Efficacy & Safety of Tenofovir Disoproxil Fumarate (TDF) Plus Peginterferon α-2a (Peg-IFN) Versus TDF or Peg-IFN Monotherapy in Chronic Hepatitis B
- Registration Number
- NCT01277601
- Lead Sponsor
- Gilead Sciences
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 751
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TDF 48 Weeks + Peg-IFN 16 Weeks TDF TDF plus Peg-IFN for 16 weeks, followed by TDF alone for an additional 32 weeks TDF 48 Weeks + Peg-IFN 16 Weeks Peg-IFN TDF plus Peg-IFN for 16 weeks, followed by TDF alone for an additional 32 weeks TDF 120 Weeks TDF TDF monotherapy for 120 weeks Peg-IFN 48 Weeks Peg-IFN Peg-IFN monotherapy for 48 weeks TDF+Peg-IFN 48 Weeks TDF TDF plus Peg-IFN for 48 weeks TDF+Peg-IFN 48 Weeks Peg-IFN TDF plus Peg-IFN for 48 weeks
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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.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.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.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.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.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.
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.
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.
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.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.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.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.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.
Trial Locations
- Locations (170)
Asian Pacific Liver Center
🇺🇸Los Angeles, California, United States
Stanford University Medical Center
🇺🇸Palo Alto, California, United States
Research and Education Inc
🇺🇸San Diego, California, United States
San Jose Gastroenterology
🇺🇸San Jose, California, United States
Avail Clinical Research, LLC
🇺🇸Deland, Florida, United States
Centre for Advanced Gastroenterology
🇺🇸Maitland, Florida, United States
University of Miami / Jackson Memorial Medical Center
🇺🇸Miami, Florida, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
LSU Gastroenterology/Center for Digestive Diseases
🇺🇸New Orleans, Louisiana, United States
Tulane University Hospital and Clinic
🇺🇸New Orleans, Louisiana, United States
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