Tenofovir Disoproxil Fumarate vs. Entecavir in Chronic Hepatitis B Patients With Partial Virologic Response to Entecavir

NCT01711567 | Completed Phase 4 DMC

• 1 other identifier: STEEP study
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Entecavir, a potent antiviral agent, has been widely used for treatment-naïve chronic hepatitis B patients. However, about 20% of patients showed partial virologic response after 2 year of entecavir therapy (33% in HBeAg positive, 10% in HBeAg negative patients). Tenofovir is a nucleotide analogue with more potent antiviral activity. In addition, there is no cross resistance between the two drugs. Therefore it is assumed that tenofovir would be effective in the treatment of chronic hepatitis B patients who shows partial virologic response (detectable HBV DNA by real time PCR after 12 months of treatment) despite treatment with entecavir. In this study, we will compare the efficacy of switching to tenofovir with continuing entecavir in patients who shows partial virologic response to entecavir.

Conditions

Chronic Hepatitis B

Keywords

Chronic Hepatitis B; TENOFOVIR; ENTECAVIR; PARTIAL RESPONDER

Outcome Measures

Primary Outcomes (1)

• Virologic response rate at year 1 (12 months) (HBV DNA < 20 IU/mL)

  up to the end of year 1 (12 months)

Secondary Outcomes (1)

• -Degree of HBV DNA reduction, mean HBV DNA, biochemical and serologic response rates, resistance, and adverse events at year 1

  up to the end of year 1 (12 months)

Study Arms (2)

entecavir

ACTIVE COMPARATOR

standard drugs

Drug: entecavir

tenofovir

ACTIVE COMPARATOR

study drugs

Drug: tenofovir

Interventions

tenofovir DRUG

tenofovir 300 mg qd

Also known as: tenofovir (viread)

tenofovir

entecavir DRUG

entecavir 0.5 mg qd

Also known as: entecavir(baraclude) 0.5 mg qd

entecavir

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• CHB patients (positive HBsAg more than 6 months)
• Age 19 years old
• HBeAg positive or negative patients
• Patients receiving entecavir 0.5 mg more than 12 months
• Detectable HBV DNA by real time PCR (HBV \> 60 IU/mL)
• Compensated liver function (Child-Pugh-Turcotte score ≤7, prothrombin time 3 sec above ULN or INR ≤1.5, serum albumin \>3 g/dL, total bilirubin \<2.5 mg/dL, no history of variceal bleeding, diuretics or ascites requiring paracentesis, hepatic encephalopathy)

You may not qualify if:

• History of treatment with nucleotide analogue other than 0.5 mg of ETV
• Serum creatinine level \> 1.5 mg/dL or creatinine clearance \< 50 mL/min
• Absolute neutrophil count ≤ 1000 cell/mL
• Hemoglobin level ≤ 10 g/dL in men or ≤ 9 g/dL in women
• Antiviral resistance mutations on rtT184, rtS202, or rtM250 + rtM204V/I
• A positive antibody test for human immunodeficiency virus, hepatitis C virus, or hepatitis D virus
• Pregnancy or lactation
• HCC (in cases where alfa-fetoprotein levels were over 100 ng/mL, abdominal computed tomography or magnetic resonance image was performed to exclude HCC)
• Untreated malignancy other than HCC.

Sponsors & Collaborators

• Korea University: lead
• Gilead Sciences: collaborator

Study Sites (1)

Korea University Ansan Hospital

Ansan, Gyeonggi-do, 425-707, South Korea

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

Tenofovir; entecavir

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Hyung Joon Yim, M.D.

  Korea University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: October 17, 2012
• First Posted: October 22, 2012
• Study Start: April 1, 2013
• Primary Completion: December 1, 2015
• Study Completion: November 1, 2016
• Last Updated: November 9, 2016

Record last verified: 2016-11

Locations

KR (1)