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

Chronic Hepatitis B Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01711567
• Other study ID #: STEEP study
• Status: Completed
• Phase: Phase 4
• First received: October 17, 2012
• Last updated: November 8, 2016
• Start date: April 2013
• Est. completion date: November 2016

Study information

• Verified date: November 2016
• Source: Korea University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: November 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

1. CHB patients (positive HBsAg more than 6 months)

2. Age 19 years old

3. HBeAg positive or negative patients

4. Patients receiving entecavir 0.5 mg more than 12 months

5. Detectable HBV DNA by real time PCR (HBV > 60 IU/mL)

6. 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:

1. History of treatment with nucleotide analogue other than 0.5 mg of ETV

2. Serum creatinine level > 1.5 mg/dL or creatinine clearance < 50 mL/min

3. Absolute neutrophil count = 1000 cell/mL

4. Hemoglobin level = 10 g/dL in men or = 9 g/dL in women

5. Antiviral resistance mutations on rtT184, rtS202, or rtM250 + rtM204V/I

6. A positive antibody test for human immunodeficiency virus, hepatitis C virus, or hepatitis D virus

7. Pregnancy or lactation

8. HCC (in cases where alfa-fetoprotein levels were over 100 ng/mL, abdominal computed tomography or magnetic resonance image was performed to exclude HCC)

9. Untreated malignancy other than HCC.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel 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
tenofovir 300 mg qd
• entecavir
entecavir 0.5 mg qd

Locations

Country	Name	City	State
Korea, Republic of	Korea University Ansan Hospital	Ansan	Gyeonggi-do

Sponsors (2)

Lead Sponsor	Collaborator
Korea University	Gilead Sciences

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Virologic response rate at year 1 (12 months) (HBV DNA < 20 IU/mL)		up to the end of year 1 (12 months)	Yes
Secondary	-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)	Yes