A Study of Early Immunologic Response in Asian Patients With Chronic Hepatitis B, Treated With Pegasys (Peginterferon Alfa-2a (40KD)), Nucleoside Analogues, or Both

Hoffmann-La Roche30 enrolled

Overview

This open-label, randomized, parallel-arm study will assess the early immunologic response in treatment-naïve Asian male patients with chronic hepatitis B after initiation of treatment with Pegasys or tenofovir or Pegasys plus tenofovir. Patients will be randomized to one of 4 cohorts to receive either Pegasys (360mcg subcutaneously weekly) or tenofovir (300mg orally daily) or both or no treatment for 2 weeks. After 2 weeks on study treatment, patients may opt to receive standard of care treatment with Pegasys. Target sample size is \<50.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hepatitis B, Chronic

Interventions

peginterferon alfa-2a [Pegasys]

Eligibility

Sex: MALEMin age: 18 YearsMax age: 55 Years

Medical Language ↔ Plain English

Inclusion Criteria: * male adults of Southeast and/or East Asian origin, 18-55 years of age * HBeAg-positive chronic hepatitis B * detectable HBV DNA Exclusion Criteria: * prior antiviral therapy for chronic hepatitis B * evidence of bridging fibrosis, cirrhosis or decompensated liver disease * positive test at screening for HAV (IgM), HCV, HDV or HIV * history or evidence of medical condition associated with chronic liver disease * antineoplastic or immunomodulatory treatment \</=6 months prior to first dose of study drug

Locations (6)

Unnamed facility

Los Angeles, California, United States

Unnamed facility

San Francisco, California, United States

Unnamed facility

Grafton, New Zealand

Unnamed facility

Singapore, Singapore

Unnamed facility

Singapore, Singapore

Unnamed facility

Taipei, Taiwan

Outcomes

Primary Outcomes

Mean Change From Baseline in Viral Quantitative e Antibody

An acute virologic response was determined by change from baseline in viral antigen/antibody laboratory data.

Time frame: Day 1, 3, 5, 8, 10, 14, Week 3, 4, 5, 6 (weeks are computed from the first dose of Pegasys)

Secondary Outcomes

Mean Change From Baseline in HBV-DNA log10

An acute virologic response was determined by change from baseline in HBV-DNA log10.

Time frame: Day 1, 3, 5, 8, 10, 14, Week 3, 4, 5, 6 (weeks are computed from the first dose of Pegasys)

Early Changes in Viral Sequence Associated With Viral Suppression

Viral sequence data was obtained from the first 10 participants enrolled in Study but on analysis of the data, numerous low frequency deviations from the HBV consensus sequences were observed in the 454 SLX sequence data which were not replicated in data obtained from routine Sanger sequencing. These sequence deviations did not correspond to a temporal pattern consistent with selection of mutations following HBV treatment. Moreover, they could not be reliably distinguished from sequencing artifacts. It was also revealed that complete genome coverage was not obtained due to errors in the design of the primer sequences. For these reasons, further sequence analyses were not performed for the remaining treatment population.

Time frame: Day 1, 5, 14, Week 4 and 6