Chronic Hepatitis B
Conditions
Keywords
Chronic Hepatitis B, Pegylated Interferon, Lamivudine
Brief summary
The aim is to investigate the best treatment regime of PEG-Intron A and lamivudine combination in terms of viral clearance in chronic hepatitis B patients.
Detailed description
Chronic hepatitis B is a major cause of mortality and morbidity in Hong Kong and most Southeast Asian countries. The efficacy interferon-alfa (IFN-alfa) or lamivudine monotherapy is far from satisfactory with approximately 20% sustained viral response. Extended use of lamivudine is associated with the emergence of drug resistance mutants. As interferon is an immune modulator and lamivudine directly suppresses viral replication, it is therefore logical to combine the 2 drugs for more efficient viral clearance. Previous studies on IFN-alfa and lamivudine combination treatment of chronic hepatitis B showed marginal benefit over lamivudine monotherapy. In these studies, lamivudine was either started 8 weeks prior to IFN-alfa or simultaneous with IFN-alfa. Recently, we have performed a study comparing the efficacy of polyethylene glycol-interferon alfa-2b (PEG-Intron A) and lamivudine versus lamivudine monotherapy for 1 year in the treatment of chronic hepatitis B. In our protocol, PEG-Intron A is started 8 weeks before the commencement of lamivudine, and PEG-Intron A is given for 32 weeks while lamivudine is given for a total of 52 weeks. Our published results suggested PEG-Intron A and lamivudine combination treatment is far superior to lamivudine monotherapy (end of treatment virological response 92% vs 20%, p=0.0015). We are not certain whether the benefit of PEG-Intron A and lamivudine combination in our study is due to our staggered regime, the superiority of PEG-Intron A over IFN-alfa, or both. The aim of this study is to investigate the best treatment regime of PEG-Intron A and lamivudine combination in terms of viral clearance.
Interventions
DRUGPegylated Interferon
DRUGLamivudine
Sponsors
Hoffmann-La Roche
GlaxoSmithKline
Chinese University of Hong Kong
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* HBsAg positive for at least 6 months prior to screening * Serum HBV-DNA \> 10\^6 copies per ml at screening * Serum HBeAg positive at screening * Abnormal ALT (1.3-10x upper limit normal) within one month prior to entry * Compensated liver disease with the following minimum criteria: 1. Hemoglobin within range & not less than 10% from lower normal limit 2. WBC \>= 4,000/mm3 3. Platelets \>= 100,000/mm3 4. Bilirubin normal (except for Gilbert's disease). 5. Albumin stable and normal * Serum creatinine normal or not more than 10% above the upper normal limit * Thyroid Stimulating Hormone (TSH) within normal limits (Patients requiring medication to maintain TSH levels in the normal range are eligible if all other inclusion/
Exclusion criteria
are met.) * Alfa-fetoprotein in normal range (obtained within the previous year, or if elevated and \< 500 ng/ml with a negative ultrasound for hepatocellular carcinoma at screening). * Written informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| HBV DNA reduction at week 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Normalization of ALT & negative HBV DNA at EOT, negative HBV DNA at EOT & 24 weeks after cessation of treatment, normalization of ALT at the end of treatment and 24 weeks after the cessation of treatment, Safety of treatment | — |
Countries
China
Outcome results
None listed