Combination Therapy of Pegylated Interferon Alfa-2a and Tenofovir Versus Tenofovir Monotherapy in Chronic Hepatitis B
- Conditions
- Hepatitis B
- Interventions
- Drug: Peginterferon-alfa 2a and tenofovir
- Registration Number
- NCT01369212
- Brief Summary
This clinical trial compares the efficacy of peginterferon plus tenofovir for 24 weeks followed by monotherapy with tenofovir for a further 3.5 years to the efficacy of tenofovir alone given for 4 years in patients with chronic hepatitis B. The primary measure of outcome will be HBsAg loss in serum at 48 weeks after stopping all antiviral therapy (sustained off-treatment response).
- Detailed Description
The objective of this study is to compare the long-term efficacy of treatment with combination therapy with peginterferon plus tenofovir versus tenofovir monotherapy in the treatment of chronic hepatitis B.
This is a randomized (1:1) parallel group design trial comparing (i) tenofovir disoproxil fumarate (TDF) 300 mg daily for 192 weeks (4 years) and (ii) peginterferon alfa-2a 180 µg weekly for 24 weeks plus Tenofovir DF 300 mg daily for 192 weeks (4 years). Enrolled participants will be stratified by HBeAg status (positive/negative), genotype (A vs. all others) and cirrhosis (present vs. absent). After 192 weeks of treatment, participants meeting criteria for treatment discontinuation will stop treatment and be followed for 48 weeks (total duration of treatment and follow up is 240 weeks). Emtricitabine/tenofovir coformulated as Truvada, approved for treatment of HIV but not for treatment of hepatitis B virus (HBV) infection, will be offered to patients with primary nonresponse, partial virological response or confirmed virologic breakthrough.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 201
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tenofovir Tenofovir Tenofovir 192 weeks Peginterferon-alfa 2a and tenofovir Peginterferon-alfa 2a and tenofovir A combination of peginterferon-alfa 2a plus tenofovir for 24 weeks and then tenofovir only for 168 weeks
- Primary Outcome Measures
Name Time Method Percent of Participants With Hepatitis B Surface Antigen (HBsAg) Loss by Week 240 Week 240 Estimated percent of participants who became HBsAg negative by week 240 from randomization
- Secondary Outcome Measures
Name Time Method Cumulative Percent of Participants With HBsAg Loss at Week 192 Week 192 Cumulative percentage of participants with HBsAg loss at week 192 estimated using Kaplan-Meier method
Number of Participants With Adverse Events up to 240 weeks Number of participants with at least one adverse event between randomization and week 240
Number of Participants With HBeAg Seroconversion at Week 192 week 192 Number of participants who became HBeAg negative and developed anti-HBe at week 192 among HBeAg positive participants at baseline
Absence of Detectable Antiviral Drug-Resistant HBV Mutations at Week 192 week 192 Absence of detectable antiviral drug-resistant HBV mutations at Week 192
Cumulative Percent of Participants With HBsAg Loss at Week 240 Week 240 Cumulative percent of participants with HBsAg loss at week 240 estimated using Kaplan-Meier method
Number of Participants With Serious Adverse Events Up to 240 weeks Number of participants with at least one serious adverse event between randomization and week 240
Number of Participants With Hepatitis B e Antigen (HBeAg) Loss at Week 192 week 192 Number of participants who became Hepatitis B e antigen (HBeAg) negative at week 192 among HBeAg positive participants at randomization (baseline)
Number of Participants With HBV DNA<1000 IU/mL at Week 240 week 240 Number of participants with HBV DNA \<1000 IU/mL at week 240
Number of Participants With Alanine Transaminase(ALT) Levels <= 38 U/L for Males and <=25 for Females at Week 192 week 192 Number of participants with alanine transaminase(ALT) levels \<= 38 U/L for males and \<=25 for females at week 192. The cut-offs 38 and 25 are approximately 1.25 times the upper limit of normal (30 U/L for males and 20 U/L for females) respectively.
Number of Participants With HBsAg Seroconversion at Week 192 week 192 Number of participants who became with HBsAg negative and developed anti-HBs at week 192
Number of Participants With Normal Alanine Transaminase (ALT) Levels at Week 240 week 240 Number of participants with normal alanine transaminase (ALT) levels \[males ≤30 U/L, for females ≤20 U/L\] at week 240
Number of Participants With HBeAg Loss at Week 240 week 240 Number of participants who became HBeAg negative at week 240 among HBeAg positive participants at baseline
Number of Participants With HBeAg Seroconversion at Week 240 week 240 Number of participants who became HBeAg negative and developed anti-HBe at week 240 among HBeAg positive participants at baseline
Number of Participants With Normal Alanine Transaminase (ALT) Levels at Week 192 week 192 Number of participants with normal alanine transaminase (ALT) levels at week 192 (Normal ALT for males ≤30 U/L, for females ≤20 U/L)
Number of Participants With HBV DNA<1000 IU/mL at Week 192 week 192 Number of participants with HBV DNA \<1000 IU/mL at week 192
Number of Participants With HBsAg Seroconversion at Week 240 week 240 Number of participants who became HBsAg negative and developed anti-HBs at week 240
Number of Participants With HBV DNA<20 IU/mL at Week 192 week 192 Number of participants with HBV DNA\<20 IU/mL at week 192
Number of Participants With HBV DNA<20 IU/mL at Week 240 week 240 Number of participants with HBV DNA\<20 IU/mL at week 240
Trial Locations
- Locations (21)
University of Toronto-Toronto Western Hospital
🇨🇦Toronto, Ontario, Canada
University of California Los Angeles
🇺🇸Los Angeles, California, United States
University of Texas Southwestern
🇺🇸Dallas, Texas, United States
University of Minnesota
🇺🇸Plymouth, Minnesota, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
University of Michigan Health System
🇺🇸Ann Arbor, Michigan, United States
California Pacific Medical Center
🇺🇸San Francisco, California, United States
Cedars Sinai Medical Center
🇺🇸Los Angeles, California, United States
Baylor University Medical Center
🇺🇸Dallas, Texas, United States
University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Queen's Medical Center
🇺🇸Honolulu, Hawaii, United States
NIH Clinical Center
🇺🇸Bethesda, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Saint Louis University
🇺🇸Saint Louis, Missouri, United States
Washington University
🇺🇸Saint Louis, Missouri, United States