig, Germany
Greece
Ippokratio Hospital Salonica
Thessaloniki, Attica, Greece
Ippokratio Hospital Athens
Attica, Greece
General University Hospital of Patras
Patra, Greece
Hippokration General Hospital of Thessaloniki
Thessaloniki, Greece
Hong Kong
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
India
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
VGM Hospital
Coimbatore, Tamil Nadu, India
Institute of Post Graduate Medical Education And Research
Kolkata, West Bengal, India
Institute of Liver and Biliary Sciences
New Delhi, India
Italy
Azienda Ospedaliero-Universitaria di Cagliari
Monserrato, Cagliari, Italy
Fondazione IRCCS Ca Granda - Ospedale Maggiore Policlinico
Milano, Italy
Ospedale San Raffaele
Milano, 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
Korea, Republic of
SoonChunHyang University Hospital Cheonan
Cheonan, Chungcheon, Korea, Republic of
Yonsei Unversity Wonju College of Medicine Wonju Christian Hospital
Wonju, Gangwon-do, Korea, Republic of
Korea University Ansan Hospital
Ansan-si, Gyeonggi-d, Korea, Republic of
Bucheon St. Mary's Hospital
Bucheon, Gyeonggi-d, Korea, Republic of
Korea University Guro Hospital
Seoul, Gyeonggi-d, Korea, Republic of
CHA Bundang Medical Center, CHA University
Sungnam, Gyeonggi-d, Korea, Republic of
Pusan National University Hospital
Busan, Gyeongsang, Korea, Republic of
Kyungpook National University Hospital
Daegu, Gyeongsang, Korea, Republic of
Pusan National University Yangsan Hospital
Yangsan, Gyeongsang, Korea, Republic of
Inje University Busan Paik Hospital
Busan, Korea, Republic of
Inje University Ilsan Paik Hospital
Goyang, Gyeonggi-Do, Korea, Republic of
Digestive Disease Cntr, Konkuk Univ Hosp
Kwangjin-gu, Seoul, Korea, Republic of
Asan Medical Center
Seoul, Korea, Republic of
Gangnam Severance Hospital
Seoul, Korea, Republic of
Konkuk University Medical Center
Seoul, Korea, Republic of
Samsung Medical Center
Seoul, Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of
Seoul Saint Mary's Hospital
Seoul, Korea, Republic of
Netherlands
Academisch Medisch Centrum
Amsterdam, Netherlands
Vrije Universiteit Medisch Centrum
Amsterdam, Netherlands
Erasmus Medisch Centrum
Rotterdam, Netherlands
Poland
Wojewódzki Specjalistyczny Szpital im. Dr Wladyslawa Bieganskiego w Lodzi
Lodz, Lodzkie, Poland
Samodzielny Publiczny Szpital Kliniczny 1,Klinika Chorób Zakaznych,ulica Staszica 16
Lublin, Lubelskie, Poland
Szpital Specjalistyczny w Chorzowie
Chorzów, Slaskie, 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
Warszawa, Poland
Portugal
Hospital de Egas Moniz
Lisboa, Portugal
Hospital de Santa Maria
Lisboa, Portugal
Centro Hospitalar do Porto
Porto, Portugal
Hospital São João
Porto, Portugal
Romania
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 de Boli Infectioase si Tropicale "Dr. Victor Babes"
Bucharest, Romania
Spitalul Clinic Colentina
Bucuresti, Romania
Spitalul Clinic Judetean de Urgenta Sibiu
Sibiu, Romania
Cabinet Particular Policlinic Algomed SRL-Gastroenterologie
Timisoara, Romania
Singapore
National University Hospital Singapore
Singapore, Singapore
Changi General Hospital
Singapore, Singapore
Singapore General Hospital
Singapore, Singapore
Tan Tock Seng Hospital
Singapore, Singapore
Spain
Hospital General Universitari Vall d' Hebron
Barcelona, Spain
Hospital Universitario de La Princesa
Madrid, Spain
Hospital Carlos III
Madrid, Spain
Hospital Virgen de la Victoria
Malaga, Spain
Hospital Universitario Virgen del Rocio
Sevilla, Spain
Hospital Meixoeiro
Vigo, Pontevedra, Spain
Taiwan
Far-Eastern Memorial Hosp
New Taipei City, Banciao Dist, Taiwan
Chang Gung Medical Foundation.LinKou Branch
Tao-Yuan, Taoyuan, Taiwan
Changhua Christain Hospital
Changhua, Taiwan
Chiayi Christian Hosp
Chia-Yi, Taiwan
Buddhist Tzu Chi General Hospital
Hualien, Taiwan
Chang Gung Memorial Hospital
Kaohsiung, 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
Turkey
Ankara Üniversitesi Tip Fakültesi
Ankara, Turkey
Hacettepe Üniversitesi Tip Fakültesi
Ankara, Turkey
Gaziantep Üniversitesi Tip Fakültesi, Sahinbey Arastirma ve Uygulama Hastanesi
Gaziantep, Turkey
Istanbul Universitesi Istanbul Tip Fakultesi
Istanbul, Turkey
Mersin Üniversitesi Tip Fakültesi, Saglik Arastirma ve Uygulama Hastanesi
Mersin, Turkey
United Kingdom
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
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Eduardo B Martins, MD, DP Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01277601     History of Changes
Other Study ID Numbers: GS-US-174-0149
Study First Received: January 13, 2011
Last Updated: April 29, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
Chronic Hepatitis B
Hep B
Non cirrhotic
Treatment naive
Tenofovir disoproxil fumarate (TDF)
Peginterferon α-2a (PEG)

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis, Chronic
DNA Virus Infections
Digestive System Diseases
Enterovirus Infections
Hepadnaviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Tenofovir
Tenofovir disoproxil
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2015