Viral Kinetics Study of Telbivudine and Entecavir in Adults With Chronic Hepatitis B

Study Overview
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Brief Summary
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This exploratory study is designed to determine the early viral kinetic profile during treatment with telbivudine or entecavir at multiple time points over 12 weeks.

Official Title
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A Randomized, Open-label, Controlled, Multicenter, Exploratory Trial to Characterize the Results of Daily Oral Administration of Telbivudine (LDT600) 600 mg or Entecavir (ETV) 0.5 mg Given Over 12 Weeks on the Kinetics of Hepatitis B Virus (HBV) DNA in Adults With HBeAg-positive, Compensated Chronic Hepatitis B (CHB)

Conditions
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Hepatitis B, Chronic Hepatitis B

Intervention / Treatment
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* Drug: Entecavir
* Drug: Telbivudine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18-70 years of age with documented compensated hepatitis B e antigen (HBeAg)-positive chronic hepatitis B Able to comply with study regimen and provide written informed consent Exclusion Criteria: Pregnant or breastfeeding Unwilling to use double barrier method of contraception Co-infected with hepatitis C virus (HCV), hepatitis D virus (HDV) or human immunodeficiency virus (HIV) Received Hepatitis B therapy in the past Use of immunomodulatory therapy in past 12 months History of or symptoms of hepatic decompensation or pancreatitis Frequent or prolonged use of potentially hepatotoxic or nephrotoxic drugs Concurrent medication likely to preclude compliance with schedule of evaluations Use of other investigational drugs within 30 days of enrollment Abnormal laboratory values during screening Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telbivudine<br> | Drug: Telbivudine<br>* Telbivudine 600 mg once daily for 12 weeks.<br>|
| Active Comparator: Entecavir<br> | Drug: Entecavir<br>* Entecavir 0.5 mg once daily for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean Hepatitis B Virus (HBV) DNA Levels | Baseline HBV DNA is defined as the last pre-dose assessment of HBV DNA. | Baseline (day 1) to Week 12 (day 85) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean HBV DNA Level | Baseline HBV DNA is defined as the last pre-dose assessment of HBV DNA.HBV DNA reductions, considered as the repeated measures, from baseline to Weeks 2, 4, 8. | Baseline (day 1) to Weeks 2, 4, 8 | 
| The Area Under the Curve (AUC) of HBV DNA Change. | In AUC efficacy analyses, all the visits from baseline to Week 12 visit (including the planned and the repeated) with a non-missing HBV DNA level were included. | From Baseline to Week 12 | 
| Change in Alanine Aminotransferase (ALT) Levels |  | From Baseline to Week 12 | 
| Characterization of Very Early Viral Kinetics: Estimation of Viral Clearance | Viral kinetic parameters were estimated with a bi-phasic mathematical model: V(t) = (1-ε)pI(t) - cV(t) I(t) = (1- η)TV(t) - δI(t) V serum viral load, I productively infected cells, ε efficiency factor of blocking virus production, p viral production rate, c viral clearance rate, η efficiency factor of blocking de novo infection, β de novo infection rate, T uninfected target cells, δ rate of infected cell loss. Maximum-likelihood estimation for the viral kinetic parameters entailed fitting a nonlinear differential equation system via the least-squares approach from serum HBV DNA data. | Baseline to 12 weeks | 
| Characterization of Very Early Viral Kinetics: Estimation of the Rate of Infected Cell Loss | Viral kinetic parameters were estimated with a bi-phasic mathematical model: V(t) = (1-ε)pI(t) - cV(t) I(t) = (1- η)TV(t) - δI(t) V serum viral load, I productively infected cells, ε efficiency factor of blocking virus production, p viral production rate, c viral clearance rate, η efficiency factor of blocking de novo infection, β de novo infection rate, T uninfected target cells, δ rate of infected cell loss. Maximum-likelihood estimation for the viral kinetic parameters entailed fitting a nonlinear differential equation system via the least-squares approach from serum HBV DNA data. | Baseline to 12 weeks | 
| Characterization of Very Early Viral Kinetics: Estimation of the Efficiency Factor of Blocking Virus Production | Viral kinetic parameters were estimated with a bi-phasic mathematical model of HBV DNA by using compartments of free virus, infected cells, and uninfected target cells. The model parameter of interest was the effectiveness of the drug in blocking virus production from infected cells (efficacy, ε). Blocking efficiency was within the range between 0 and 1. | Baseline to 12 weeks | 
| Number of Patients Who Are Polymerase Chain Reaction (PCR) Negative | PCR negative was considered <300 copies/mL. PCR positive was considered =>300 copies/mL. | At Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HBeAg-positive, chronic hepatitis B, telbivudine, entecavir, viral kinetics