Clincosm LogoSign in Get a demo

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

Sponsor
Gilead Sciences (Industry)
Overall Status
Completed
CT.gov ID
NCT01277601
Collaborator
(none)
751
Enrollment
171
Locations
4
Arms
51
Duration (Months)
4.4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.
Condition or Disease Intervention/Treatment Phase
Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
751 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (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)
Study Start Date :
Apr 1, 2011
Actual Primary Completion Date :
Aug 1, 2014
Actual Study Completion Date :
Jul 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: TDF+Peg-IFN 48 Weeks

TDF plus Peg-IFN for 48 weeks

Drug: TDF
TDF 300 mg tablets administered orally once daily
Other Names:
  • Viread®

    • Drug: Peg-IFN
    Peg-IFN 180 µg administered via subcutaneous injection once weekly
    Other Names:
  • Pegasys®

    		•
    Experimental: TDF 48 Weeks + Peg-IFN 16 Weeks

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

    Drug: TDF
    TDF 300 mg tablets administered orally once daily
    Other Names:
  • Viread®

    • Drug: Peg-IFN
    Peg-IFN 180 µg administered via subcutaneous injection once weekly
    Other Names:
  • Pegasys®

    		•
    Active Comparator: TDF 120 Weeks

    TDF monotherapy for 120 weeks

    Drug: TDF
    TDF 300 mg tablets administered orally once daily
    Other Names:
  • Viread®

    		•
    Active Comparator: Peg-IFN 48 Weeks

    Peg-IFN monotherapy for 48 weeks

    Drug: Peg-IFN
    Peg-IFN 180 µg administered via subcutaneous injection once weekly
    Other Names:
  • Pegasys®

    		•

    Outcome Measures

    Primary Outcome Measures

    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 [Baseline; Week 72]

      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.

    Secondary Outcome Measures

    1. 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]

      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.

    2. Percentage of Participants With HBsAg Loss at Weeks 96 and 120 [Baseline; Weeks 96 and 120]

      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 96 comprised study Week 90 through Week 102, so results up to Week 102 are included in this analysis. The analysis visit window for Week 120 comprised study Week 114 through Week 126, so results up to Week 126 are included in this analysis.

    3. Percentage of Participants With HBsAg Seroconversion at Weeks 72, 96, and 120 [Baseline; Weeks 72, 96, and 120]

      HBsAg seroconversion was defined as change of detectable antibody to HBsAg from negative to positive. 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. The analysis visit window for Week 96 comprised Week 90 through Week 102, so results up to Week 102 are included in this analysis. The analysis visit window for Week 120 comprised Week 114 through Week 120.

    4. Percentage of Participants With HBeAg Loss and Seroconversion at Week 72 [Baseline; Week 72]

      Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. HBeAg seroconversion was defined as change of detectable antibody to HBeAg from negative to positive. Percentages were based on the number of subjects with non-missing HBeAg results or missing HBeAg results imputed as failures at each visit. For the TDF+Peg-IFN 48 Weeks, TDF 48 Weeks + Peg-IFN 16 Weeks, and Peg-IFN 48 Weeks groups, data are presented in the "Not Retreated" column for participants who had not entered the retreatment phase by Week 72, and in the "Retreated" column for participants who did enter the retreatment phase by Week 72.

    5. Percentage of Participants With HBeAg Loss and Seroconversion at Week 96 [Baseline; Week 96]

      Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. HBeAg seroconversion was defined as change of detectable antibody to HBeAg from negative to positive. Percentages were based on the number of subjects with non-missing HBeAg results or missing HBeAg results imputed as failures at each visit. For the TDF+Peg-IFN 48 Weeks, TDF 48 Weeks + Peg-IFN 16 Weeks, and Peg-IFN 48 Weeks groups, data are presented in the "Not Retreated" column for participants who had not entered the retreatment phase by Week 96, and in the "Retreated" column for participants who did enter the retreatment phase by Week 96.

    6. Percentage of Participants With HBeAg Loss and Seroconversion at Week 120 [Baseline; Week 120]

      Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. HBeAg seroconversion was defined as change of detectable antibody to HBeAg from negative to positive. Percentages were based on the number of subjects with non-missing HBeAg results or missing HBeAg results imputed as failures at each visit. For the TDF+Peg-IFN 48 Weeks, TDF 48 Weeks + Peg-IFN 16 Weeks, and Peg-IFN 48 Weeks groups, data are presented in the "Not Retreated" column for participants who had not entered the retreatment phase by Week 120, and in the "Retreated" column for participants who did enter the retreatment phase by Week 120.

    7. Percentage of Participants With Virological Response (HBV DNA < 117 IU/mL) at Week 72 [Week 72]

      For the TDF+Peg-IFN 48 Weeks, TDF 48 Weeks + Peg-IFN 16 Weeks, and Peg-IFN 48 Weeks groups, data are presented in the "Not Retreated" column for participants who had not entered the retreatment phase by Week 72, and in the "Retreated" column for participants who did enter the retreatment phase by Week 72.

    8. Percentage of Participants With Virological Response (HBV DNA < 117 IU/mL) at Week 96 [Week 96]

      For the TDF+Peg-IFN 48 Weeks, TDF 48 Weeks + Peg-IFN 16 Weeks, and Peg-IFN 48 Weeks groups, data are presented in the "Not Retreated" column for participants who had not entered the retreatment phase by Week 96, and in the "Retreated" column for participants who did enter the retreatment phase by Week 96.

    9. Percentage of Participants With Virological Response (HBV DNA < 117 IU/mL) at Week 120 [Week 120]

      For the TDF+Peg-IFN 48 Weeks, TDF 48 Weeks + Peg-IFN 16 Weeks, and Peg-IFN 48 Weeks groups, data are presented in the "Not Retreated" column for participants who had not entered the retreatment phase by Week 120, and in the "Retreated" column for participants who did enter the retreatment phase by Week 120.

    10. Percentage of Participants With Normal ALT at Week 72 [Week 72]

      Normal ALT was ≤ 30 U/L for males and ≤ 19 U/L for females (based on the American Association for the Study of Liver Diseases (AASLD) 2008 guidelines), and ≤ 41 U/L for males and ≤ 31 U/L for females (based on central laboratory upper limit of the normal range (ULN) for ALT). For the TDF+Peg-IFN 48 Weeks, TDF 48 Weeks + Peg-IFN 16 Weeks, and Peg-IFN 48 Weeks groups, data are presented in the "Not Retreated" column for participants who had not entered the retreatment phase by Week 72, and in the "Retreated" column for participants who did enter the retreatment phase by Week 72.

    11. Percentage of Participants With Normal ALT at Week 96 [Week 96]

      Normal ALT was ≤ 30 U/L for males and ≤ 19 U/L for females (based on the American Association for the Study of Liver Diseases (AASLD) 2008 guidelines), and ≤ 41 U/L for males and ≤ 31 U/L for females (based on central laboratory upper limit of the normal range (ULN) for ALT). For the TDF+Peg-IFN 48 Weeks, TDF 48 Weeks + Peg-IFN 16 Weeks, and Peg-IFN 48 Weeks groups, data are presented in the "Not Retreated" column for participants who had not entered the retreatment phase by Week 96, and in the "Retreated" column for participants who did enter the retreatment phase by Week 96.

    12. Percentage of Participants With Normal ALT at Week 120 [Week 120]

      Normal ALT was ≤ 30 U/L for males and ≤ 19 U/L for females (based on the American Association for the Study of Liver Diseases (AASLD) 2008 guidelines), and ≤ 41 U/L for males and ≤ 31 U/L for females (based on central laboratory upper limit of the normal range (ULN) for ALT). For the TDF+Peg-IFN 48 Weeks, TDF 48 Weeks + Peg-IFN 16 Weeks, and Peg-IFN 48 Weeks groups, data are presented in the "Not Retreated" column for participants who had not entered the retreatment phase by Week 120, and in the "Retreated" column for participants who did enter the retreatment phase by Week 120.

    13. Percentage of Participants Who Required Retreatment [Up to 120 weeks]

      Participants in the TDF 120 week group were not eligible to enter the retreatment phase and are not presented.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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/mm3, platelet < 100,000/mm3, 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Asian Pacific Liver Center Los Angeles California United States
    2 Stanford University Medical Center Palo Alto California United States
    3 Research and Education Inc San Diego California United States
    4 San Jose Gastroenterology San Jose California United States
    5 Avail Clinical Research, LLC Deland Florida United States
    6 Centre for Advanced Gastroenterology Maitland Florida United States
    7 University of Miami / Jackson Memorial Medical Center Miami Florida United States
    8 University of Chicago Chicago Illinois United States
    9 LSU Gastroenterology/Center for Digestive Diseases New Orleans Louisiana United States
    10 Tulane University Hospital and Clinic New Orleans Louisiana United States
    11 Digestive Disease Associates Baltimore Maryland United States
    12 Tufts Medical Center Boston Massachusetts United States
    13 Henry Ford Hospital Detroit Michigan United States
    14 ID Care, Inc. Hillsborough New Jersey United States
    15 Medical Procare, PLLC Flushing New York United States
    16 North Shore University Hospital Great Neck New York United States
    17 Beth Israel Medical Center New York New York United States
    18 New York Univ. Medical Center New York New York United States
    19 Weill Cornell Medical College of Cornell University New York New York United States
    20 Private Practice Philadelphia Pennsylvania United States
    21 Advanced Liver Therapies at St. Luke's Episcopal Hospital Houston Texas United States
    22 Kelsey Research Foundation Houston Texas United States
    23 Liver Associates of Texas, Houston Texas United States
    24 University of Utah Salt Lake City Utah United States
    25 Liver Institute of Virginia, Bon Secours Health System Richmond Virginia United States
    26 McGuire Research Institute Richmond Virginia United States
    27 Royal Prince Alfred Hospital Camperdown New South Wales Australia
    28 Concord Repatriation General Hospital Concord New South Wales Australia
    29 Saint George's Hospital Kogarah New South Wales Australia
    30 Liverpool Hospital,Gastroenterology Department Liverpool New South Wales Australia
    31 Westmead Hospital Westmead New South Wales Australia
    32 Royal Brisbane & Women's Hospital Herston Queensland Australia
    33 Princess Alexandra Hospital Woolloongabba Queensland Australia
    34 Royal Adelaide Hospital Adelaide SA South Australia Australia
    35 Flinders Medical Center Adelaide South Australia Australia
    36 Monash Medical Centre Clayton Victoria Australia
    37 Saint Vincents Hospital Fitzroy Victoria Australia
    38 Western Hospital Footscray Victoria Australia
    39 Austin Health Heidelberg Victoria Australia
    40 Alfred Hospital Melbourne Victoria Australia
    41 Box Hill Hospital Melbourne Victoria Australia
    42 Royal Melbourne Hospital Parkville Victoria Australia
    43 Fremantle Hospital Fremantle Australia
    44 Sir Charles Gairdner Hospital Nedlands Australia
    45 Royal Perth Hospital Perth Australia
    46 Heritage Med Research Clinic, Univ of Calgary Calgary Alberta Canada
    47 University of Alberta, Zeidler Ledcore Centre Zeidler Ledcore Centre Alberta Canada
    48 Gastrointestional Research Institute Vancouver British Columbia Canada
    49 Gordon & Leslie Diamond Health Care Centre Vancouver British Columbia Canada
    50 Liver and Intestinal Research Centre Vancouver British Columbia Canada
    51 The Ottawa Hospital,Division of Infectious Diseases Ottawa Ontario Canada
    52 Toronto General Hospital Toronto Ontario Canada
    53 Toronto Liver Centre Toronto Ontario Canada
    54 Hôpital Beaujon, Service Hepatologie- Centre Pierre Abrami Clichy Cedex France
    55 Hôpital de la Croix Rousse Lyon Cedex France
    56 Hopital Tenon Paris France
    57 Centre Hospitalier Universitaire de Rennes Rennes Cedex 9 France
    58 Hopital Charles Nicolle Rouen France
    59 Centre Hospitalier Regional et Universitaire de Strasbourg, Hopital Civil Strasbourg France
    60 Centre Hospitalier Universitaire Purpan Toulouse France
    61 Hopital Paul Brousse Villejuif Cedex France
    62 Johannes Gutenberg-Universitat Mainz, Mainz Rheinland-pfalz Germany
    63 Charite Berlin Berlin Germany
    64 Universitätsklinikum Essen - klinikum für Gastroenterolgie und Hepatologie, Essen Germany
    65 Johann-Wolfgang-Goethe Universitat, Frankfurt Germany
    66 Asklepios Westklinikum Hamburg Germany
    67 Medizinische Hochschule Hannover,Hastroenterologie und Hepatologie Hannover Germany
    68 Universitatsklinik Koln Köln Germany
    69 Universitatsklinikum Leipzig Leipzig Germany
    70 Ippokratio Hospital Salonica Thessaloniki Attica Greece
    71 Ippokratio Hospital Athens Attica Greece
    72 General University Hospital of Patras Patra Greece
    73 Hippokration General Hospital of Thessaloniki Thessaloniki Greece
    74 Queen Mary Hospital Hong Kong Hong Kong
    75 Princess Margaret Hospital Kowloon Hong Kong
    76 Prince of Wales Hospital Shatin Hong Kong
    77 Alice Ho Miu Ling Nethersole Hospital Tai Po Hong Kong
    78 Global Hospital, Lakdi Ka Pul Hyderabad Andhra Pradesh India
    79 Institute of digestive and liver disease, Dispur Hospital Ganeshguri Guwahati Assam India
    80 Vedanta Institute of Medical Sciences Ahmedabad Gujarat India
    81 Liver Clinic Surat Gujarat India
    82 Manipal Hospitals Bangalore Karnataka India
    83 Department of Hepatology, Institute of Liver Diseases, HPB Surgery and Transplant, Global Hospital Mumbai Maharashtra India
    84 Seth GS Medical College and KEM Hospital, Acharya Donde Marg,Parel Mumbai Maharashtra India
    85 Midas Institute of Gastroenterology Nagpur Maharashtra India
    86 Dharamasi Hospital,Chandni Chowk, South Shivajinagar, Sangli Maharashtra India
    87 All India Institute of Medical Sciences, Ansari Nagar Delhi New Delhi India
    88 VGM Hospital Coimbatore Tamil Nadu India
    89 Institute of Post Graduate Medical Education And Research Kolkata West Bengal India
    90 Institute of Liver and Biliary Sciences New Delhi India
    91 Azienda Ospedaliero-Universitaria di Cagliari Monserrato Cagliari Italy
    92 Fondazione IRCCS Ca Granda - Ospedale Maggiore Policlinico Milano Italy
    93 Ospedale San Raffaele Milano Italy
    94 Seconda Universita degli Studi di Napoli Napoli Italy
    95 Azienda Ospedaliera di Parma,Department of Infectious Diseases and hepatology Parma Italy
    96 Fondazione PTV - Policlinico Tor Vergata Roma Italy
    97 Policlinico Umberto I Rome Italy
    98 University of Milan,Azienda Ospedaliera San Giovanni, Battista di Torino,Dipartimento di Gastroenterologia Torino Italy
    99 SoonChunHyang University Hospital Cheonan Cheonan Chungcheon Korea, Republic of
    100 Yonsei Unversity Wonju College of Medicine Wonju Christian Hospital Wonju Gangwon-do Korea, Republic of
    101 Korea University Ansan Hospital Ansan-si Gyeonggi-d Korea, Republic of
    102 Bucheon St. Mary's Hospital Bucheon Gyeonggi-d Korea, Republic of
    103 Korea University Guro Hospital Seoul Gyeonggi-d Korea, Republic of
    104 CHA Bundang Medical Center, CHA University Sungnam Gyeonggi-d Korea, Republic of
    105 Pusan National University Hospital Busan Gyeongsang Korea, Republic of
    106 Kyungpook National University Hospital Daegu Gyeongsang Korea, Republic of
    107 Pusan National University Yangsan Hospital Yangsan Gyeongsang Korea, Republic of
    108 Inje University Busan Paik Hospital Busan Korea, Republic of
    109 Inje University Ilsan Paik Hospital Goyang, Gyeonggi-Do Korea, Republic of
    110 Digestive Disease Cntr, Konkuk Univ Hosp Kwangjin-gu, Seoul Korea, Republic of
    111 Asan Medical Center Seoul Korea, Republic of
    112 Gangnam Severance Hospital Seoul Korea, Republic of
    113 Konkuk University Medical Center Seoul Korea, Republic of
    114 Samsung Medical Center Seoul Korea, Republic of
    115 Seoul National University Hospital Seoul Korea, Republic of
    116 Seoul Saint Mary's Hospital Seoul Korea, Republic of
    117 Academisch Medisch Centrum Amsterdam Netherlands
    118 Vrije Universiteit Medisch Centrum Amsterdam Netherlands
    119 Erasmus Medisch Centrum Rotterdam Netherlands
    120 Wojewódzki Specjalistyczny Szpital im. Dr Wladyslawa Bieganskiego w Lodzi Lodz Lodzkie Poland
    121 Samodzielny Publiczny Szpital Kliniczny 1,Klinika Chorób Zakaznych,ulica Staszica 16 Lublin Lubelskie Poland
    122 Szpital Specjalistyczny w Chorzowie Chorzów Slaskie Poland
    123 Wojewodzki Szpital Specjalistyczny Kazimierza Dluskeigo w Bialymstoku Bialystok Poland
    124 Wojewódzki Szpital Obserwacyjno Zakazny im. Tadeusza Browicza Bydgoszcz Poland
    125 Szpital Uniwersytecki w Krakowie Krakow Poland
    126 Wojewódzki Specjalistyczny Szpital im. Dr Wladyslawa Bieganskiego w Lodzi Lodz Poland
    127 SP ZOZ Wojewodzki Szpital Zakazny Warszawa Poland
    128 Hospital de Egas Moniz Lisboa Portugal
    129 Hospital de Santa Maria Lisboa Portugal
    130 Centro Hospitalar do Porto Porto Portugal
    131 Hospital São João Porto Portugal
    132 Neomed Research Brasov Romania
    133 Institutul National de Boli Infectioase "Prof. Dr. Matei Bals" Bucharest Romania
    134 Institutul National de Boli Infectioase Prof.Dr. Matei Bals Bucharest Romania
    135 Spitalul Clinic de Boli Infectioase si Tropicale "Dr. Victor Babes" Bucharest Romania
    136 Spitalul Clinic Colentina Bucuresti Romania
    137 Spitalul Clinic Judetean de Urgenta Sibiu Sibiu Romania
    138 Cabinet Particular Policlinic Algomed SRL-Gastroenterologie Timisoara Romania
    139 Changi General Hospital Singapore Singapore
    140 National University Hospital Singapore Singapore Singapore
    141 Singapore General Hospital Singapore Singapore
    142 Tan Tock Seng Hospital Singapore Singapore
    143 Hospital General Universitari Vall d' Hebron Barcelona Spain
    144 Hospital Carlos III Madrid Spain
    145 Hospital Universitario de La Princesa Madrid Spain
    146 Hospital Virgen de la Victoria Malaga Spain
    147 Hospital Universitario Virgen del Rocio Sevilla Spain
    148 Hospital Meixoeiro Vigo, Pontevedra Spain
    149 Far-Eastern Memorial Hosp New Taipei City Banciao Dist Taiwan
    150 Chang Gung Medical Foundation.LinKou Branch Tao-Yuan Taoyuan Taiwan
    151 Changhua Christain Hospital Changhua Taiwan
    152 Chiayi Christian Hosp Chia-Yi Taiwan
    153 Buddhist Tzu Chi General Hospital Hualien Taiwan
    154 Chang Gung Memorial Hospital Kaohsiung Taiwan
    155 Kaohsiung Medical University Hospital Kaosiung Taiwan
    156 Chang Gung Medical Foundation-Keelung Keelung Town/KEELUNG CITY Taiwan
    157 China Medical University Hospital Taichung Taiwan
    158 Chung Shan Medical University Hospital Taichung Taiwan
    159 Taichung Veterans Genl Hosp Taichung Taiwan
    160 National Cheng Kung University Hospital Tainan Taiwan
    161 Cathay General Hospital Taipei Taiwan
    162 National Taiwan University Hospital Taipei Taiwan
    163 Ankara Üniversitesi Tip Fakültesi Ankara Turkey
    164 Hacettepe Üniversitesi Tip Fakültesi Ankara Turkey
    165 Gaziantep Üniversitesi Tip Fakültesi, Sahinbey Arastirma ve Uygulama Hastanesi Gaziantep Turkey
    166 Istanbul Universitesi Istanbul Tip Fakultesi Istanbul Turkey
    167 Mersin Üniversitesi Tip Fakültesi, Saglik Arastirma ve Uygulama Hastanesi Mersin Turkey
    168 The Queen Elizabeth Hospital Birmingham, WSTMID United Kingdom
    169 Royal Free Hospital Hampstead,London United Kingdom
    170 Barts and The London NHS Trust London United Kingdom
    171 King's College Hospital London United Kingdom

    Sponsors and Collaborators

    • Gilead Sciences

    Investigators

    • Study Director: Belinda Jump, Gilead Sciences

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT01277601
    Other Study ID Numbers:
    • GS-US-174-0149
    • 2010-024586-45
    First Posted:
    Jan 17, 2011
    Last Update Posted:
    Aug 26, 2016
    Last Verified:
    Jul 1, 2016
    Keywords provided by Gilead Sciences
    Chronic Hepatitis B
    Hep B
    Non cirrhotic
    Tenofovir disoproxil fumarate (TDF)
    Peginterferon α-2a (Peg-IFN)
    Additional relevant MeSH terms:
    Hepatitis A
    Hepatitis B
    Hepatitis B, Chronic
    Hepatitis
    Hepatitis, Chronic
    Peginterferon alfa-2a

    Study Results

    Participant Flow

    Recruitment Details Participants were enrolled at study sites in North America, Europe, Asia, and Australia. The first participant was screened on 12 April 2011. The last study visit occurred on 17 July 2015.
    Pre-assignment Detail 1597 participants were screened.
    Arm/Group Title TDF+Peg-IFN 48 Weeks TDF 48 Weeks + Peg-IFN 16 Weeks TDF 120 Weeks Peg-IFN 48 Weeks
    Arm/Group Description Tenofovir disoproxil fumarate (TDF) 300 mg tablet once daily plus peginterferon α-2a (Peg-IFN) 180 µg subcutaneous (s.c.) injection once weekly for 48 weeks TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 16 weeks followed by TDF 300 mg tablet once daily for an additional 32 weeks TDF 300 mg tablet once daily for 120 weeks Peg-IFN 180 µg s.c. injection once weekly for 48 weeks
    Period Title: Overall Study
    STARTED 188 187 190 186
    COMPLETED 151 139 163 150
    NOT COMPLETED 37 48 27 36

    Baseline Characteristics

    Arm/Group Title TDF+Peg-IFN 48 Weeks TDF 48 Weeks + Peg-IFN 16 Week TDF 120 Weeks Peg-IFN 48 Weeks Total
    Arm/Group Description TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 48 weeks TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 16 weeks followed by TDF 300 mg tablet once daily for an additional 32 weeks TDF 300 mg tablet once daily for 120 weeks Peg-IFN 180 µg s.c. injection once weekly for 48 weeks Total of all reporting groups
    Overall Participants 186 184 185 185 740
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    38
    (10.7)
    37
    (9.9)
    36
    (10.8)
    38
    (10.5)
    37
    (10.5)
    Sex: Female, Male (Count of Participants)
    Female
    59
    31.7%
    65
    35.3%
    64
    34.6%
    66
    35.7%
    254
    34.3%
    Male
    127
    68.3%
    119
    64.7%
    121
    65.4%
    119
    64.3%
    486
    65.7%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    4
    2.2%
    4
    2.2%
    3
    1.6%
    7
    3.8%
    18
    2.4%
    Not Hispanic or Latino
    182
    97.8%
    179
    97.3%
    181
    97.8%
    177
    95.7%
    719
    97.2%
    Unknown or Not Reported
    0
    0%
    1
    0.5%
    1
    0.5%
    1
    0.5%
    3
    0.4%
    Race/Ethnicity, Customized (participants) [Number]
    Asian
    142
    76.3%
    134
    72.8%
    141
    76.2%
    137
    74.1%
    554
    74.9%
    Black or African American
    5
    2.7%
    3
    1.6%
    4
    2.2%
    6
    3.2%
    18
    2.4%
    Native Hawaiian or Other Pacific Islander
    2
    1.1%
    0
    0%
    0
    0%
    1
    0.5%
    3
    0.4%
    White
    36
    19.4%
    45
    24.5%
    39
    21.1%
    41
    22.2%
    161
    21.8%
    Other
    1
    0.5%
    2
    1.1%
    1
    0.5%
    0
    0%
    4
    0.5%
    Region of Enrollment (participants) [Number]
    Romania
    12
    6.5%
    15
    8.2%
    13
    7%
    9
    4.9%
    49
    6.6%
    Singapore
    7
    3.8%
    5
    2.7%
    7
    3.8%
    8
    4.3%
    27
    3.6%
    Hong Kong
    25
    13.4%
    24
    13%
    27
    14.6%
    21
    11.4%
    97
    13.1%
    United States
    19
    10.2%
    17
    9.2%
    23
    12.4%
    26
    14.1%
    85
    11.5%
    United Kingdom
    2
    1.1%
    3
    1.6%
    1
    0.5%
    4
    2.2%
    10
    1.4%
    Portugal
    0
    0%
    3
    1.6%
    0
    0%
    0
    0%
    3
    0.4%
    India
    10
    5.4%
    5
    2.7%
    9
    4.9%
    6
    3.2%
    30
    4.1%
    Spain
    3
    1.6%
    3
    1.6%
    3
    1.6%
    5
    2.7%
    14
    1.9%
    Greece
    0
    0%
    3
    1.6%
    2
    1.1%
    4
    2.2%
    9
    1.2%
    Canada
    19
    10.2%
    14
    7.6%
    14
    7.6%
    11
    5.9%
    58
    7.8%
    Netherlands
    2
    1.1%
    1
    0.5%
    0
    0%
    1
    0.5%
    4
    0.5%
    Turkey
    5
    2.7%
    6
    3.3%
    6
    3.2%
    7
    3.8%
    24
    3.2%
    Taiwan
    20
    10.8%
    15
    8.2%
    12
    6.5%
    19
    10.3%
    66
    8.9%
    Korea, Republic of
    34
    18.3%
    38
    20.7%
    38
    20.5%
    35
    18.9%
    145
    19.6%
    Poland
    4
    2.2%
    7
    3.8%
    6
    3.2%
    5
    2.7%
    22
    3%
    Italy
    2
    1.1%
    1
    0.5%
    4
    2.2%
    4
    2.2%
    11
    1.5%
    Australia
    10
    5.4%
    14
    7.6%
    15
    8.1%
    14
    7.6%
    53
    7.2%
    France
    6
    3.2%
    3
    1.6%
    1
    0.5%
    3
    1.6%
    13
    1.8%
    Germany
    6
    3.2%
    7
    3.8%
    4
    2.2%
    3
    1.6%
    20
    2.7%
    Hepatitis B Surface Antigen (HBsAg) (log 10 IU/mL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [log 10 IU/mL]
    3.88
    (0.840)
    3.84
    (0.849)
    3.89
    (0.812)
    3.76
    (0.844)
    3.84
    (0.836)
    Hepatitis B e Antigen (HBeAg) Status (participants) [Number]
    Reactive
    108
    58.1%
    105
    57.1%
    109
    58.9%
    106
    57.3%
    428
    57.8%
    Nonreactive
    78
    41.9%
    79
    42.9%
    76
    41.1%
    79
    42.7%
    312
    42.2%
    Hepatitis B Virus (HBV) DNA (log 10 IU/mL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [log 10 IU/mL]
    7.06
    (1.542)
    7.13
    (1.505)
    7.02
    (1.550)
    6.94
    (1.619)
    7.04
    (1.553)
    HBV Genotype (participants) [Number]
    Genotype A
    17
    9.1%
    16
    8.7%
    14
    7.6%
    14
    7.6%
    61
    8.2%
    Genotype B
    50
    26.9%
    51
    27.7%
    49
    26.5%
    53
    28.6%
    203
    27.4%
    Genotype C
    78
    41.9%
    79
    42.9%
    78
    42.2%
    79
    42.7%
    314
    42.4%
    Genotype D
    39
    21%
    36
    19.6%
    41
    22.2%
    38
    20.5%
    154
    20.8%
    Genotype E-H
    2
    1.1%
    2
    1.1%
    3
    1.6%
    1
    0.5%
    8
    1.1%
    Alanine Aminotransferase (ALT) (U/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [U/L]
    121.2
    (180.82)
    112.2
    (94.44)
    100.9
    (67.65)
    106.6
    (91.51)
    110.3
    (116.94)

    Outcome Measures

    1. Primary Outcome
    Title 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
    Description 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.
    Time Frame Baseline; Week 72

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set: participants who were randomized and received at least 1 dose of study drug. Participants in the TDF+Peg-IFN 48 Weeks, TDF 120 Weeks, and Peg-IFN 48 Weeks groups were analyzed by randomized treatment.
    Arm/Group Title TDF+Peg-IFN 48 Weeks TDF 120 Weeks Peg-IFN 48 Weeks
    Arm/Group Description TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 48 weeks TDF 300 mg tablet once daily for 120 weeks Peg-IFN 180 µg s.c. injection once weekly for 48 weeks
    Measure Participants 186 185 185
    Number [percentage of participants]
    9.05
    4.9%
    0.00
    0%
    2.84
    1.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection TDF+Peg-IFN 48 Weeks, TDF 120 Weeks
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value < 0.001
    Comments Raw p-values comparing treatments were based on a log-rank test stratified by HBeAg status and viral genotype.
    Method Log Rank
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection TDF+Peg-IFN 48 Weeks, Peg-IFN 48 Weeks
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments Raw p-values comparing treatments were based on a log-rank test stratified by HBeAg status and viral genotype.
    Method Log Rank
    Comments
    2. Secondary Outcome
    Title 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
    Description 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.
    Time Frame Baseline; Week 72

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set. Participants in the TDF 48 week + Peg-IFN 16 Weeks, TDF 120 Weeks, and Peg-IFN 48 Weeks groups were analyzed.
    Arm/Group Title TDF 48 Weeks + Peg-IFN 16 Weeks TDF 120 Weeks Peg-IFN 48 Weeks
    Arm/Group Description TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 16 weeks followed by TDF 300 mg tablet once daily for an additional 32 weeks TDF 300 mg tablet once daily for 120 weeks Peg-IFN 180 µg s.c. injection once weekly for 48 weeks
    Measure Participants 184 185 185
    Number [percentage of participants]
    2.83
    1.5%
    0.00
    0%
    2.84
    1.5%
    3. Secondary Outcome
    Title Percentage of Participants With HBsAg Loss at Weeks 96 and 120
    Description 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 96 comprised study Week 90 through Week 102, so results up to Week 102 are included in this analysis. The analysis visit window for Week 120 comprised study Week 114 through Week 126, so results up to Week 126 are included in this analysis.
    Time Frame Baseline; Weeks 96 and 120

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title TDF+Peg-IFN 48 Weeks TDF 48 Weeks + Peg-IFN 16 Weeks TDF 120 Week Peg-IFN 48 Weeks
    Arm/Group Description TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 48 weeks TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 16 weeks followed by TDF 300 mg tablet once daily for an additional 32 weeks TDF 300 mg tablet once daily for 120 weeks Peg-IFN 180 µg s.c. injection once weekly for 48 weeks
    Measure Participants 186 184 185 185
    Week 96
    9.69
    5.2%
    3.49
    1.9%
    0.00
    0%
    2.84
    1.5%
    Week 120
    10.36
    5.6%
    3.49
    1.9%
    0.00
    0%
    3.51
    1.9%
    4. Secondary Outcome
    Title Percentage of Participants With HBsAg Seroconversion at Weeks 72, 96, and 120
    Description HBsAg seroconversion was defined as change of detectable antibody to HBsAg from negative to positive. 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. The analysis visit window for Week 96 comprised Week 90 through Week 102, so results up to Week 102 are included in this analysis. The analysis visit window for Week 120 comprised Week 114 through Week 120.
    Time Frame Baseline; Weeks 72, 96, and 120

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title TDF+Peg-IFN 48 Weeks TDF 48 Weeks + Peg-IFN 16 Weeks TDF 120 Weeks Peg-IFN 48 Weeks
    Arm/Group Description TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 48 weeks TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 16 weeks followed by TDF 300 mg tablet once daily for an additional 32 weeks TDF 300 mg tablet once daily for 120 weeks Peg-IFN 180 µg s.c. injection once weekly for 48 weeks
    Measure Participants 186 184 185 185
    Week 72
    8.05
    4.3%
    0.56
    0.3%
    0.00
    0%
    2.87
    1.6%
    Week 96
    8.05
    4.3%
    0.56
    0.3%
    0.00
    0%
    2.87
    1.6%
    Week 120
    10.08
    5.4%
    0.56
    0.3%
    0.00
    0%
    2.87
    1.6%
    5. Secondary Outcome
    Title Percentage of Participants With HBeAg Loss and Seroconversion at Week 72
    Description Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. HBeAg seroconversion was defined as change of detectable antibody to HBeAg from negative to positive. Percentages were based on the number of subjects with non-missing HBeAg results or missing HBeAg results imputed as failures at each visit. For the TDF+Peg-IFN 48 Weeks, TDF 48 Weeks + Peg-IFN 16 Weeks, and Peg-IFN 48 Weeks groups, data are presented in the "Not Retreated" column for participants who had not entered the retreatment phase by Week 72, and in the "Retreated" column for participants who did enter the retreatment phase by Week 72.
    Time Frame Baseline; Week 72

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set who were HBeAg reactive or indeterminate at baseline were analyzed. The missing = failure method was used in which participants on study with missing data were considered to have failed to achieve the outcome.
    Arm/Group Title TDF+Peg-IFN 48 Week (Not Retreated) TDF+Peg-IFN 48 Weeks (Retreated) TDF 48 Weeks + Peg-IFN 16 Week (Not Retreated) TDF 48 Weeks + Peg-IFN 16 Weeks (Retreated) TDF 120 Weeks Peg-IFN 48 Weeks (Not Retreated) Peg-IFN 48 Weeks (Retreated)
    Arm/Group Description TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 48 weeks in the initial treatment phase Following the randomized treatment, participants who met protocol-specified criteria were retreated with TDF 300 mg tablet once daily up to Week 120 in the retreatment phase. TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 16 weeks followed by TDF 300 mg tablet once daily for an additional 32 weeks in the initial treatment phase Following the randomized treatment, participants who met protocol-specified criteria were retreated with TDF 300 mg tablet once daily up to Week 120 in the retreatment phase. TDF 300 mg tablet once daily for 120 weeks. Participants in this group were not eligible to enter the retreatment phase. Peg-IFN 180 µg s.c. injection once weekly for 48 weeks in the initial treatment phase Following the randomized treatment, participants who met protocol-specified criteria were retreated with TDF 300 mg tablet once daily up to Week 120 in the retreatment phase.
    Measure Participants 76 32 61 44 109 64 42
    HBeAg Loss
    35.5
    19.1%
    15.6
    8.5%
    32.8
    17.7%
    15.9
    8.6%
    14.7
    2%
    32.8
    NaN
    14.3
    NaN
    HBeAg Seroconversion
    28.9
    15.5%
    15.6
    8.5%
    31.1
    16.8%
    13.6
    7.4%
    12.8
    1.7%
    31.3
    NaN
    14.3
    NaN
    6. Secondary Outcome
    Title Percentage of Participants With HBeAg Loss and Seroconversion at Week 96
    Description Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. HBeAg seroconversion was defined as change of detectable antibody to HBeAg from negative to positive. Percentages were based on the number of subjects with non-missing HBeAg results or missing HBeAg results imputed as failures at each visit. For the TDF+Peg-IFN 48 Weeks, TDF 48 Weeks + Peg-IFN 16 Weeks, and Peg-IFN 48 Weeks groups, data are presented in the "Not Retreated" column for participants who had not entered the retreatment phase by Week 96, and in the "Retreated" column for participants who did enter the retreatment phase by Week 96.
    Time Frame Baseline; Week 96

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set who were HBeAg reactive or indeterminate at baseline were analyzed. The missing = failure method was used in which participants on study with missing data were considered to have failed to achieve the outcome.
    Arm/Group Title TDF+Peg-IFN 48 Week (Not Retreated) TDF+Peg-IFN 48 Weeks (Retreated) TDF 48 Weeks + Peg-IFN 16 Week (Not Retreated) TDF 48 Weeks + Peg-IFN 16 Weeks (Retreated) TDF 120 Weeks Peg-IFN 48 Weeks (Not Retreated) Peg-IFN 48 Weeks (Retreated)
    Arm/Group Description TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 48 weeks in the initial treatment phase Following the randomized treatment, participants who met protocol-specified criteria were retreated with TDF 300 mg tablet once daily up to Week 120 in the retreatment phase. TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 16 weeks followed by TDF 300 mg tablet once daily for an additional 32 weeks in the initial treatment phase Following the randomized treatment, participants who met protocol-specified criteria were retreated with TDF 300 mg tablet once daily up to Week 120 in the retreatment phase. TDF 300 mg tablet once daily for 120 weeks. Participants in this group were not eligible to enter the retreatment phase. Peg-IFN 180 µg s.c. injection once weekly for 48 weeks in the initial treatment phase Following the randomized treatment, participants who met protocol-specified criteria were retreated with TDF 300 mg tablet once daily up to Week 120 in the retreatment phase.
    Measure Participants 44 64 44 61 109 37 69
    HBeAg Loss
    43.2
    23.2%
    20.3
    11%
    45.5
    24.6%
    14.8
    8%
    18.3
    2.5%
    37.8
    NaN
    14.5
    NaN
    HBeAg Seroconversion
    36.4
    19.6%
    18.8
    10.2%
    43.2
    23.4%
    13.1
    7.1%
    16.5
    2.2%
    29.7
    NaN
    13.0
    NaN
    7. Secondary Outcome
    Title Percentage of Participants With HBeAg Loss and Seroconversion at Week 120
    Description Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. HBeAg seroconversion was defined as change of detectable antibody to HBeAg from negative to positive. Percentages were based on the number of subjects with non-missing HBeAg results or missing HBeAg results imputed as failures at each visit. For the TDF+Peg-IFN 48 Weeks, TDF 48 Weeks + Peg-IFN 16 Weeks, and Peg-IFN 48 Weeks groups, data are presented in the "Not Retreated" column for participants who had not entered the retreatment phase by Week 120, and in the "Retreated" column for participants who did enter the retreatment phase by Week 120.
    Time Frame Baseline; Week 120

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set who were HBeAg reactive or indeterminate at baseline were analyzed. The missing = failure method was used in which participants on study with missing data were considered to have failed to achieve the outcome.
    Arm/Group Title TDF+Peg-IFN 48 Week (Not Retreated) TDF+Peg-IFN 48 Weeks (Retreated) TDF 48 Weeks + Peg-IFN 16 Week (Not Retreated) TDF 48 Weeks + Peg-IFN 16 Weeks (Retreated) TDF 120 Weeks Peg-IFN 48 Weeks (Not Retreated) Peg-IFN 48 Weeks (Retreated)
    Arm/Group Description TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 48 weeks in the initial treatment phase Following the randomized treatment, participants who met protocol-specified criteria were retreated with TDF 300 mg tablet once daily up to Week 120 in the retreatment phase. TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 16 weeks followed by TDF 300 mg tablet once daily for an additional 32 weeks in the initial treatment phase Following the randomized treatment, participants who met protocol-specified criteria were retreated with TDF 300 mg tablet once daily up to Week 120 in the retreatment phase. TDF 300 mg tablet once daily for 120 weeks. Participants in this group were not eligible to enter the retreatment phase. Peg-IFN 180 µg s.c. injection once weekly for 48 weeks in the initial treatment phase Following the randomized treatment, participants who met protocol-specified criteria were retreated with TDF 300 mg tablet once daily up to Week 120 in the retreatment phase.
    Measure Participants 44 64 40 65 109 36 70
    HBeAg Loss
    38.6
    20.8%
    25.0
    13.6%
    37.5
    20.3%
    23.1
    12.5%
    20.2
    2.7%
    33.3
    NaN
    18.6
    NaN
    HBeAg Seroconversion
    29.5
    15.9%
    21.9
    11.9%
    35.0
    18.9%
    15.4
    8.3%
    15.6
    2.1%
    25.0
    NaN
    17.1
    NaN
    8. Secondary Outcome
    Title Percentage of Participants With Virological Response (HBV DNA < 117 IU/mL) at Week 72
    Description For the TDF+Peg-IFN 48 Weeks, TDF 48 Weeks + Peg-IFN 16 Weeks, and Peg-IFN 48 Weeks groups, data are presented in the "Not Retreated" column for participants who had not entered the retreatment phase by Week 72, and in the "Retreated" column for participants who did enter the retreatment phase by Week 72.
    Time Frame Week 72

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set. The missing = failure method was used in which participants on study with missing data were considered to have failed to achieve the endpoint.
    Arm/Group Title TDF+Peg-IFN 48 Weeks (Not Retreated) TDF+Peg-IFN 48 Weeks (Retreated) TDF 48 Weeks + Peg-IFN 16 Weeks (Not Retreated) TDF 48 Weeks + Peg-IFN 16 Weeks (Retreated) TDF 120 Weeks Peg-IFN 48 Weeks (Not Retreated) Peg-IFN 48 Weeks (Retreated)
    Arm/Group Description TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 48 weeks in the initial treatment phase Following the randomized treatment, participants who met protocol-specified criteria were retreated with TDF 300 mg tablet once daily up to Week 120 in the retreatment phase. TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 16 weeks followed by TDF 300 mg tablet once daily for an additional 32 weeks in the initial treatment phase Following the randomized treatment, participants who met protocol-specified criteria were retreated with TDF 300 mg tablet once daily up to Week 120 in the retreatment phase. TDF 300 mg tablet once daily for 120 weeks. Participants in this group were not eligible to enter the retreatment phase. Peg-IFN 180 µg s.c. injection once weekly for 48 weeks in the initial treatment phase Following the randomized treatment, participants who met protocol-specified criteria were retreated with TDF 300 mg tablet once daily up to Week 120 in the retreatment phase.
    Measure Participants 144 42 131 53 185 128 57
    Number [percentage of participants]
    15.3
    8.2%
    26.2
    14.2%
    14.5
    7.8%
    15.1
    8.2%
    84.9
    11.5%
    11.7
    NaN
    40.4
    NaN
    9. Secondary Outcome
    Title Percentage of Participants With Virological Response (HBV DNA < 117 IU/mL) at Week 96
    Description For the TDF+Peg-IFN 48 Weeks, TDF 48 Weeks + Peg-IFN 16 Weeks, and Peg-IFN 48 Weeks groups, data are presented in the "Not Retreated" column for participants who had not entered the retreatment phase by Week 96, and in the "Retreated" column for participants who did enter the retreatment phase by Week 96.
    Time Frame Week 96

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set. The missing = failure method was used in which participants on study with missing data were considered to have failed to achieve the endpoint.
    Arm/Group Title TDF+Peg-IFN 48 Weeks (Not Retreated) TDF+Peg-IFN 48 Weeks (Retreated) TDF 48 Weeks + Peg-IFN 16 Weeks (Not Retreated) TDF 48 Weeks + Peg-IFN 16 Weeks (Retreated) TDF 120 Weeks Peg-IFN 48 Weeks (Not Retreated) Peg-IFN 48 Weeks (Retreated)
    Arm/Group Description TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 48 weeks in the initial treatment phase Following the randomized treatment, participants who met protocol-specified criteria were retreated with TDF 300 mg tablet once daily up to Week 120 in the retreatment phase. TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 16 weeks followed by TDF 300 mg tablet once daily for an additional 32 weeks in the initial treatment phase Following the randomized treatment, participants who met protocol-specified criteria were retreated with TDF 300 mg tablet once daily up to Week 120 in the retreatment phase. TDF 300 mg tablet once daily for 120 weeks. Participants in this group were not eligible to enter the retreatment phase. Peg-IFN 180 µg s.c. injection once weekly for 48 weeks in the initial treatment phase Following the randomized treatment, participants who met protocol-specified criteria were retreated with TDF 300 mg tablet once daily up to Week 120 in the retreatment phase.
    Measure Participants 83 103 83 101 185 72 113
    Number [percentage of participants]
    21.7
    11.7%
    68.0
    37%
    15.7
    8.5%
    80.2
    43.4%
    83.8
    11.3%
    13.9
    NaN
    70.8
    NaN
    10. Secondary Outcome
    Title Percentage of Participants With Virological Response (HBV DNA < 117 IU/mL) at Week 120
    Description For the TDF+Peg-IFN 48 Weeks, TDF 48 Weeks + Peg-IFN 16 Weeks, and Peg-IFN 48 Weeks groups, data are presented in the "Not Retreated" column for participants who had not entered the retreatment phase by Week 120, and in the "Retreated" column for participants who did enter the retreatment phase by Week 120.
    Time Frame Week 120

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set. The missing = failure method was used in which participants on study with missing data were considered to have failed to achieve the endpoint.
    Arm/Group Title TDF+Peg-IFN 48 Weeks (Not Retreated) TDF+Peg-IFN 48 Weeks (Retreated) TDF 48 Weeks + Peg-IFN 16 Weeks (Not Retreated) TDF 48 Weeks + Peg-IFN 16 Weeks (Retreated) TDF 120 Weeks Peg-IFN 48 Weeks (Not Retreated) Peg-IFN 48 Weeks (Retreated)
    Arm/Group Description TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 48 weeks in the initial treatment phase Following the randomized treatment, participants who met protocol-specified criteria were retreated with TDF 300 mg tablet once daily up to Week 120 in the retreatment phase. TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 16 weeks followed by TDF 300 mg tablet once daily for an additional 32 weeks in the initial treatment phase Following the randomized treatment, participants who met protocol-specified criteria were retreated with TDF 300 mg tablet once daily up to Week 120 in the retreatment phase. TDF 300 mg tablet once daily for 120 weeks. Participants in this group were not eligible to enter the retreatment phase. Peg-IFN 180 µg s.c. injection once weekly for 48 weeks in the initial treatment phase Following the randomized treatment, participants who met protocol-specified criteria were retreated with TDF 300 mg tablet once daily up to Week 120 in the retreatment phase.
    Measure Participants 74 112 69 115 185 68 117
    Number [percentage of participants]
    32.4
    17.4%
    81.3
    44.2%
    18.8
    10.2%
    83.5
    45.1%
    82.2
    11.1%
    13.2
    NaN
    82.1
    NaN
    11. Secondary Outcome
    Title Percentage of Participants With Normal ALT at Week 72
    Description Normal ALT was ≤ 30 U/L for males and ≤ 19 U/L for females (based on the American Association for the Study of Liver Diseases (AASLD) 2008 guidelines), and ≤ 41 U/L for males and ≤ 31 U/L for females (based on central laboratory upper limit of the normal range (ULN) for ALT). For the TDF+Peg-IFN 48 Weeks, TDF 48 Weeks + Peg-IFN 16 Weeks, and Peg-IFN 48 Weeks groups, data are presented in the "Not Retreated" column for participants who had not entered the retreatment phase by Week 72, and in the "Retreated" column for participants who did enter the retreatment phase by Week 72.
    Time Frame Week 72

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set. The missing = failure method was used in which participants on study with missing data were considered to have failed to achieve the endpoint.
    Arm/Group Title TDF+Peg-IFN 48 Weeks (Not Retreated) TDF+Peg-IFN 48 Weeks (Retreated) TDF 48 Weeks + Peg-IFN 16 Weeks (Not Retreated) TDF 48 Weeks + Peg-IFN 16 Weeks (Retreated) TDF 120 Weeks Peg-IFN 48 Week (Not Retreated) Peg-IFN 48 Weeks (Retreated)
    Arm/Group Description TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 48 weeks in the initial treatment phase Following the randomized treatment, participants who met protocol-specified criteria were retreated with TDF 300 mg tablet once daily up to Week 120 in the retreatment phase. TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 16 weeks followed by TDF 300 mg tablet once daily for an additional 32 weeks in the initial treatment phase Following the randomized treatment, participants who met protocol-specified criteria were retreated with TDF 300 mg tablet once daily up to Week 120 in the retreatment phase. TDF 300 mg tablet once daily for 120 weeks. Participants in this group were not eligible to enter the retreatment phase. Peg-IFN 180 µg s.c. injection once weekly for 48 weeks in the initial treatment phase Following the randomized treatment, participants who met protocol-specified criteria were retreated with TDF 300 mg tablet once daily up to Week 120 in the retreatment phase.
    Measure Participants 126 60 118 66 185 120 65
    AASLD Criteria
    42.1
    22.6%
    18.3
    9.9%
    40.7
    22%
    18.2
    9.8%
    47.6
    6.4%
    35.0
    NaN
    9.2
    NaN
    Central Laboratory Criteria
    59.5
    32%
    40.0
    21.7%
    57.6
    31.1%
    34.8
    18.8%
    72.4
    9.8%
    57.5
    NaN
    33.8
    NaN
    12. Secondary Outcome
    Title Percentage of Participants With Normal ALT at Week 96
    Description Normal ALT was ≤ 30 U/L for males and ≤ 19 U/L for females (based on the American Association for the Study of Liver Diseases (AASLD) 2008 guidelines), and ≤ 41 U/L for males and ≤ 31 U/L for females (based on central laboratory upper limit of the normal range (ULN) for ALT). For the TDF+Peg-IFN 48 Weeks, TDF 48 Weeks + Peg-IFN 16 Weeks, and Peg-IFN 48 Weeks groups, data are presented in the "Not Retreated" column for participants who had not entered the retreatment phase by Week 96, and in the "Retreated" column for participants who did enter the retreatment phase by Week 96.
    Time Frame Week 96

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set. The missing = failure method was used in which participants on study with missing data were considered to have failed to achieve the endpoint.
    Arm/Group Title TDF+Peg-IFN 48 Weeks (Not Retreated) TDF+Peg-IFN 48 Weeks (Retreated) TDF 48 Weeks + Peg-IFN 16 Weeks (Not Retreated) TDF 48 Weeks + Peg-IFN 16 Weeks (Retreated) TDF 120 Weeks Peg-IFN 48 Week (Not Retreated) Peg-IFN 48 Weeks (Retreated)
    Arm/Group Description TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 48 weeks in the initial treatment phase Following the randomized treatment, participants who met protocol-specified criteria were retreated with TDF 300 mg tablet once daily up to Week 120 in the retreatment phase. TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 16 weeks followed by TDF 300 mg tablet once daily for an additional 32 weeks in the initial treatment phase Following the randomized treatment, participants who met protocol-specified criteria were retreated with TDF 300 mg tablet once daily up to Week 120 in the retreatment phase. TDF 300 mg tablet once daily for 120 weeks. Participants in this group were not eligible to enter the retreatment phase. Peg-IFN 180 µg s.c. injection once weekly for 48 weeks in the initial treatment phase Following the randomized treatment, participants who met protocol-specified criteria were retreated with TDF 300 mg tablet once daily up to Week 120 in the retreatment phase.
    Measure Participants 81 105 82 102 185 72 113
    AASLD Criteria
    43.2
    23.2%
    42.9
    23.3%
    34.1
    18.4%
    46.1
    24.9%
    48.1
    6.5%
    34.7
    NaN
    39.8
    NaN
    Central Laboratory Criteria
    55.6
    29.9%
    71.4
    38.8%
    52.4
    28.3%
    73.5
    39.7%
    73.0
    9.9%
    47.2
    NaN
    68.1
    NaN
    13. Secondary Outcome
    Title Percentage of Participants With Normal ALT at Week 120
    Description Normal ALT was ≤ 30 U/L for males and ≤ 19 U/L for females (based on the American Association for the Study of Liver Diseases (AASLD) 2008 guidelines), and ≤ 41 U/L for males and ≤ 31 U/L for females (based on central laboratory upper limit of the normal range (ULN) for ALT). For the TDF+Peg-IFN 48 Weeks, TDF 48 Weeks + Peg-IFN 16 Weeks, and Peg-IFN 48 Weeks groups, data are presented in the "Not Retreated" column for participants who had not entered the retreatment phase by Week 120, and in the "Retreated" column for participants who did enter the retreatment phase by Week 120.
    Time Frame Week 120

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set. The missing = failure method was used in which participants on study with missing data were considered to have failed to achieve the endpoint.
    Arm/Group Title TDF+Peg-IFN 48 Weeks (Not Retreated) TDF+Peg-IFN 48 Weeks (Retreated) TDF 48 Weeks + Peg-IFN 16 Weeks (Not Retreated) TDF 48 Weeks + Peg-IFN 16 Weeks (Retreated) TDF 120 Weeks Peg-IFN 48 Week (Not Retreated) Peg-IFN 48 Weeks (Retreated)
    Arm/Group Description TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 48 weeks in the initial treatment phase Following the randomized treatment, participants who met protocol-specified criteria were retreated with TDF 300 mg tablet once daily up to Week 120 in the retreatment phase. TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 16 weeks followed by TDF 300 mg tablet once daily for an additional 32 weeks in the initial treatment phase Following the randomized treatment, participants who met protocol-specified criteria were retreated with TDF 300 mg tablet once daily up to Week 120 in the retreatment phase. TDF 300 mg tablet once daily for 120 weeks. Participants in this group were not eligible to enter the retreatment phase. Peg-IFN 180 µg s.c. injection once weekly for 48 weeks in the initial treatment phase Following the randomized treatment, participants who met protocol-specified criteria were retreated with TDF 300 mg tablet once daily up to Week 120 in the retreatment phase.
    Measure Participants 74 112 69 115 185 68 117
    AASLD Criteria
    39.2
    21.1%
    54.5
    29.6%
    30.4
    16.4%
    48.7
    26.3%
    48.6
    6.6%
    30.9
    NaN
    47.0
    NaN
    Central Laboratory Criteria
    44.6
    24%
    72.3
    39.3%
    40.6
    21.9%
    78.3
    42.3%
    73.0
    9.9%
    41.2
    NaN
    73.5
    NaN
    14. Secondary Outcome
    Title Percentage of Participants Who Required Retreatment
    Description Participants in the TDF 120 week group were not eligible to enter the retreatment phase and are not presented.
    Time Frame Up to 120 weeks

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set. Participants in the TDF+Peg-IFN 48 Weeks, TDF 48 Weeks + Peg-IFN 16 Weeks, and Peg-IFN 48 Weeks groups were analyzed.
    Arm/Group Title TDF+Peg-IFN 48 Weeks TDF 48 Weeks + Peg-IFN 16 Weeks Peg-IFN 48 Weeks
    Arm/Group Description TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 48 weeks TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 16 weeks followed by TDF 300 mg tablet once daily for an additional 32 weeks Peg-IFN 180 µg s.c. injection once weekly for 48 weeks
    Measure Participants 186 184 185
    Number [percentage of participants]
    60.2
    32.4%
    62.5
    34%
    63.2
    34.2%

    Adverse Events

    Time Frame Up to 120 weeks plus 30 days
    Adverse Event Reporting Description Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug. Participants were analyzed by actual treatment received.
    Arm/Group Title TDF+Peg-IFN 48 Weeks (Not Retreated) TDF+Peg-IFN 48 Weeks (Retreated) TDF 48 Week + Peg-IFN 16 Weeks (Not Retreated) TDF 48 Weeks + Peg-IFN 16 Weeks (Retreated) TDF 120 Weeks Peg-IFN 48 Weeks (Not Retreated) Peg-IFN 48 Weeks (Retreated)
    Arm/Group Description Adverse events in this reporting group are those occurring in participants who were not retreated or before retreatment through last non-retreatment dose plus 30 days. TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 48 weeks Adverse events in this reporting group are those occurring after TDF retreatment through last TDF retreatment dose plus 30 days. TDF 300 mg tablet once daily up to Week 120 Adverse events in this reporting group are those occurring in participants who were not retreated or before retreatment through last non-retreatment dose plus 30 days. TDF 300 mg tablet once daily plus Peg-IFN 180 µg s.c. injection once weekly for 16 weeks followed by TDF 300 mg tablet once daily for an additional 32 weeks Adverse events in this reporting group are those occurring after TDF retreatment through last TDF retreatment dose plus 30 days. TDF 300 mg tablet once daily up to Week 120 Adverse events in this reporting group are those occurring during the initial treatment phase (up to 120 weeks plus 30 days). TDF 300 mg tablet once daily for up to 120 weeks Adverse events in this reporting group are those occurring in participants who were not retreated or before retreatment through last non-retreatment dose plus 30 days. Peg-IFN 180 µg s.c. injection once weekly for 48 weeks Adverse events in this reporting group are those occurring during the retreatment phase (from start of retreatment up to Week 120 plus 30 days). TDF 300 mg tablet once daily up to Week 120
    All Cause Mortality
    TDF+Peg-IFN 48 Weeks (Not Retreated) TDF+Peg-IFN 48 Weeks (Retreated) TDF 48 Week + Peg-IFN 16 Weeks (Not Retreated) TDF 48 Weeks + Peg-IFN 16 Weeks (Retreated) TDF 120 Weeks Peg-IFN 48 Weeks (Not Retreated) Peg-IFN 48 Weeks (Retreated)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    TDF+Peg-IFN 48 Weeks (Not Retreated) TDF+Peg-IFN 48 Weeks (Retreated) TDF 48 Week + Peg-IFN 16 Weeks (Not Retreated) TDF 48 Weeks + Peg-IFN 16 Weeks (Retreated) TDF 120 Weeks Peg-IFN 48 Weeks (Not Retreated) Peg-IFN 48 Weeks (Retreated)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 21/186 (11.3%) 7/112 (6.3%) 18/184 (9.8%) 3/115 (2.6%) 13/185 (7%) 18/185 (9.7%) 6/117 (5.1%)
    Blood and lymphatic system disorders
    Thrombocytopenia 1/186 (0.5%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 0/117 (0%)
    Cardiac disorders
    Atrial septal defect acquired 0/186 (0%) 0/112 (0%) 1/184 (0.5%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 0/117 (0%)
    Endocrine disorders
    Hyperthyroidism 0/186 (0%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 1/185 (0.5%) 0/185 (0%) 0/117 (0%)
    Gastrointestinal disorders
    Abdominal pain 1/186 (0.5%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 0/117 (0%)
    Haematemesis 0/186 (0%) 0/112 (0%) 1/184 (0.5%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 0/117 (0%)
    Haemorrhoids 1/186 (0.5%) 0/112 (0%) 1/184 (0.5%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 0/117 (0%)
    Intestinal obstruction 0/186 (0%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 1/185 (0.5%) 0/185 (0%) 0/117 (0%)
    Pancreatitis acute 0/186 (0%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 1/185 (0.5%) 0/185 (0%) 0/117 (0%)
    Rectal haemorrhage 0/186 (0%) 0/112 (0%) 1/184 (0.5%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 0/117 (0%)
    Hepatobiliary disorders
    Cholangitis 0/186 (0%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 1/185 (0.5%) 0/185 (0%) 0/117 (0%)
    Cholangitis acute 1/186 (0.5%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 0/117 (0%)
    Cholecystitis chronic 0/186 (0%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 2/185 (1.1%) 0/185 (0%) 0/117 (0%)
    Hepatitis 3/186 (1.6%) 2/112 (1.8%) 4/184 (2.2%) 0/115 (0%) 1/185 (0.5%) 7/185 (3.8%) 1/117 (0.9%)
    Infections and infestations
    Anal abscess 0/186 (0%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 0/185 (0%) 1/185 (0.5%) 0/117 (0%)
    Appendicitis 1/186 (0.5%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 1/185 (0.5%) 1/185 (0.5%) 0/117 (0%)
    Cellulitis 1/186 (0.5%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 0/117 (0%)
    Gastroenteritis 1/186 (0.5%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 0/117 (0%)
    Gastroenteritis viral 0/186 (0%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 1/185 (0.5%) 0/185 (0%) 0/117 (0%)
    Psoas abscess 0/186 (0%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 0/185 (0%) 1/185 (0.5%) 0/117 (0%)
    Sinusitis 1/186 (0.5%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 0/117 (0%)
    Injury, poisoning and procedural complications
    Contusion 0/186 (0%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 1/185 (0.5%) 0/185 (0%) 0/117 (0%)
    Investigations
    Alanine aminotransferase abnormal 1/186 (0.5%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 0/117 (0%)
    Alanine aminotransferase increased 6/186 (3.2%) 3/112 (2.7%) 8/184 (4.3%) 2/115 (1.7%) 1/185 (0.5%) 7/185 (3.8%) 2/117 (1.7%)
    Amylase increased 0/186 (0%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 1/117 (0.9%)
    Aspartate aminotransferase increased 1/186 (0.5%) 2/112 (1.8%) 1/184 (0.5%) 0/115 (0%) 0/185 (0%) 2/185 (1.1%) 1/117 (0.9%)
    Lipase increased 0/186 (0%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 1/117 (0.9%)
    Transaminases increased 0/186 (0%) 0/112 (0%) 1/184 (0.5%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 1/117 (0.9%)
    Metabolism and nutrition disorders
    Cholesterosis 0/186 (0%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 1/117 (0.9%)
    Musculoskeletal and connective tissue disorders
    Exostosis 0/186 (0%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 1/185 (0.5%) 0/185 (0%) 0/117 (0%)
    Rotator cuff syndrome 0/186 (0%) 1/112 (0.9%) 0/184 (0%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 0/117 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of the cervix 0/186 (0%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 1/185 (0.5%) 0/185 (0%) 0/117 (0%)
    B-cell lymphoma 0/186 (0%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 1/185 (0.5%) 0/185 (0%) 0/117 (0%)
    Benign neoplasm of bladder 0/186 (0%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 1/185 (0.5%) 0/185 (0%) 0/117 (0%)
    Brain cancer metastatic 0/186 (0%) 0/112 (0%) 1/184 (0.5%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 0/117 (0%)
    Breast cancer 0/186 (0%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 1/117 (0.9%)
    Cholangiocarcinoma 0/186 (0%) 1/112 (0.9%) 0/184 (0%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 0/117 (0%)
    Gallbladder neoplasm 0/186 (0%) 0/112 (0%) 1/184 (0.5%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 0/117 (0%)
    Haemangioma 0/186 (0%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 1/117 (0.9%)
    Hepatocellular carcinoma 0/186 (0%) 0/112 (0%) 1/184 (0.5%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 1/117 (0.9%)
    Lung neoplasm malignant 0/186 (0%) 0/112 (0%) 1/184 (0.5%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 0/117 (0%)
    Mixed hepatocellular cholangiocarcinoma 0/186 (0%) 1/112 (0.9%) 0/184 (0%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 0/117 (0%)
    Nervous system disorders
    Hepatic encephalopathy 0/186 (0%) 0/112 (0%) 0/184 (0%) 1/115 (0.9%) 0/185 (0%) 0/185 (0%) 0/117 (0%)
    Myelopathy 1/186 (0.5%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 0/117 (0%)
    Neuropathy peripheral 1/186 (0.5%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 0/117 (0%)
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous 1/186 (0.5%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 0/117 (0%)
    Psychiatric disorders
    Anxiety 1/186 (0.5%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 0/117 (0%)
    Depression 1/186 (0.5%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 0/117 (0%)
    Reproductive system and breast disorders
    Prostatitis 0/186 (0%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 0/185 (0%) 1/185 (0.5%) 0/117 (0%)
    Respiratory, thoracic and mediastinal disorders
    Haemoptysis 1/186 (0.5%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 0/185 (0%) 0/185 (0%) 0/117 (0%)
    Skin and subcutaneous tissue disorders
    Rash 0/186 (0%) 0/112 (0%) 0/184 (0%) 0/115 (0%) 0/185 (0%) 1/185 (0.5%) 0/117 (0%)
    Other (Not Including Serious) Adverse Events
    TDF+Peg-IFN 48 Weeks (Not Retreated) TDF+Peg-IFN 48 Weeks (Retreated) TDF 48 Week + Peg-IFN 16 Weeks (Not Retreated) TDF 48 Weeks + Peg-IFN 16 Weeks (Retreated) TDF 120 Weeks Peg-IFN 48 Weeks (Not Retreated) Peg-IFN 48 Weeks (Retreated)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 147/186 (79%) 26/112 (23.2%) 142/184 (77.2%) 31/115 (27%) 89/185 (48.1%) 152/185 (82.2%) 33/117 (28.2%)
    Blood and lymphatic system disorders
    Neutropenia 15/186 (8.1%) 0/112 (0%) 11/184 (6%) 1/115 (0.9%) 0/185 (0%) 15/185 (8.1%) 0/117 (0%)
    Gastrointestinal disorders
    Abdominal pain 7/186 (3.8%) 1/112 (0.9%) 6/184 (3.3%) 1/115 (0.9%) 6/185 (3.2%) 10/185 (5.4%) 1/117 (0.9%)
    Abdominal pain upper 11/186 (5.9%) 2/112 (1.8%) 7/184 (3.8%) 0/115 (0%) 7/185 (3.8%) 6/185 (3.2%) 6/117 (5.1%)
    Diarrhoea 13/186 (7%) 2/112 (1.8%) 10/184 (5.4%) 0/115 (0%) 11/185 (5.9%) 19/185 (10.3%) 4/117 (3.4%)
    Dyspepsia 9/186 (4.8%) 1/112 (0.9%) 6/184 (3.3%) 1/115 (0.9%) 15/185 (8.1%) 9/185 (4.9%) 1/117 (0.9%)
    Nausea 26/186 (14%) 0/112 (0%) 24/184 (13%) 3/115 (2.6%) 11/185 (5.9%) 13/185 (7%) 6/117 (5.1%)
    General disorders
    Asthenia 20/186 (10.8%) 0/112 (0%) 9/184 (4.9%) 1/115 (0.9%) 4/185 (2.2%) 12/185 (6.5%) 1/117 (0.9%)
    Chills 5/186 (2.7%) 0/112 (0%) 13/184 (7.1%) 0/115 (0%) 3/185 (1.6%) 11/185 (5.9%) 1/117 (0.9%)
    Fatigue 40/186 (21.5%) 2/112 (1.8%) 33/184 (17.9%) 4/115 (3.5%) 21/185 (11.4%) 41/185 (22.2%) 6/117 (5.1%)
    Influenza like illness 19/186 (10.2%) 0/112 (0%) 17/184 (9.2%) 0/115 (0%) 10/185 (5.4%) 17/185 (9.2%) 2/117 (1.7%)
    Injection site erythema 12/186 (6.5%) 0/112 (0%) 11/184 (6%) 0/115 (0%) 0/185 (0%) 10/185 (5.4%) 0/117 (0%)
    Malaise 20/186 (10.8%) 0/112 (0%) 12/184 (6.5%) 1/115 (0.9%) 2/185 (1.1%) 7/185 (3.8%) 3/117 (2.6%)
    Pain 8/186 (4.3%) 0/112 (0%) 5/184 (2.7%) 0/115 (0%) 0/185 (0%) 11/185 (5.9%) 2/117 (1.7%)
    Pyrexia 39/186 (21%) 1/112 (0.9%) 36/184 (19.6%) 1/115 (0.9%) 8/185 (4.3%) 43/185 (23.2%) 2/117 (1.7%)
    Infections and infestations
    Nasopharyngitis 5/186 (2.7%) 3/112 (2.7%) 16/184 (8.7%) 3/115 (2.6%) 20/185 (10.8%) 6/185 (3.2%) 3/117 (2.6%)
    Upper respiratory tract infection 10/186 (5.4%) 3/112 (2.7%) 9/184 (4.9%) 9/115 (7.8%) 16/185 (8.6%) 10/185 (5.4%) 5/117 (4.3%)
    Metabolism and nutrition disorders
    Decreased appetite 23/186 (12.4%) 0/112 (0%) 36/184 (19.6%) 2/115 (1.7%) 2/185 (1.1%) 18/185 (9.7%) 0/117 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 9/186 (4.8%) 3/112 (2.7%) 11/184 (6%) 3/115 (2.6%) 4/185 (2.2%) 9/185 (4.9%) 2/117 (1.7%)
    Back pain 16/186 (8.6%) 3/112 (2.7%) 11/184 (6%) 3/115 (2.6%) 11/185 (5.9%) 10/185 (5.4%) 3/117 (2.6%)
    Musculoskeletal pain 5/186 (2.7%) 2/112 (1.8%) 2/184 (1.1%) 1/115 (0.9%) 10/185 (5.4%) 8/185 (4.3%) 1/117 (0.9%)
    Myalgia 29/186 (15.6%) 0/112 (0%) 36/184 (19.6%) 1/115 (0.9%) 2/185 (1.1%) 35/185 (18.9%) 1/117 (0.9%)
    Nervous system disorders
    Dizziness 20/186 (10.8%) 0/112 (0%) 18/184 (9.8%) 1/115 (0.9%) 9/185 (4.9%) 17/185 (9.2%) 4/117 (3.4%)
    Headache 54/186 (29%) 3/112 (2.7%) 37/184 (20.1%) 3/115 (2.6%) 16/185 (8.6%) 52/185 (28.1%) 4/117 (3.4%)
    Psychiatric disorders
    Insomnia 19/186 (10.2%) 3/112 (2.7%) 14/184 (7.6%) 1/115 (0.9%) 6/185 (3.2%) 18/185 (9.7%) 2/117 (1.7%)
    Irritability 11/186 (5.9%) 1/112 (0.9%) 2/184 (1.1%) 0/115 (0%) 0/185 (0%) 11/185 (5.9%) 0/117 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 11/186 (5.9%) 3/112 (2.7%) 9/184 (4.9%) 3/115 (2.6%) 12/185 (6.5%) 16/185 (8.6%) 3/117 (2.6%)
    Oropharyngeal pain 10/186 (5.4%) 3/112 (2.7%) 5/184 (2.7%) 0/115 (0%) 9/185 (4.9%) 11/185 (5.9%) 2/117 (1.7%)
    Skin and subcutaneous tissue disorders
    Alopecia 46/186 (24.7%) 0/112 (0%) 32/184 (17.4%) 1/115 (0.9%) 2/185 (1.1%) 45/185 (24.3%) 1/117 (0.9%)
    Pruritus 14/186 (7.5%) 0/112 (0%) 14/184 (7.6%) 2/115 (1.7%) 4/185 (2.2%) 21/185 (11.4%) 0/117 (0%)
    Rash 20/186 (10.8%) 1/112 (0.9%) 17/184 (9.2%) 1/115 (0.9%) 1/185 (0.5%) 9/185 (4.9%) 2/117 (1.7%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years

    Results Point of Contact

    Name/Title Clinical Trial Disclosures
    Organization Gilead Sciences
    Phone
    Email ClinicalTrialDisclosures@gilead.com
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT01277601
    Other Study ID Numbers:
    • GS-US-174-0149
    • 2010-024586-45
    First Posted:
    Jan 17, 2011
    Last Update Posted:
    Aug 26, 2016
    Last Verified:
    Jul 1, 2016