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

Primary Purpose

Chronic Hepatitis B

Status

Completed

Phase

Phase 4

Locations

Korea, Republic of

Study Type

Interventional

Intervention

tenofovir

entecavir

About this trial

This is an interventional treatment trial for Chronic Hepatitis B focused on measuring Chronic Hepatitis B, TENOFOVIR, ENTECAVIR, PARTIAL RESPONDER

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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)

Exclusion Criteria:

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.

Sites / Locations

Korea University Ansan Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

entecavir

tenofovir

Arm Description

standard drugs

study drugs

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

NCT ID

NCT01711567

First Posted

October 17, 2012

Last Updated

November 8, 2016

Sponsor

Korea University

Collaborators

Gilead Sciences

1. Study Identification

Unique Protocol Identification Number

NCT01711567

Brief Title

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

Acronym

STEEP

Official Title

Switching to Tenofovir Disoproxil Fumarate vs. Continuing Entecavir in Chronic Hepatitis B Patients With Partial Virologic Response During Entecavir Therapy: STEEP Study

Study Type

Interventional

2. Study Status

Record Verification Date

November 2016

Overall Recruitment Status

Completed

Study Start Date

April 2013 (undefined)

Primary Completion Date

December 2015 (Actual)

Study Completion Date

November 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Korea University

Collaborators

Gilead Sciences

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

The number of patients needed was calculated using PASS 2008. We hypothesized that two-thirds (65%) of the patients receiving TDF, and one-fifth (20%) of the patients receiving ETV, would achieve virologic response. We also assumed a 15% drop-out rate; thus, 22 patients were needed in each group to achieve 80% power to demonstrate a difference between the groups with a 5% level of significance. The primary efficacy end point will be analyzed on a per-protocol basis, including only those patients who had completed the treatment schedule of study. In contrast, the intention-to-treat analysis will include all randomized subjects, even those dropped-out from the study before 12 months, as cases of treatment failure.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Hepatitis B

Keywords

Chronic Hepatitis B, TENOFOVIR, ENTECAVIR, PARTIAL RESPONDER

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

60 (Actual)

8. Arms, Groups, and Interventions

Arm Title

entecavir

Arm Type

Active Comparator

Arm Description

standard drugs

Arm Title

tenofovir

Arm Type

Active Comparator

Arm Description

study drugs

Intervention Type

Drug

Intervention Name(s)

tenofovir

Other Intervention Name(s)

tenofovir (viread)

Intervention Description

tenofovir 300 mg qd

Intervention Type

Drug

Intervention Name(s)

entecavir

Other Intervention Name(s)

entecavir(baraclude) 0.5 mg qd

Intervention Description

entecavir 0.5 mg qd

Primary Outcome Measure Information:

Title

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

Time Frame

up to the end of year 1 (12 months)

Secondary Outcome Measure Information:

Title

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

Time Frame

up to the end of year 1 (12 months)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

19 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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) Exclusion Criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Hyung Joon Yim, M.D.

Organizational Affiliation

Korea University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Korea University Ansan Hospital

City

Ansan

State/Province

Gyeonggi-do

ZIP/Postal Code

425-707

Country

Korea, Republic of

12. IPD Sharing Statement

Learn more about this trial

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

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