Study of Combination Therapy With LdT Plus Adefovir Versus Adefovir Alone

Study Overview
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Brief Summary
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This study is being conducted to compare the safety and effectiveness of the investigational medication LdT (telbivudine) used in combination with adefovir dipivoxil (a drug currently approved by the Food and Drug Administration [FDA] for the treatment of hepatitis B virus [HBV]) versus adefovir dipivoxil used alone. The results for patients taking the combination therapy will be compared to the results for patients taking adefovir alone.

Official Title
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An Open-label, Multicenter, Randomized Study of Combination Therapy With Oral LDT600 (Telbivudine) Plus Adefovir Dipivoxil Versus Adefovir Dipivoxil Alone in HBeAg-positive Patients With Chronic Hepatitis B Who Are Lamivudine Resistant

Conditions
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Hepatitis B

Intervention / Treatment
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* Drug: telbivudine
* Drug: adefovir dipivoxil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented compensated chronic hepatitis B defined by a clinical history compatible with chronic hepatitis B. Previous or current lamivudine treatment HBV DNA > 6 log10 copies/mL Evidence of viral breakthrough Other protocol-defined inclusion criteria may apply. Exclusion Criteria: Patient is pregnant or breastfeeding. Patient is co-infected with hepatitis C virus (HCV), hepatitis D virus (HDV), or HIV. Patient has received any anti-HBV treatment for HBV infection other than lamivudine in the 12 months before Screening for this study. Other protocol-defined 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: Combination therapy<br>Combination therapy: 600 mg of telbivudine (LdT) by mouth plus 10 mg of adefovir (ADV) by mouth once daily for 96 weeks. | Drug: telbivudine<br>* 600mg/day oral tablet for 96 weeks<br>Drug: adefovir dipivoxil<br>* 10 mg of adefovir by mouth once daily<br>|
| Active Comparator: Adefovir monotherapy<br>Adefovir monotherapy: 10 mg of adefovir by mouth once daily for 96 weeks. | Drug: adefovir dipivoxil<br>* 10 mg of adefovir by mouth once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Proportion of Participants Who Experienced Virologic Breakthrough | Virologic breakthrough is defined as a minimum of 1 log reduction from baseline followed by a 1 log increase from nadir on at least 2 consecutive visits including the last treatment visit. | 96 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Hepatitis B Virus (HBV) DNA Concentration | Efficacy was assessed by the change from baseline in mean HBV DNA concentration after 12, 24, 48 and 60 weeks of treatment. | Baseline to 12 weeks, 24 weeks, 48 weeks and 60 weeks | 
| Percentage of Participants Achieving Specified Clinical and Laboratory Safety Criteria | Undetectable HBV DNA = HBV DNA <300 copies/ml. Serum aminotransferase (ALT) normalization is defined as ALT within normal limits on 2 successive visits for a pt. with an elevated ALT level (>=1.0 x ULN) at baseline (BL). Hepatitis B e antigen (HBeAg) loss is defined as the loss of detectable serum HBeAg in a pt. who was HBeAg +ve at BL. HBeAg seroconversion is defined as HBeAg loss with detectable HBeAb. Hepatitis B surface antigen (HBsAg) loss is defined as the loss of detectable serum HBsAg in a pt. who was HBsAg +ve at BL. HBsAg seroconversion is defined as HBsAg loss with detectable HBsAb. | 12 week, 24 week, 48 week and 60 weeks | 
| Proportion of Participants With Treatment-emergent HBV Resistance Mutations Associated With Virologic Breakthrough | The study was not completed as planned and was terminated early with agreement from the European Medicines Agency (EMEA). Patients did not receive 96 weeks of treatment. Therefore, the primary objective of evaluating virologic breakthrough by Week 96 could not be assessed. Consequently, all protocol-specified inferential analyses on the primary endpoint and all other key secondary efficacy endpoints could not be performed. | Week 96 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lamivudine resistance, Hepatitis B virus