Tenofovir DF With or Without Peginterferon for Chronic Hepatitis B
- There are two forms of chronic hepatitis B. The difference between the forms is whether or not a viral protein called hepatitis B e antigen is present in the blood. Standard approaches to treating both forms of chronic hepatitis B involve different drugs. One drug is called peginterferon, another is called tenofovir DF. These drugs are often given separately and used for different forms of the disease. However, researchers want to see if combining peginterferon and tenofovir DF will be a more effective treatment than tenofovir DF alone.
- To see whether combining tenofovir DF and peginterferon, or using tenofovir DF alone, is a more effective treatment of chronic hepatitis B.
- Individuals at least 18 years of age who have chronic hepatitis B and are in the Hepatitis B Research Network Cohort study.
- Participants will be screened with a physical exam and medical history. Blood, urine, and liver tissue samples will be collected. Bone and liver imaging studies will also be performed.
- Participants will be divided into two groups. One group will have tenofovir DF alone for 192 weeks (about 4 years). The other group will have tenofovir DF and peginterferon for 24 weeks (about 6 months), and then tenofovir DF alone for 168 weeks (about 3.5 years).
- Participants will take the study drugs on the schedule determined by their study doctors. They will keep a diary to record their doses and any side effects.
- Participants will have three study visits 4 weeks apart after the starting the treatment. At these visits, they will have a physical exam and provide blood samples. They may also provide urine samples and have imaging studies.
- After the first three study visits, participants will continue to have study visits every 12 weeks until the treatment ends at week 192. These visits will have many of the same tests as the first three visits. At some of these visits, they may fill out questionnaires about their quality of life.
- Participants who do not respond to the study drugs may have their medications changed. They may also be asked to stop treatment.
Chronic Hepatitis B e Antigen Negative
Chronic Hepatitis B e Antigen Positive
Drug: Peginterferon and Tenofovir
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Combination Therapy of Pegylated Interferon Alfa-2a and Tenofovir DF Versus Tenofovir DF Monotherapy in HBeAg-Positive and HBeAg-Negative Chronic Hepatitis B|
- HBsAg loss at the end of 48-weeks post-treatment follow-up (week 240) [ Time Frame: 48 weeks post treatment ] [ Designated as safety issue: No ]
- ALT normalization [ Time Frame: 192 weeks; 240 weeks ] [ Designated as safety issue: No ]
- Cumulative HBsAg loss [ Time Frame: 192 weeks; 240 weeks ] [ Designated as safety issue: No ]
- HBsAg seroconversion [ Time Frame: 192 weeks; 240 weeks ] [ Designated as safety issue: No ]
- HBeAg loss [ Time Frame: 192 weels; 240 weeks ] [ Designated as safety issue: No ]
- ALT corresponding to approx 1.25XULN [ Time Frame: 192, 228, 240 weeks ] [ Designated as safety issue: No ]
- HBV DNA & lt; 1000 IU/mL [ Time Frame: 192, 228, 240 weeks ] [ Designated as safety issue: No ]
- HBV DNA & lt; 20 IU/m [ Time Frame: 192, 228, 240 weeks ] [ Designated as safety issue: No ]
- Absence antiviral drug-resistance HBV mu [ Time Frame: 192 weeks ] [ Designated as safety issue: No ]
- Sustained HBV DNA less than 1000 IU/mL [ Time Frame: 192 weeks; 240 weeks ] [ Designated as safety issue: No ]
- Rate treatment discontinuation due to AE [ Time Frame: 192 weeks ] [ Designated as safety issue: Yes ]
- Rates of AE and SAE [ Time Frame: 240 weeks ] [ Designated as safety issue: Yes ]
- HBV DNA & lt; 1000IU/mL & amp; ALT approx 1.25XULN [ Time Frame: 228 and 240 weeks ] [ Designated as safety issue: No ]
- Rate of treatment failure [ Time Frame: 240 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||March 2013|
|Estimated Study Completion Date:||December 2021|
|Estimated Primary Completion Date:||May 2020 (Final data collection date for primary outcome measure)|
Active Comparator: TDF only
Drug: Peginterferon and Tenofovir
This is a randomized (1:1) parallel group design trial comparing (i) tenofovir DF 300 mg daily for 192 weeks (4 years) and (ii) peginterferon alfa-2a 180 micrograms/g 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). A liver biopsy will be obtained at the end-of treatment (week 180-192) to assess improvement in histology. Emtricitabine/tenofovir coformulated as Truvada, approved for treating HIV but not for treating HBV infection, will be offered to participants with primary nonresponse, partial virological response or confirmed virologic breakthrough.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01821794
|Contact: Elenita Rivera, R.N.||(301) firstname.lastname@example.org|
|Contact: Marc G Ghany, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|United States, Minnesota|
|Mayo Clinic, Rochester||Recruiting|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Marc G Ghany, M.D.||National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)|