A Study of Pegylated Interferon Alfa-2a and Lamivudine in Patients With HBeAg-Negative Chronic Hepatitis B Virus (HBV)
- Conditions
- Hepatitis B, Chronic
- Interventions
- Drug: Pegylated interferon (PEG-IFN) alfa-2a, 180 mcgDrug: Pegylated interferon (PEG-IFN) alfa-2a, 135 mcg
- Registration Number
- NCT01095835
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This study will compare the efficacy and safety of 2 different durations of treatment with pegylated interferon (PEG-IFN) alfa-2a in participants with Hepatitis B e Antigen (HBeAg)-negative chronic hepatitis B virus (HBV). It will also compare PEG-IFN alfa 2a treatment alone and in combination with lamivudine (LAM). The anticipated time on study treatment is 1-2 years, and the target sample size is 100-500 individuals.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 131
- adults 18-70 years of age;
- HBeAg-negative chronic hepatitis B for >/=6 months;
- liver disease consistent with chronic hepatitis B.
- interferon-based, systemic anti-HBV, antiviral, anti-neoplastic, or immunomodulatory therapy </=12 months before first dose of study drug;
- non-responders to previous interferon therapy;
- co-infection with hepatitis A, C or D, or with human immunodeficiency virus (HIV);
- hepatocellular cancer;
- compensated (Child A, score 6) or decompensated liver disease (Child B or C).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PEG-IFN+LAM96 Lamivudine (LAM) Treatment with PEG-IFN and lamivudine in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by 48 weeks of only PEG-IFN treatment (total 96 weeks of treatment). PEG-IFN96 Pegylated interferon (PEG-IFN) alfa-2a, 135 mcg Treatment with PEG-IFN in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by another 48 weeks of PEG-IFN treatment (total 96 weeks of treatment). PEG-IFN+LAM96 Pegylated interferon (PEG-IFN) alfa-2a, 180 mcg Treatment with PEG-IFN and lamivudine in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by 48 weeks of only PEG-IFN treatment (total 96 weeks of treatment). PEG-IFN48 Pegylated interferon (PEG-IFN) alfa-2a, 180 mcg Treatment with PEG-IFN in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks. PEG-IFN96 Pegylated interferon (PEG-IFN) alfa-2a, 180 mcg Treatment with PEG-IFN in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by another 48 weeks of PEG-IFN treatment (total 96 weeks of treatment). PEG-IFN+LAM96 Pegylated interferon (PEG-IFN) alfa-2a, 135 mcg Treatment with PEG-IFN and lamivudine in participants with HBeAg-negative chronic hepatitis B virus for 48 weeks followed by 48 weeks of only PEG-IFN treatment (total 96 weeks of treatment).
- Primary Outcome Measures
Name Time Method Percentage of Participants Achieving the Combined Response at the End of the Follow-up Period At the end of the 48-week follow-up period at Week 144 Combined response was defined as alanine aminotransferase (ALT) normalization plus lowering of hepatitis B virus (HBV) deoxyribo nucleic acid (DNA) levels to \<20,000 copies/mL (\<3,400 IU/mL) and was measured at the end of the 48-week follow-up period. Participants with missing 48 weeks follow-up measurements were considered as non-responders. However, if the scheduled 48-weeks post-treatment tests were performed earlier or later than 48 weeks post-treatment, but not earlier than 36 weeks post-treatment, the corresponding results were considered to determine response.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Achieving the Combined Response at 24 Weeks of Follow-up At the end of 24 weeks of follow-up at Week 120 Combined response was defined as ALT normalization plus lowering of HBV-DNA levels to \<20,000 copies/mL (\<3,400 IU/mL). In case of missing week-24 post-treatment measurements, the nearest value with respect to the schedule time point in the time window 12 weeks post treatment until study end was used.
Percentage of Participants Achieving Combined Response Using a Cut-Off for HBV-DNA Levels to 2,000 IU/mL At end of treatment at Week 48 or 96 depending on the study arm, at the end of 24 weeks of follow-up at Week 120 and at the end of the follow-up period at Week 144 Combined response was defined here as ALT normalization plus lowering HBV-DNA levels to a cutt-off \<2,000 IU/mL. In case of missing end of treatment measurements, the next available post-treatment value was used. In case of missing week-24 post-treatment measurements, the nearest value with respect to the schedule time point in the time window 12 weeks post treatment until study end was used. Participants with missing 48 weeks follow-up measurements were considered as non-responders. However, if the scheduled 48-weeks post-treatment tests were performed earlier or later than 48 weeks post-treatment, but not earlier than 36 weeks post-treatment, the corresponding results were considered to determine response.
Percentage of Participants Achieving Histological Response At the end of the 48-week follow-up period at Week 144 Histological response was defined as an improvement by \>/= 2 in the Necroinflammatory Grading and/or by an improvement by \>/= 1 score in Fibrosis Staging according to Ishak. Necroinflammatory Grading ranges 0-14 and is the combined score for necrosis, range 0-10 and inflammation, range 0-4. The participant is scored for only one inflammatory condition. A higher score indicates worse condition. Fibrosis Staging according to Ishak ranges 0-6 and a higher score indicates greater fibrosis.
Percentage of Participants With Lamivudine Genotype Resistance During PEG-IFN+LAM96 Combined Therapy At the end of the treatment period at Week 96 Lamivudine resistance mutations were assessed by detection of the following mutations: rtL80V, rtL80I, rtV173G, rtV173L, rtL180M, rtA181T, rtA181V, rtM204V, rtM204I and rtN236T.
Percentage of Participants Achieving the Combined Response at the End of Treatment At end of treatment at Week 48 or 96 depending on the study arm Combined response was defined as ALT normalization plus lowering of HBV-DNA levels to \<20,000 copies/mL (\<3,400 IU/mL). In case of missing end of treatment measurements, the next available post-treatment value was used.
Change From Baseline of Quantitative Hepatitis B Surface Antigen (HbsAg) Level at the End of Treatment At the end of treatment at Week 48 or 96 depending on the study arm