Adefovir and Lamivudine for Entecavir Resistance (ALTER Study) (ALTER)

February 14, 2014 updated by: Hyung Joon Yim, Korea University

Efficacy of Adefovir and Lamivudine Combination Therapy in Patients With Entecavir Resistance

  • Entecavir has been one of the option for treatment of lamivudine resistant chronic hepatitis B (CHB).
  • In case of entecavir resistance, adefovir could be used. However, sequential monotherapy may result in multidrug resistance.
  • It is thought that adefovir and lamivudine combination therapy reduce the risk of adefovir resistance, thereby continued therapy will lead to suppression of hepatitis B virus (HBV) DNA to be undetectable in patients with entecavir resistance.
  • This study aim to evaluate the efficacy of adefovir and lamivudine combination therapy in CHB patients with entecavir resistance.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Entecavir is a potent antiviral agent for the treatment of chronic hepatitis B (CHB). However, the incidence of entecavir resistance increases over 50% at 5th year in lamivudine-refractory CHB patients. Considering cross resistance profile, adefovir is a good option for managing entecavir resistance. However adefovir monotherapy may lead to adefovir resistance, because entecavir resistant hepatitis B virus (HBV) retain lamivudine resistance. Previously, combination of adefovir and lamivudine was reported to be effective in a patient with entecavir resistance, but only as a case report form. No further data are available on this combination therapy in a sufficient number of patients. It is thought that adefovir and lamivudine combination therapy reduce the risk of adefovir resistance, thereby continued combination treatment will result in suppression of HBV DNA to be undetectable in patients with entecavir resistance.

The aim of this study is to evaluate the efficacy of adefovir and lamivudine combination therapy in CHB patients with entecavir resistance.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
      • Incheon, Korea, Republic of
        • Inha University Hospital
      • Incheon, Korea, Republic of
        • Gachon University Gil Medical Center
      • Seoul, Korea, Republic of
        • Korea University Anam Hospital
      • Seoul, Korea, Republic of
        • Hallym University, Gangnam Sacred Heart Hospital
    • Chngcheongbuk-do
      • Cheongju, Chngcheongbuk-do, Korea, Republic of
        • Chungbuk National University Hospital
    • Gangwon-do
      • Wonju, Gangwon-do, Korea, Republic of
        • Yonsei University Wonju Christian Hospital
    • Gyeonggi
      • Ansan, Gyeonggi, Korea, Republic of
        • Korea University Ansan Hospital
    • Gyeonggi-do
      • Anyang, Gyeonggi-do, Korea, Republic of
        • Hallym University, Sacred Heart Hospital
      • Euijeongbu, Gyeonggi-do, Korea, Republic of
        • The Catholic University of Korea, Euijeongbu Saint Mary's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Chronic hepatitis B patients (positive HBsAg > 6 months)
  2. Age > 18 year old
  3. History of treatment with entecavir more than 6 months
  4. Proven entecavir resistant mutation (rtT184S/A/I/L/G/C/M, rtS202G/C/I, or rtM250I/V)
  5. HBV DNA level> 2000 IU/mL
  6. Compensated liver disease (Child-Pugh-Turcotte score over 7; prothrombin time prolonged more than 3 sec above ULN or INR over 1.5; serum albumin >3 g/dL; total bilirubin <2.5 mg/dL; No history of variceal bleeding, ascites, or hepatic encephalopathy)
  7. Patients willing to give informed consent

Exclusion Criteria:

  1. Out of inclusion criteria

  2. Any one of following

    • Serum phosphorus level under 2.4 mg/dL
    • Serum creatinine level over 1.5 mg/dL or creatinine clearance <50 mL/min
    • Absolute neutrophil count lower than 1000 cell/mL
    • Hb level under 10 g/dL (male), under 9 g/dL (female)
    • Serum AFP >100 ng/mL
  3. History of treatment with interferon-alfa, thymosin-alfa 1, or nucleos(t)ide analogue other than entecavir in 6 months of screening
  4. History of adefovir resistance (detection of rtA181T/Vor rtN236T at screening or in the past)
  5. Recipient of organ transplantation
  6. Positive antibody test to HIV, HCV or HDV
  7. Pregnant or breast feeding women
  8. Patients with hepatocellular carcinoma or uncontrolled malignant disease
  9. Habitual alcohol drinker (>140 g/week for men, >70 g/week for women) -

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Adefovir and lamivudine combination
Drug: ADEFOVIR, LAMIVUDINE
Adefovir/10mg tablet/once a day/52week Lamivudine/100mg tablet/once a day/52week
Other Names:
  • Lamivudine (Zeffix)
  • Adefovir (Hepasera)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Degree of HBV DNA reduction from baseline
Time Frame: at week 52
Degree of HBV DNA reduction from baseline during 52 week-period of adefovir and lamivudine combination therapy will be assessed.
at week 52

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
HBV DNA undetectability by PCR (<60 IU/mL)
Time Frame: at week 52
at week 52
ALT normalization
Time Frame: at week 52
at week 52
HBeAg loss
Time Frame: at week 52
at week 52
HBeAg to anti- HBe seroconversion
Time Frame: at week 52
at week 52
Development of adefovir resistance
Time Frame: at week 52
at week 52
Virologic breakthrough
Time Frame: at week 52
virologic breakthrough is defined by increase of HBV DNA above 10 times the lowest level (na dir).
at week 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Korea University

Collaborators

GlaxoSmithKline

Investigators

  • Principal Investigator: HYUNG JOON YIM, M.D., Ph.D., Korea University Ansan Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2010

Primary Completion (Actual)

February 1, 2012

Study Completion (Actual)

February 1, 2014

Study Registration Dates

First Submitted

December 22, 2011

First Submitted That Met QC Criteria

March 1, 2012

First Posted (Estimate)

March 7, 2012

Study Record Updates

Last Update Posted (Estimate)

February 17, 2014

Last Update Submitted That Met QC Criteria

February 14, 2014

Last Verified

February 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ALTER_114093

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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