Compare Continuing Lamivudine Plus Adefovir or Adefovir Versus Switching to Entecavir Plus Adefovir in Patients With LAM-resistant Chronic Hepatitis B

Efficacy and Safety of Continuing Lamivudine Plus Adefovir or Adefovir Versus Switching to Entecavir Plus Adefovir in Patients With Chronic Hepatitis B Who Have Resistant Mutants to Lamivudine and Show Suboptimal Response to Combination of Lamivudine Plus Adefovir or Adefovir Monotherapy

The purpose of this study is to compare efficacy and safety of continuing Lamivudine plus Adefovir or Adefovir versus switching to Entecavir plus Adefovir in patients with LAM-resistant chronic hepatitis B who have suboptimal response to Lamivudine plus Adefovir or Adefovir

Study Overview

• Status: Unknown
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Drug: Lamivudine; Drug: Adefovir; Drug: Entecavir

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Danbi Lee; Phone Number: 82)2-3010-3907; Email: leighdb@hanmail.net

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Recruiting
    • Asan Medical Center
    • Contact: Young Hwa Chung

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Chronic hepatitis B
• Age ≥ 20 year old
• Currently taking Lamivudine and Adefovir combination therapy or Adefovir monotherapy for chronic HBV infection for 24 weeks
• Proven Lamivudine resistant mutation
• HBV DNA levels at screening ≥ 15 IU/mL
• Females must be post-menopausal, unable to conceive, or test negative for pregnancy via urine test
• Patient is able to give written informed consent prior to study start and to comply with the study requirements

Exclusion Criteria:

• A history or current of decompensated cirrhosis or hepatocellular carcinoma
• Currently receiving antiviral, immunomodulatory, cytotoxic or corticosteroid therapy
• Co-infected with HCV or HIV
• A history of organ transplantation
• Pregnant or breast-feeding
• Current clinically relevant of abuse of alcohol or drugs.
• Significant immunocompromised, gastrointestinal, renal(serum creatinine ≥ 1.5 mg/dL), hematological, psychiatric, bronchopulmonary, biliary diseases excluding asymptomatic GB stone, neurological, cardiac, oncologic, allergic disease or medical illness that in the investigator's opinion might interfere with therapy
• malignancy in previous 5 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Lamivudine plus Adefovir or Adefovir; Lamivudine+Adefovir or Adefovir for 48 weeks	Drug: Lamivudine; Lamivudine 100mg/day orally; Drug: Adefovir; Adefovir 10mg/day orally
Experimental: Entecavir plus Adefovir; Entecavir+Adefovir for 48 weeks	Drug: Adefovir; Adefovir 10mg/day orally; Drug: Entecavir; Entecavir 1mg/day orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients with HBV DNA<15IU/mL	week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with HBV DNA<15IU/mL		Day1, week12, week 24, week 36, week 48
The change of HBV DNA from the baseline		week 48
Proportion of patients with ALT normalization		Day1, week12, week 24, week 36, week 48
Proportion of patients with HBeAg loss and/or seroconversion		Day1, week12, week 24, week 36, week 48
The change of HBsAg from the baseline		week 48
Proportion of patients with HBsAg loss and/or seroconversion		week 24, week 48
Proportion of patients who experienced virologic breakthrough		week 48
Assessment the safety in all patients (composite measure of AE, labs, phys. exam, vital signs)	Composite outcome measure consisting of multiple measures, including: Number of patients with Adverse events( including SAEs); Frequency and severity of Abnormalities in laboratory examinations; BUN, Albumin, AST, ALT,GGT, Creatinine, Hemoglobin, Hematocrit, Platelet Count, Prothrombin time; Number of patients with Abnormalities in physical examinations; Eyes/Ears/Nose/Throat, Respiratory, Cardiovascular, Dermatological, Abdominal, Musculoskeletal, Other; Number of patients with Abnormalities in vital signs ; pulse rate( beats per minute), Blood pressure(mmHg), Height(cm), weight(kg)	week 48

Collaborators and Investigators

• Sponsor: Asan Medical Center

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Anticipated): January 1, 2017
• Study Completion (Anticipated): May 1, 2017

Study Registration Dates

• First Submitted: June 1, 2015
• First Submitted That Met QC Criteria: June 25, 2015
• First Posted (Estimate): June 26, 2015

Study Record Updates

• Last Update Posted (Estimate): December 30, 2015
• Last Update Submitted That Met QC Criteria: December 29, 2015
• Last Verified: December 1, 2015

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, Chronic; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Entecavir; Lamivudine; Adefovir
• Other Study ID Numbers: ENTADE