Effectiveness of Nucleos(t)Ide Analogs (NUC) Therapy Among Naive CHB Patients in China

Study Overview
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Brief Summary
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To compare the effectiveness, in a real world practice setting in tier 2 cities of China, of Entecavir (ETV) monotherapy and Lamivudine (LAM) based therapies (including LAM monotherapy, de novo LAM + Adefovir [ADV] combination, and early add-on of ADV) among chronic hepatitis B (CHB) patients who are naive to NUC at enrollment to this study

Detailed Description
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Sampling Method: Consecutive patient sampling Biospecimen Retention: Blood samples for HBV viral load testing along the treatment period of this study

Official Title
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A 5-year Prospective and Observational Study to Evaluate the Effectiveness of Nucleos(t)Ide Analogs (NUC) Therapy Among Chronic Hepatitis B (CHB) Patients Naive to NUC in Real World Practice at Hospitals in Tier 2 Cities in China (the EVOLVE Study)

Conditions
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Chronic Hepatitis B

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CHB patients, or CHB patients with compensated cirrhosis, as defined by the current Chinese guidelines Male or female ≥ 18 years of age Either Hepatitis B e antigen (HBeAg) positive or negative Naïve to NUC (defined as no previous exposure to NUC treatment as based on patient self-report) Has compensated liver disease Patients with compensated cirrhosis Patients who consent to participate in this study Local residents with medical reimbursement coverage preferred Exclusion Criteria: Co-infected with hepatitis C virus (HCV) CHB patients with decompensated cirrhosis, liver failure, hepatocellular carcinoma, or any other types of malignancy at the screening phase CHB patients who are being treated by interferon therapy within 6 months immediately prior to the screening phase of this study CHB patients with a confirmed pregnancy

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CHB patients who are naive to NUC treatment<br>CHB patients who are naive to NUC at enrollment and be treated at hospitals at tier 2 cities in China | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who achieve virology response (defined as HBV DNA < 300 copies/mL) by ETV monotherapy in comparison with LAM-based therapy | Virology response is defined as Hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) < 300 copies/mL by a highly sensitive assay such as Roche COBAS or Abbott Real Time Polymerase chain reaction (PCR) performed in a one central laboratory | 48 weeks after initial NUC antiviral therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean HBV DNA reductions after 48 weeks of treatment from baseline for ETV and LAM-based therapy patients (stratifying by the 3 LAM-based subgroups) |  | Baseline (Day 1) and 48 weeks | 
| Proportion of patients who achieve virology response by ETV in comparison with LAM-based therapy after 24 weeks and 96 weeks of treatment (stratifying by the 3 LAM based subgroups) |  | 24 weeks and 96 weeks | 
| Proportion of patients who modify their initial treatment options to manage suboptimal response or resistance after 24 weeks, 48 weeks, and 96 weeks of treatment among all treatment options |  | 24 weeks, 48 weeks and 96 weeks | 
| Proportion of patients who achieve virology response among other treatment options, including ADV, LdT, and combinations of NUCs, after 24 weeks, 48 weeks, 72 weeks, 96 weeks, 144 weeks, 192 weeks and 240 weeks of treatment | HBV DNA levels at week 24 will be analyzed at the laboratories of hospitals where the patients are treated while evaluation of HBV DNA levels after 48 and 96 weeks of treatment will be conducted at the central laboratory | 24 weeks, 48 weeks, 72 weeks, 96 weeks, 144 weeks, 192 weeks and 240 weeks | 
| Cumulative incidence of patients who develop viral breakthrough and/or genotypic resistance |  | 24 weeks, 48 weeks, 72 weeks, 96 weeks, 144 weeks, 192 weeks and 240 weeks | 
| Cumulative incidence of clinical outcome (eg, HCC, death, decompensated cirrhosis) in ETV arm versus LAM-based and other treatment arms |  | 48 weeks, 96 weeks, 144 weeks, 192 weeks and 240 weeks |