Telbivudine Versus Lamivudine in Adults With Decompensated Chronic Hepatitis B and Evidence of Cirrhosis

Study Overview
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Brief Summary
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This research study was conducted to compare the safety and effectiveness of the investigational medication, LdT (Telbivudine) versus Lamivudine, a drug currently approved by the US, European and Asian Health Authorities for the treatment of Hepatitis B infection. The results for patients taking LdT will be compared to results for patients taking lamivudine.

Detailed Description
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Multicenter, multinational, randomized, double-blind study designed to compare the safety and efficacy of telbivudine (600 mg/day) versus lamivudine (100 mg/day) for 104 weeks in adults with decompensated chronic hepatitis B and evidence of cirrhosis. Patients were pre-stratified by screening Child-Turcotte-Pugh score (CTP score < 9 or ≥ 9) and ALT level (within normal limits (WNL) or > 1.0 x ULN) to help assure similar degrees of hepatic insufficiency and liver inflammation on both treatment arms. After 104 weeks of treatment, participants were followed-up with for an additional 16 weeks.

Official Title
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Randomized, Double-Blind Trial of Telbivudine Versus Lamivudine in Adults With Decompensated Chronic Hepatitis B and Evidence of Cirrhosis

Conditions
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Hepatitis, Hepatitis B, Chronic, Cirrhosis

Intervention / Treatment
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* Drug: Telbivudine
* Drug: Lamivudine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented decompensated chronic hepatitis B defined by all of the following: 1. Clinical history compatible with decompensated chronic hepatitis B related cirrhosis; 2. Child-Turcotte-Pugh score > 7 points. Evidence of hepatic cirrhosis or portal hypertension. Other protocol-defined inclusion criteria may apply. Exclusion Criteria: Patient is pregnant or breastfeeding. Patient is coinfected with hepatitis C virus (HCV), hepatitis D virus (HDV), or Human immunodeficiency virus (HIV). Patient previously received lamivudine, adefovir, or an investigational anti-hepatitis B virus (HBV) nucleoside or nucleotide analog at any time Patient has received interferon or other immunomodulatory treatment for HBV infection 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: 16 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telbivudine 600 mg<br>Participants received Telbivudine 600 mg and a matching lamivudine placebo orally once a day for up to 104 weeks. Participants were followed-up for 16 weeks post-treatment. | Drug: Telbivudine<br>* 600mg/day oral tablet for 104 weeks<br>* Other names: LDT600;Drug: Placebo<br>* Telbivudine matching placebo or lamivudine matching placebo tablet.<br>|
| Active Comparator: Lamivudine 100 mg<br>Lamivudine 100 mg and a Telbivudine matching placebo orally once a day for up to 104 weeks. Participants were followed-up for 16 weeks post-treatment. | Drug: Lamivudine<br>* 100mg/day oral tablet for 104 weeks<br>Drug: Placebo<br>* Telbivudine matching placebo or lamivudine matching placebo tablet.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinical Response | Clinical response defined as achieving all of the following 3 criteria on at least 2 consecutive visits or at the last on-treatment visit: Serum hepatitis B virus (HBV) DNA < 4 log10 copies/mL, normal Alanine transaminase (ALT) level (ALT ≤ Upper Limit of Normal (ULN)), and improvement (a 2- point or greater reduction in Child-Turcotte-Pugh (CTP) score) or stabilization (not more than a 1-point change in CTP score), compared to the baseline value. CTP scores range from 5-15, higher scores indicate more liver impairment. For Improvement/Stabilization, either of the individual criteria were met. | From Baseline to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Initial Clinical Response | Time to Clinical Response defined as the number of days elapsed from the baseline visit to achieving initial Clinical Response. | From Baseline to Week 104 | 
| Duration of Initial Clinical Response | Kaplan-Meier method was used. The duration was calculated as: date of last visit before initial loss of clinical response - date of initial clinical response occurred+1. If a patient did not lose clinical response, it was then censored at the efficacy overall censoring date. | Baseline to Week 104 | 
| Number of Participants With Improvement, Stabilization, and Worsening in Child-Turcotte-Pugh (CTP) Score at Week 52 and Week 104 | Child-Turcotte-Pugh (CTP) uses 2 clinical variables, ascites and encephalopathy, and 3 laboratory parameters, serum bilirubin, albumin, and prothrombin time. Each variable is assigned a score from 1 to 3, with the combined score comprising the CTP score range of 5 to 15 points. Higher scores indicate more impaired liver function. Worsening of CTP score was defined as a 2-point or greater increase from baseline, improvement in CTP score was defined as a 2-point or greater reduction from baseline, and stabilization of CTP score was defined as a change of 1-point or less from baseline. | From Baseline to weeks 52 and 104 | 
| Number of Participants With Improvement, Stabilization, and Worsening in a Modified (3-component) CTP Score | Modified CTP was calculated using the 3 biochemical-components (serum bilirubin, albumin, and prothrombin). Total scores range from 3-9; higher scores indicate more liver impairment. Improvement was defined as 2-point or greater reduction in score from baseline. Stabilization comprises a score change of 1-point or less from baseline. Worsening of CTP score was defined as a 2-point or greater increase from baseline. The rationale for assessing changes in this modified (3-component) CTP score is that this maneuver removed the two subjective components of CTP scoring (ascites and encephalopathy). | Baseline and Week 104 |