TDF VS LAM + ADV in LAM + ADV Treated LAM-resistant CHB Patients With Undetectable Hepatitis B Virus DNA

This study is enrolling participants by invitation only.
Sponsor:
Collaborators:
Kyungpook National University
Daegu Catholic University Medical Center
DongGuk University
Pusan National University Hospital
Yeungnam University
Information provided by (Responsible Party):
Jang Byoung Kuk, Keimyung University Dongsan Medical Center
ClinicalTrials.gov Identifier:
NCT01732367
First received: November 19, 2012
Last updated: February 23, 2014
Last verified: February 2014
  Purpose

This study will provide a rationale for switch from lamivudine plus adefovir to tenofovir monotherapy in Lamivudine plus Adefovir Treated Lamivudine-resistant chronic hepatitis B patients with Undetectable Hepatitis B Virus DNA


Condition Intervention Phase
Chronic Hepatitis B
Drug: Lamivudine plus adefovir
Drug: Tenofovir
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Trial of Tenofovir Versus Lamivudine Plus Adefovir in Lamivudine Plus Adefovir Treated Lamivudine-resistant Chronic Hepatitis B Patients With Undetectable Hepatitis B Virus DNA.

Resource links provided by NLM:


Further study details as provided by Keimyung University Dongsan Medical Center:

Primary Outcome Measures:
  • Percentage number of patients with virus reactivation [ Time Frame: Week 96 while on treatment ] [ Designated as safety issue: No ]
    Percentage number of patients with virus reactivation (HBV DNA > 40 IU/mL on two consecutive samples taken 1 month apart, or persistent HBV DNA levels of 20-40 IU/mL on three consecutive 1 month interval) at Week 96 while on treatment.


Secondary Outcome Measures:
  • Virologic response [ Time Frame: Week 96 while on treatment ] [ Designated as safety issue: No ]
    Virologic response Percentage number of patients with virus reactivation at Week 48

  • Antiviral resistance [ Time Frame: Week 96 while on treatment ] [ Designated as safety issue: No ]
    Antiviral resistance percentage number of patients who developed drug resistant mutation at Week 48 and 96 while on randomized therapy.

  • Biochemical response [ Time Frame: Week 96 while on treatment ] [ Designated as safety issue: No ]
    Biochemical response percentage number of patients with biochemical breakthrough at Week 48 and 96

  • Serologic response [ Time Frame: Week 96 while on treatment ] [ Designated as safety issue: No ]
    Serologic response (1) HBeAg loss/seroconversion in HBeAg-positive CHB Percentage number of patients with HBeAg loss or seroconversion at Week 48 and 96.

  • Serologic response [ Time Frame: Week 96 while on treatment ] [ Designated as safety issue: No ]
    Serologic response (2) HBsAg loss Percentage number of patients with HBsAg loss at Week

  • Safety assessment [ Time Frame: Week 96 while on treatment ] [ Designated as safety issue: No ]
    Safety assessment


Estimated Enrollment: 171
Study Start Date: November 2012
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Lamivudine plus adefovir
Continue lamivudine/adefovir add on treatment (standard treatment)
Drug: Lamivudine plus adefovir
Lamivudine 100mg QD for 96 weeks + Adefovir 10mg QD for 96 weeks
Other Names:
  • Zeffix
  • Hepsera
Experimental: Tenofovir
Switch from lamivudine/adefovir add on treatment to tenofovir monotherapy
Drug: Tenofovir
Tenofovir 300mg QD for 96 weeks
Other Name: Viread

Detailed Description:

Recently, in Korea, long-term medication of antiviral agents and their resulting resistance expression have been the most serious cause of failure to treat chronic hepatitis B. Exp.

In particular, the annual resistance rate to lamivudine currently widely being used in Korea amounts to about 15 to 20 percents and the rate is expected to reach 70 to 80 percent in four to five years.

The guidelines by the American Association for the Study of Liver Disease (AASLD) and the European Association for the Study of the Liver (EASL) recommend a combination therapy with adefovir or tenofovir for patients with lamivudine resistant HBV .

In Korea, however, in case of combined prescription of lamivudine and adefovir, only one of them is covered by the health insurance and therefore many patients are difficult to continue treatment due to their economic conditions.

Tenofovir that has been developed most recently and will be placed on sale sooner or later in Korea has strong antiviral effects, causes little or no emergence of resistant viruses, and is known to have lower nephrotoxicity than adefovir.

In particular, several papers reported that tenofovir has effective and sustaining antiviral effects in patients who had other antiviral agents resistant HBV as well as those who received initial treatment. This shows that patients only with lamivudine resistant HBV can be treated only with tenofovir without a combination therapy and when they have low levels of HBV DNA, treatment is relatively effective despite their resistance to adefovir.

Therefore, it is considered that tenofovir switching therapy in patients with undetectable HBV DNA after lamivudine plus adefovir combination therapy to maintain their virus response.

The results of this study will provide a rationale for switch from lamivudine plus adefovir to tenofovir monotherapy in such patients.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female patients aged 18 or older
  • The CHB patients (both HBeAg-positive and - negative) who have at least 6 months undetectable HBV DNA (serum HBV DNA ≤ 20 IU/mL) after lamivudine plus adefovir combination therapy.

Exclusion Criteria:

  • Patients with decompensated liver disease
  • Patients with HCV, HDV or HIV
  • Patients with HCC
  • Serum ALT > 2x ULN level
  • Serum creatinine > 2.0mg/dL
  • Pregnant or lactating women
  • Women who have a plan for pregnancy within the three coming years
  • Patients who have uncontrolled severe concomitant diseases— severe cardiovascular diseases and other infection
  • Those who have no capabilities to understand and sign an informed consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01732367

Locations
Korea, Republic of
Department of Internal Medicine, Keimyung University Dongsan Medical Center
Daegu, Korea, Republic of, ASI|KR|KS002|TAEGU
Sponsors and Collaborators
Keimyung University Dongsan Medical Center
Kyungpook National University
Daegu Catholic University Medical Center
DongGuk University
Pusan National University Hospital
Yeungnam University
Investigators
Principal Investigator: Byoung Kuk Jang, M.D Department of Internal Medicine, Keimyung University Dongsan Medical Center
  More Information

No publications provided

Responsible Party: Jang Byoung Kuk, Keimyung University Dongsan Medical Center
ClinicalTrials.gov Identifier: NCT01732367     History of Changes
Other Study ID Numbers: TDF0001
Study First Received: November 19, 2012
Last Updated: February 23, 2014
Health Authority: Korea: Food and Drug Administration
Korea: Institutional Review Board

Keywords provided by Keimyung University Dongsan Medical Center:
Tenofovir
Lamivudine
Adefovir
Chronic Hepatitis B

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis, Chronic
Digestive System Diseases
DNA Virus Infections
Enterovirus Infections
Hepadnaviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Adefovir
Adefovir dipivoxil
Lamivudine
Tenofovir
Tenofovir disoproxil
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014