Entecavir for Chronic Hepatitis B Patients With Persistently Normal ALT

NCT01833611 | Unknown Phase 4 DMC

• 1 other identifier: ETV HR-96-23
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 4

Brief Summary

Entecavir (ETV) has shown superior ability to suppress hepatitis B virus (HBV) replication, histology improvement as well as low rate of emergence of resistant mutants. Out of range of clinical recommendations for treatment of chronic hepatitis B (CHB), chronic HBV carriers with persistently normal ALT and viral load more than 10\^5 copies/mL have progression of liver disease during long-term follow-up. In addition, certain proportions of these patients do have significant inflammation and fibrosis in liver histology. This study will be able to identify who are at risk of liver disease progression and evaluate efficacy of ETV regarding improvement of liver histology during short-term (1-year) and long-term ETV treatment (3-year).

Conditions

Chronic Hepatitis

Outcome Measures

Primary Outcomes (1)

• Improvement of liver histology in patients with chronic hepatitis B virus infection and persistently normal ALT receiving entecavir. Please refer to "Description" section for the definiton of improvement of liver histology

  1. The ratio of liver histology improvement in two groups. 2. Definition of improving liver histology is improvement in the necroinflammatory score (≥ 2 point decrease in Knodell necroinflammation score) and no worsening of fibrosis (≥ 1 point increase in the Knodell fibrosis score) at the week 52 liver biopsy compared to baseline.

  1 year

Secondary Outcomes (2)

• Undetectable HBV DNA

  1 year and 3 year

• the reduction of HBV DNA from baseline

  1 year and 3 year

Study Arms (2)

ETV group

EXPERIMENTAL

Entecavir 0.5mg at first year; then open with entecavir 0.5mg qd for 2nd, 3rd year

Drug: Entecavir

Placebo group

PLACEBO COMPARATOR

Placebo at first year, then opne with entecavir 0.5mg qd for 2nd, 3rd year

Drug: placebo

Interventions

Entecavir DRUG

entecavir 0.5mg qd

Also known as: baraclude (generic name)

ETV group

placebo DRUG

placebo qd

Placebo group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects aged between 18 and 65 year-old with history of chronic hepatitis B virus infection;
• Detectable HBsAg at screening and for at least 24 weeks prior to screening or detectable HBsAg for \< 24 week and negative for IgM core antibody and confirmation of chronic hepatitis on liver biopsy;
• ALT should be within normal range in recent one year and at least twice, which are at least 3 month apart;
• Normal ALT at screening;
• Screening HBV DNA of more than 10\^5 copies/mL by Roche AmplicorTM PCR assay performed by the central laboratory;
• Evidence of chronic hepatitis on liver biopsy (Knodell HAI Score \>= 4) performed ≤ 52 weeks prior to randomization;
• All women of childbearing potential must have a negative serum or urine pregnancy test.

You may not qualify if:

• Coinfection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis D virus (HDV);
• Other forms of liver disease e.g., alcoholic, autoimmune, biliary disease;
• Patients with evidence of decompensation of liver disease;
• Therapy with interferon, thymosin alpha or antiviral agents with activity against hepatitis B (e.g., adefovir, famciclovir, lamivudine, and telbivudine) within 24 weeks of randomization into this study;
• More than 12 weeks of prior therapy with nucleoside or nucleotide analogue antiviral agents with activity against hepatitis B (e.g., adefovir, famciclovir lamivudine, and telbivudine);
• Prior therapy with entecavir;
• Known history of allergy to nucleoside analogues;
• Hemoglobin \< 10.0 g/dL;
• Platelet count \< 75,000/mm3;
• Absolute neutrophil count\< 1500 cells/mm3;
• Creatinine \> 1.5mg/dL (133 μmol/L);
• Anti-nuclear antibody (ANA) titer \> l :160 unless attributable to non-hepatic disease.

Sponsors & Collaborators

• National Cheng-Kung University Hospital: lead

Study Sites (4)

Buddhist Dalin Tzu-Chi General Hospital

Chiayi City, Taiwan

Location

Chia-Yi Christian Hospital

Chiayi City, Taiwan

Location

Chang-Gung Memorial Hospital, Kaohsiung

Kaohsiung City, Taiwan

Location

Kaohsiung Medical University Hospital

Kaohsiung City, Taiwan

Location

Related Publications (1)

• Tseng KC, Chen CY, Tsai HW, Chang TT, Chuang WL, Hsu PI, Liu WC, Cheng PN. Efficacy of entecavir in chronic hepatitis B patients with persistently normal alanine aminotransferase: randomized, double-blind, placebo-controlled study. Antivir Ther. 2014;19(8):755-64. doi: 10.3851/IMP2754. Epub 2014 Feb 28.

  PMID: 24583931 DERIVED

MeSH Terms

Conditions

Hepatitis, Chronic

Interventions

entecavir

Condition Hierarchy (Ancestors)

Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ting-Tsung Chang, MD. PhD

  National Cheng-Kung University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: April 27, 2012
• First Posted: April 17, 2013
• Study Start: September 1, 2008
• Primary Completion: November 1, 2014
• Study Completion: May 1, 2015
• Last Updated: April 17, 2013

Record last verified: 2013-04

Locations

TW (4)