Tenofovir in Asian Chronic Hepatitis B Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01728935
Recruitment Status : Completed
First Posted : November 20, 2012
Last Update Posted : December 30, 2014
Gilead Sciences
Information provided by (Responsible Party):
The University of Hong Kong

Brief Summary:
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.

Condition or disease Intervention/treatment
Chronic Hepatitis B Drug: Tenofovir disoproxil

Detailed Description:

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 141 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Serologic and Virologic Outcomes of Tenofovir in Asian Chronic Hepatitis B Patients With Prior Nucleoside Analogue Exposure
Study Start Date : April 2008
Primary Completion Date : November 2012
Study Completion Date : March 2013

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Tenofovir disoproxil
Tenofovir disoproxil 300mg daily
Drug: Tenofovir disoproxil
Tenofovir disoproxil 300mg daily
Other Name: Viread

Primary Outcome Measures :
  1. Serum HBV DNA levels [ Time Frame: 3 Years ]

Secondary Outcome Measures :
  1. Resistance Profile [ Time Frame: 3 Years ]
    Performed using a Line Probe Assay (LiPA)

  2. HBsAg levels [ Time Frame: 3 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01728935

Hong Kong
Department of Medicine, The University of Hong Kong, Queen Mary Hospital
Hong Kong, Hong Kong
Sponsors and Collaborators
The University of Hong Kong
Gilead Sciences
Principal Investigator: Man-Fung Yuen, MD The University of Hong Kong

Responsible Party: The University of Hong Kong Identifier: NCT01728935     History of Changes
Other Study ID Numbers: TDF-HKU
UW 11-241 ( Other Identifier: Institutional Review Board The University of Hong Kong / Hospital Authority Hong Kong West Cluster )
First Posted: November 20, 2012    Key Record Dates
Last Update Posted: December 30, 2014
Last Verified: December 2014

Keywords provided by The University of Hong Kong:

Additional relevant MeSH terms:
Hepatitis A
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents