Pilot Study of First Line Combination Treatment With Low Dose Pegylated Interferon and Entecavir in Treatment-naïve Patients With Chronic Hepatitis B.
Trial Snapshot
- Phase
- Phase 1
- Sponsor
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Combination of half dose and reduced duration pegalyted interferon in combination with entecavir achieves biochemical and virologic response in chronic hepatitis B
Study Overview
Brief Summary
According to published literature, treatment with pegylated interferon (Peg-IFN) is associated with end of treatment response in treatment naive patients with chronic hepatitis B (CHB). It has antiviral as well as anti-fibrotic properties and treatment with Peg-IFN results in improvement of liver histology and down regulation of progression to cirrhosis of liver. Peg-IFN is administered for a finite duration. The major limitation of Peg-IFN is that only 30-49% patients are benefited by this anti-viral drug. Another potent anti-viral drug, entecavir (ETV), on the other hand, reduces HBV replication in most patients, but causes improvement of liver histology in only 30%, possibly because of its lack of immune modulatory ability like Peg-IFN. Also, ETV treatment is associated with several complications like emergence of HBV mutant. The aim of this study is to assess whether the combination of these two 'unique' anti-viral drugs offer the best possible outcome to treatment-naïve CHB patients, in terms of treatment response (virological and biochemical), treatment cost and duration and adverse events.
Detailed Description
Aims & Objectives:
Peg-IFN has five unique features, namely (i) finite duration of administration, (ii) anti-viral effect, (iii) immune-modulation, (iv) anti-fibrotic effect and (v) delayed virologic response off-treatment. However these benefits come at a cost i.e. the drug is expensive and there are several known adverse events.
ETV is a potent nucleoside analogue (Nuc), which has minimal resistance compared to most other Nucs. It is efficient for inducing rapid decline of HBV DNA. However ETV has no known immune modulatory or anti-fibrotic effect and therefore off-treatment response or improvement of hepatic histology is not expected with ETV. Similar to other NUCs, there is no defined duration of administration of ETV.
It has been hypothesized that if lower-dose of Peg-IFN can be given in combination with ETV in treatment-naïve CHB patients, they are likely to benefit most from the 'best of both the drugs' in terms of viral and biochemical responses, treatment cost and duration and adverse events.
The project aims to evaluate the outcome of first-line combination treatment with 'lower-dose Peg-IFN plus ETV' in treatment-naïve CHB patients to see whether this combination may be further evaluated and eventually recommended as first-line management for HBV related chronic liver diseases (CLD).
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 20 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •HBsAg positive >6 months, HBeAg positive or negative, serum ALT normal or raised and HBV DNA >1000 copies/ml in HBeAg negative or HBV DNA >10000 copies/ml in HBeAg positive.
Exclusion Criteria
- •Coinfection with HCV or HIV, cirrhosis of liver
Arms & Interventions
Pegylated Interferon, Entecavir
'Pegylated Interferon, Entecavir' arm will consist of 20 chronic hepatitis B patients who will receive Pegylated Interferon 90 micro gms subcutaneously once weekly in combination with entecavir 0.5 mg orally once daily for 24 weeks
Intervention: Pegalyted interferon, Entecavir (Drug)
Outcomes
Primary Outcomes
Combination of half dose and reduced duration pegalyted interferon in combination with entecavir achieves biochemical and virologic response in chronic hepatitis B
Time Frame: 6 months
Combination of half dose and reduced duration pegalyted interferon in combination with entecavir achieves biochemical and virologic response in chronic hepatitis B
Secondary Outcomes
No secondary outcomes reported
Investigators
Dr. Mamun-Al-Mahtab
Associate Professor of Hepatology
Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh