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

Hepatitis B, Chronic Clinical Trial

Official title:

An Open-label, Randomized Study to Evaluate the Acute Immunologic Responses in Asian Subjects With E Antigen Positive Chronic Hepatitis B Following Initiation of Therapy for Hepatitis B With Pegasys, Nucleoside Analogues, or Both.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00962871
• Other study ID #: PP22512
• Status: Completed
• Phase: Phase 1
• First received: August 19, 2009
• Last updated: January 14, 2016
• Start date: August 2009
• Est. completion date: February 2012

Study information

• Verified date: January 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: New Zealand: Health Research Council
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: February 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• peginterferon alfa-2a [Pegasys]
360 micrograms sc/week for 2 weeks
• tenofovir
300mg po daily for 2 weeks

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  New Zealand,  Singapore,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Day 1, 3, 5, 8, 10, 14, Week 3, 4, 5, 6 (weeks are computed from the first dose of Pegasys)	No
Secondary	Mean Change From Baseline in HBV-DNA log10	An acute virologic response was determined by change from baseline in HBV-DNA log10.	Day 1, 3, 5, 8, 10, 14, Week 3, 4, 5, 6 (weeks are computed from the first dose of Pegasys)	No
Secondary	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.	Day 1, 5, 14, Week 4 and 6	No

External Links

•   This report describes the early effects of IFNa treatment on immune and viral biomarkers in HBeAg+ CHB patients. The results show that PegIFNa-induced innate immune activation directly benefits from the suppression of HBV replication.