Maintaining Antiviral Efficacy After Switching to Generic Entecavir 1 mg for Chronic Hepatitis B

Maintaining Antiviral Efficacy After Switching to Generic Entecavir, Baracle® in Patients Taking Baraclude® 1 mg for Antiviral Resistant Chronic Hepatitis B; A Noninferiority Study Assessing Non-detection Rate of Hepatitis B Virus DNA

Entecavir 1 mg is commonly used in patients with chronic hepatitis B (CHB) patients with previous antiviral resistance. This study evaluates the efficacy and safety of switching to generic entecavir 1 mg (Baracle®, Dong-A Science Technology) in CHB patients taking brand name entecavir 1 mg (Baraclude®, Bristol-Myers Squibb) alone or in combination with other nucleos(t)ide analogues after the development of antiviral resistance.

The primary aim is virological response (<20 IU/mL) at 12 months

Study Overview

• Status: Unknown
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: Switching to Generic Entecavir (Baracle®)

Detailed Description

This study is a prospective single-arm open-label trial. The primary endpoint is virological response (<20 IU/mL) at 12 months after switching treatment.

Patients who satisfy the inclusion and exclusion criteria will switch from Baraclude® 1 mg to Baracle®. Assessment of treatment response at 12 months is performed by comparing undetectable HBV DNA rates between baseline and 12 months after switching therapy.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gyeonggi-do
    • Ansan, Gyeonggi-do, Korea, Republic of, 15355
      • Korea University Ansan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age >19 years old CHB patients
• Confirmed antiviral resistance
• Taking brand entecavir 1 mg for more than 1 year
• HBV DNA < 20 IU/mL
• Compensated liver cirrhosis
• Willing to participate

Exclusion Criteria:

• Failure to meet the inclusion criteria
• Cr>1.5 mg/dL
• Postive HCV Ab
• Decompensated cirrhosis
• Pregnant women
• HCC
• Alcoholics

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Baracle; Chronic hepatitis B patients who swiched to Baracle® 1 mg from Baraclude® 1 mg treatment as mono- or combination therapy after the development of antiviral resistance to nucleos(t)ide analogues	Drug: Switching to Generic Entecavir (Baracle®); switching to Baracle® 1 mg (generic drug) in chronic hepatitis B patients taking Baraclude® 1 mg (brand drug); Other Names: Antiviral therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-detection rate of hepatitis B virus DNA	undetectable HBV DNA (<20 IU/mL) at 12 months after switching treatment.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Normalization of liver enzyme	ALT < 40 IU/L	12 months
Loss of serological markers of hepatitis B e antigen	Loss of HBeAg	12 months
Signs of newly developing antiviral resistance	Elevation of hepatitis B virus DNA by 10 fold assessed by real time PCR	12 months

Collaborators and Investigators

• Sponsor: Korea University
• Investigators: Principal Investigator: Hyung Joon Yim, MD, Korea University

Publications and helpful links

General Publications

• European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017 Aug;67(2):370-398. doi: 10.1016/j.jhep.2017.03.021. Epub 2017 Apr 18.
• Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, Brown RS Jr, Bzowej NH, Wong JB. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018 Apr;67(4):1560-1599. doi: 10.1002/hep.29800. No abstract available.
• Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines for management of chronic hepatitis B. Clin Mol Hepatol. 2019 Jun;25(2):93-159. doi: 10.3350/cmh.2019.1002. Epub 2019 Jun 12. No abstract available.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2016
• Primary Completion (ACTUAL): March 1, 2019
• Study Completion (ANTICIPATED): December 31, 2020

Study Registration Dates

• First Submitted: August 23, 2019
• First Submitted That Met QC Criteria: August 24, 2019
• First Posted (ACTUAL): August 28, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 17, 2020
• Last Update Submitted That Met QC Criteria: February 12, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic; Anti-Infective Agents; Antiviral Agents; Entecavir
• Other Study ID Numbers: 2106AS0033

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No