Tenofovir in Asian Chronic Hepatitis B Patients

Chronic Hepatitis B Clinical Trial

Official title:

Serologic and Virologic Outcomes of Tenofovir in Asian Chronic Hepatitis B Patients With Prior Nucleoside Analogue Exposure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01728935
• Other study ID #: TDF-HKU
• Secondary ID: UW 11-241
• Status: Completed
• Phase: N/A
• First received: November 8, 2012
• Last updated: December 29, 2014
• Start date: April 2008
• Est. completion date: March 2013

Study information

• Verified date: December 2014
• Source: The University of Hong Kong
• Contact: n/a
• Is FDA regulated: No
• Health authority: Hong Kong: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 141
• Est. completion date: March 2013
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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)

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• Tenofovir disoproxil
Tenofovir disoproxil 300mg daily

Locations

Country	Name	City	State
Hong Kong	Department of Medicine, The University of Hong Kong, Queen Mary Hospital	Hong Kong

Sponsors (2)

Lead Sponsor	Collaborator
The University of Hong Kong	Gilead Sciences

Country where clinical trial is conducted

Hong Kong, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum HBV DNA levels		3 Years	No
Secondary	Resistance Profile	Performed using a Line Probe Assay (LiPA)	3 Years	No
Secondary	HBsAg levels		3 years	No