Tenofovir in Asian Chronic Hepatitis B Patients

NCT ID: NCT01728935

Last Updated: 2014-12-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

141 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-04-30

Study Completion Date

2013-03-31

Brief Summary

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Tenofovir (TDF) has been demonstrated to have potency antiviral against the hepatitis B virus (HBV) in various multiple-centre trials, with no cases of resistance encountered. However, its efficacy and resistance profile in the Asian population, which constitute the majority of chronic hepatitis B (CHB) patients, is unknown. Compared to other nucleoside analogues, TDF has been associated with relatively high rates of hepatitis B surface antigen (HBsAg) seroclearance. It would be interested to see if this could be reproduced. The investigators plan to report the serologic and virologic results of our 140 nucleoside analogue-experienced patients who were commenced on TDF.

Detailed Description

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Recent multi-center trials have shown tenofovir disoprovil fumarate (TDF) demonstrating potent antiviral efficacy in both nucleoside-naive and -experienced chronic hepatitis B (CHB) patients. At present, there has been no identifiable amino acid substitutions associated with resistance to TDF.

Since TDF and adefovir (ADV), another licensed drug for CHB, belong to same molecular group, acyclic phosphonate, there had been various studies investigating the efficacy of TDF in ADV-resistant patients. The efficacy of tenofovir in this group of patients is conflicting. While several studies have shown TDF achieving similar viral suppression when compared to CHB patients without ADV-resistance , another study found that patients with the signature ADV mutations of rtA181V/T and /or rtN236T responded suboptimally to TDF. For all published studies, the number of patients with documented genotypic resistance to adefovir is actually small (n = 17-40), and therefore, further studies in this area are required.

Another interesting point to note was the relatively high rate of hepatitis B surface antigen (HBsAg) seroclearance found in patients taking TDF. The cumulative rate of HBsAg seroclearance up in hepatitis B e antigen (HBeAg)-positive was 10% after 4 years . However, the same study did not find any HBeAg-negative patients achieving HBsAg seroclearance. In addition, studies on TDF were mainly performed in Caucasian patients, the majority being genotypes A and D. A preliminary study performed in Asian patients, predominantly genotypes B and C, did not discover any cases of HBsAg seroclearance . Given the majority of the CHB population is found in Asia, further studies are needed to clarify if HBsAg seroclearance by nucleoside / nucleotide analogues is potentially achievable using TDF.

Conditions

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Chronic Hepatitis B

Keywords

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HBV Tenofovir HBV DNA HBsAg Resistance

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Tenofovir disoproxil

Tenofovir disoproxil 300mg daily

Group Type OTHER

Tenofovir disoproxil

Intervention Type DRUG

Tenofovir disoproxil 300mg daily

Interventions

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Tenofovir disoproxil

Tenofovir disoproxil 300mg daily

Intervention Type DRUG

Other Intervention Names

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Viread

Eligibility Criteria

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Inclusion Criteria

1. HBsAg-positivity for at least 6 months at presentation
2. Commenced on tenofovir for chronic hepatitis B
3. Exposure to other nucleoside analogues before starting TDF

Exclusion Criteria

1. Concomitant liver diseases including chronic hepatitis C and/ or D infection, Wilson's disease, autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis.
2. Significant alcohol intake (\> 20 grams per day)
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role collaborator

The University of Hong Kong

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Man-Fung Yuen, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Hong Kong

Locations

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Department of Medicine, The University of Hong Kong, Queen Mary Hospital

Hong Kong, , Hong Kong

Site Status

Countries

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Hong Kong

Other Identifiers

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UW 11-241

Identifier Type: OTHER

Identifier Source: secondary_id

TDF-HKU

Identifier Type: -

Identifier Source: org_study_id