Chronic Hepatitis B Clinical Trial
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)
Verified date | September 2015 |
Source | Gilead Sciences |
Contact | n/a |
Is FDA regulated | No |
Health authority | United States: Food and Drug Administration |
Study type | Interventional |
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 (HBV).
The study will consist of 2 phases for participants in the TDF+PEG 48 week, TDF 48 week+PEG
16 week, and PEG 48 week 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 with new
signs and/or symptoms will be eligible to receive TDF monotherapy during a retreatment
phase, up to Week 120.
Status | Completed |
Enrollment | 751 |
Est. completion date | July 2015 |
Est. primary completion date | August 2014 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years to 75 Years |
Eligibility |
Inclusion Criteria: - Adults (age 18-75) with chronic HBV (positive for serum hepatitis B surface antigen (HBsAg) or HBV DNA for at least 6 months) prior to baseline - Anti-HBV treatment-naive adults; adults who have taken oral anti-HBV nucleoside therapy with the last dose = 24 weeks prior to screening are also eligible. - Positive or negative for hepatitis B e antigen (HBeAg) - HBV DNA = 20,000 IU/ml (HBeAg-positive participants) and = 2,000 IU/ml (HBeAg-negative participants) - Alanine aminotransferase (ALT) > 54 U/L and = 400 U/L for men and > 36 U/L and = 300 U/L for women - Creatinine clearance = 70 mL/min - Negative serum pregnancy test for females of childbearing potential - Sexually active females of childbearing potential must agree to use a protocol-recommended method of contraception throughout the study and for 30 days following the last dose of study medication - Lactating females must agree to discontinue nursing before initiation of study investigational medicinal product Exclusion Criteria: - Known bridging fibrosis or cirrhosis and/or decompensated liver disease - Evidence of hepatocellular carcinoma - Significant kidney, heart, lung, neurological, autoimmune disease, or bone disease (eg, osteomalacia,chronic osteomyelitis, osteogenesis imperfecta, osteochondrosis, multiple bone fractures) - Absolute neutrophil count < 1,500/mm^3, platelet < 100,000/mm^3, hemoglobin < 10 g/dL (female) or < 11 g/dL (male) - History of severe depression or severe psychiatric disease - Thyroid dysfunction - Coinfection with HIV, hepatitis C virus (HCV) or hepatitis D virus (HDV) - Pregnant |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
Australia | Flinders Medical Center | Adelaide | South Australia |
Australia | Royal Adelaide Hospital | Adelaide SA | South Australia |
Australia | Royal Prince Alfred Hospital | Camperdown | New South Wales |
Australia | Monash Medical Centre | Clayton | Victoria |
Australia | Concord Repatriation General Hospital | Concord | New South Wales |
Australia | Saint Vincents Hospital | Fitzroy | Victoria |
Australia | Western Hospital | Footscray | Victoria |
Australia | Fremantle Hospital | Fremantle | |
Australia | Austin Health | Heidelberg | Victoria |
Australia | Royal Brisbane & Women's Hospital | Herston | Queensland |
Australia | Saint George's Hospital | Kogarah | New South Wales |
Australia | Liverpool Hospital,Gastroenterology Department | Liverpool | New South Wales |
Australia | Alfred Hospital | Melbourne | Victoria |
Australia | Box Hill Hospital | Melbourne | Victoria |
Australia | Sir Charles Gairdner Hospital | Nedlands | |
Australia | Royal Melbourne Hospital | Parkville | Victoria |
Australia | Royal Perth Hospital | Perth | |
Australia | Westmead Hospital | Westmead | New South Wales |
Australia | Princess Alexandra Hospital | Woolloongabba | Queensland |
Canada | Heritage Med Research Clinic, Univ of Calgary | Calgary | Alberta |
Canada | The Ottawa Hospital,Division of Infectious Diseases | Ottawa | Ontario |
Canada | Toronto General Hospital | Toronto | Ontario |
Canada | Toronto Liver Centre | Toronto | Ontario |
Canada | Gastrointestional Research Institute | Vancouver | British Columbia |
Canada | Gordon & Leslie Diamond Health Care Centre | Vancouver | British Columbia |
Canada | Liver and Intestinal Research Centre | Vancouver | British Columbia |
Canada | University of Alberta, Zeidler Ledcore Centre | Zeidler Ledcore Centre | Alberta |
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 | |
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 | Johannes Gutenberg-Universitat Mainz, | Mainz | Rheinland-pfalz |
Greece | Ippokratio Hospital Athens | Attica | |
Greece | General University Hospital of Patras | Patra | |
Greece | Hippokration General Hospital of Thessaloniki | Thessaloniki | |
Greece | Ippokratio Hospital Salonica | Thessaloniki | Attica |
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 | |
India | Vedanta Institute of Medical Sciences | Ahmedabad | Gujarat |
India | Manipal Hospitals | Bangalore | Karnataka |
India | VGM Hospital | Coimbatore | Tamil Nadu |
India | All India Institute of Medical Sciences, Ansari Nagar | Delhi | New Delhi |
India | Institute of digestive and liver disease, Dispur Hospital Ganeshguri | Guwahati | Assam |
India | Global Hospital, Lakdi Ka Pul | Hyderabad | Andhra Pradesh |
India | Institute of Post Graduate Medical Education And Research | Kolkata | West Bengal |
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 | Institute of Liver and Biliary Sciences | New Delhi | |
India | Dharamasi Hospital,Chandni Chowk, South Shivajinagar, | Sangli | Maharashtra |
India | Liver Clinic | Surat | Gujarat |
Italy | Fondazione IRCCS Ca Granda - Ospedale Maggiore Policlinico | Milano | |
Italy | Ospedale San Raffaele | Milano | |
Italy | Azienda Ospedaliero-Universitaria di Cagliari | Monserrato | Cagliari |
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 | |
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 | Inje University Busan Paik Hospital | Busan | |
Korea, Republic of | Pusan National University Hospital | Busan | Gyeongsang |
Korea, Republic of | SoonChunHyang University Hospital Cheonan | Cheonan | Chungcheon |
Korea, Republic of | Kyungpook National University Hospital | Daegu | Gyeongsang |
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 | Korea University Guro Hospital | Seoul | Gyeonggi-d |
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 | CHA Bundang Medical Center, CHA University | Sungnam | Gyeonggi-d |
Korea, Republic of | Yonsei Unversity Wonju College of Medicine Wonju Christian Hospital | Wonju | Gangwon-do |
Korea, Republic of | Pusan National University Yangsan Hospital | Yangsan | Gyeongsang |
Netherlands | Academisch Medisch Centrum | Amsterdam | |
Netherlands | Vrije Universiteit Medisch Centrum | Amsterdam | |
Netherlands | Erasmus Medisch Centrum | Rotterdam | |
Poland | Wojewodzki Szpital Specjalistyczny Kazimierza Dluskeigo w Bialymstoku | Bialystok | |
Poland | Wojewódzki Szpital Obserwacyjno Zakazny im. Tadeusza Browicza | Bydgoszcz | |
Poland | Szpital Specjalistyczny w Chorzowie | Chorzów | Slaskie |
Poland | Szpital Uniwersytecki w Krakowie | Krakow | |
Poland | Wojewódzki Specjalistyczny Szpital im. Dr Wladyslawa Bieganskiego w Lodzi | Lodz | |
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 | SP ZOZ Wojewodzki Szpital Zakazny | Warszawa | |
Portugal | Hospital de Egas Moniz | Lisboa | |
Portugal | Hospital de Santa Maria | Lisboa | |
Portugal | Centro Hospitalar do Porto | Porto | |
Portugal | Hospital São João | Porto | |
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 | |
Singapore | Changi General Hospital | Singapore | |
Singapore | National University Hospital Singapore | Singapore | |
Singapore | Singapore General Hospital | Singapore | |
Singapore | Tan Tock Seng Hospital | Singapore | |
Spain | Hospital General Universitari Vall d' Hebron | Barcelona | |
Spain | Hospital Carlos III | Madrid | |
Spain | Hospital Universitario de La Princesa | Madrid | |
Spain | Hospital Virgen de la Victoria | Malaga | |
Spain | Hospital Universitario Virgen del Rocio | Sevilla | |
Spain | Hospital Meixoeiro | Vigo, Pontevedra | |
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 | Far-Eastern Memorial Hosp | New Taipei City | Banciao Dist |
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 | Chang Gung Medical Foundation.LinKou Branch | Tao-Yuan | Taoyuan |
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 | |
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 States | Digestive Disease Associates | Baltimore | Maryland |
United States | Tufts Medical Center | Boston | Massachusetts |
United States | University of Chicago | Chicago | Illinois |
United States | Avail Clinical Research, LLC | Deland | Florida |
United States | Henry Ford Hospital | Detroit | Michigan |
United States | Medical Procare, PLLC | Flushing | New York |
United States | North Shore University Hospital | Great Neck | New York |
United States | ID Care, Inc. | Hillsborough | New Jersey |
United States | Advanced Liver Therapies at St. Luke's Episcopal Hospital | Houston | Texas |
United States | Kelsey Research Foundation | Houston | Texas |
United States | Liver Associates of Texas, | Houston | Texas |
United States | Asian Pacific Liver Center | Los Angeles | California |
United States | Centre for Advanced Gastroenterology | Maitland | Florida |
United States | University of Miami / Jackson Memorial Medical Center | Miami | Florida |
United States | LSU Gastroenterology/Center for Digestive Diseases | New Orleans | Louisiana |
United States | Tulane University Hospital and Clinic | New Orleans | Louisiana |
United States | Beth Israel Medical Center | New York | New York |
United States | New York Univ. Medical Center | New York | New York |
United States | Weill Cornell Medical College of Cornell University | New York | New York |
United States | Stanford University Medical Center | Palo Alto | California |
United States | Private Practice | Philadelphia | Pennsylvania |
United States | Liver Institute of Virginia, Bon Secours Health System | Richmond | Virginia |
United States | McGuire Research Institute | Richmond | Virginia |
United States | University of Utah | Salt Lake City | Utah |
United States | Research and Education Inc | San Diego | California |
United States | San Jose Gastroenterology | San Jose | California |
Lead Sponsor | Collaborator |
---|---|
Gilead Sciences |
United States, Australia, Canada, France, Germany, Greece, Hong Kong, India, Italy, Korea, Republic of, Netherlands, Poland, Portugal, Romania, Singapore, Spain, Taiwan, Turkey, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Percentage 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 | 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 study Days 491 (Week 70) through 546 (Week 78), so results up to Week 78 are included in this analysis. |
Baseline; Week 72 | No |
Secondary | Percentage 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 | 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 study Days 491 (Week 70) through 546 (Week 78), so results up to Week 78 are included in this analysis. |
Baseline; Week 72 | No |
Secondary | Percentage of Participants With HBsAg Seroconversion at Week 72 | 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 study Days 491 (Week 70) through 546 (Week 78), so results up to Week 78 are included in this analysis. |
Baseline; Week 72 | No |
Secondary | Percentage of Participants With HBeAg Loss and Seroconversion at 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 48 week, TDF 48 week+PEG 16 week, and PEG 48 week 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. |
Baseline; Week 72 | No |
Secondary | Percentage of Participants With Virological Response (HBV DNA < 117 IU/mL) at Week 72 | For the TDF+PEG 48 week, TDF 48 week+PEG 16 week, and PEG 48 week 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. | Week 72 | No |
Secondary | Percentage of Participants With Normal ALT at 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 48 week, TDF 48 week+PEG 16 week, and PEG 48 week 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. |
Week 72 | No |
Secondary | Percentage of Participants Who Required Retreatment | Participants in the TDF 120 week group were not eligible to enter the retreatment phase and are not presented. | Up to 120 weeks | No |
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