A Study to Compare and Evaluate Intrahepatic cccDNA Reduction After Administrating Clevudine or Entecavir in the Chronic HBV Patients

This is a open, randomized, parallel study. Subjects will have Clevudine or Entecavir therapy for 48 weeks(Clevudine:Entecavir = 2:1), and subjects who have Complete Response(HBV DNA negative and ALT normal) will have follow-up period for additional 48 weeks.

Study Overview

• Status: Terminated
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: Clevudine; Drug: Entecavir

• Study Type: Interventional
• Enrollment (Anticipated): 75
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • 9 Sites

Participation Criteria

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. Patient who is older than 18.
2. Patient who is HBsAg positive for the previous 6 months and with HBV DNA ≥ 1 x 10^5 copies/mL
3. Patient who is HBeAg negative.
4. Patient with ALT≥1×ULN.
5. Patient who is able to give written informed consent prior to study start and to comply with the study requirements.

Exclusion Criteria:

1. Patient is currently receiving antiviral, immunomodulatory, cytotoxic or corticosteroid therapy.
2. Patient is treated with interferon for the previous 6 months.
3. Patient has been treated previously with clevudine, lamivudine, adefovir, entecavir, telbivudine or any other investigational nucleoside for HBV infection.
4. Patient is coinfected with HCV, HDV or HIV.
5. Patient has evidence of ascites, variceal hemorrhage and/or hepatic encephalopathy.
6. Patient has evidence of decompensated Liver cirrhosis and/or hepatocellular carcinoma.
7. Patient has a history of organ transplantation.
8. Patient has the treatment of nephrotoxicity drugs, competitive drugs for kidney to excrete, and/or hepatotoxicity drugs for the previous 2 months from screening.
9. Patient is pregnant or breast-feeding.
10. Patient has a clinically relevant history of abuse of alcohol or drugs.
11. Patient has a significant immunocompromised, gastrointestinal, renal, 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. The patient with a benign tumor, excluded if judged by an investigator that the continuation of study would be interfered by the tumor.
12. Patient has creatinine clearance less than 60mL/min as estimated by the following formula: (140-age in years) (body weight [kg])/(72) (serum creatinine [mg/dL]) [Note: multiply estimates by 0.85 for women]

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
Experimental: 1; Clevudine 30mg	Drug: Clevudine; 30mg,QD; Other Names: Levovir
Active Comparator: 2; Entecavir 0.5mg	Drug: Entecavir; 0.5mg QD; Other Names: Baraclude

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Intrahepatic cccDNA reduction from baseline	week 48

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients with HBV DNA below LOD by real-time PCR	day1(predose), every 12 weeks during treatment period(48weeks), every 8 weeks during follow-up period(48weeks)
Reduction of HBV DNA level from baseline	day1(predose), every 12 weeks during treatment period(48weeks), every 8 weeks during follow-up period(48weeks)
ALT normalization	day1(predose), every 12 weeks during treatment period(48weeks), every 8 weeks during follow-up period(48weeks)
Reduction of sAg titer from baseline	day1(predose), every 12 weeks during treatment period(48weeks), every 8 weeks during follow-up period(48weeks)
Proportion of maintaining sustained effect	every 8 weeks during follow-up period(48weeks)

Collaborators and Investigators

• Sponsor: Bukwang Pharmaceutical

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: December 19, 2010
• First Submitted That Met QC Criteria: December 22, 2010
• First Posted (Estimate): December 24, 2010

Study Record Updates

• Last Update Posted (Estimate): December 18, 2014
• Last Update Submitted That Met QC Criteria: December 16, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: HBe Ag(-) Chronic Hepatitis B
• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis B; Hepatitis; Hepatitis B, Chronic; Hepatitis, Chronic; Anti-Infective Agents; Antiviral Agents; Entecavir; Clevudine
• Other Study ID Numbers: CLV-410