Telbivudine or Tenofovir Treatment in HBeAg-negative Chronic Hepatitis B Patients Based on the Roadmap Concept

Novartis Pharmaceuticals241 enrolled

Overview

The purpose of this study is to evaluate the efficacy and safety following the Roadmap Concept strategy with an initial monotherapy using either telbivudine or tenofovir in HBeAg negative CHB patients. The data from the study should allow for the validation of the Roadmap concept in a prospective manner, for both telbivudine and tenofovir treated HBeAg negative CHB patients. As part of a post-approval commitment to the European Health Authorities, the data will also be used to provide an optimized clinical treatment strategy for better clinical use of telbivudine in European HBeAg negative patients. Furthermore, the data from the study will contribute to a better scientific understanding, disease management and treatment of HBeAg negative CHB patients.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

241

Conditions

Chronic Hepatitis B

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: Male or female, at least 18 years of age Documented compensated HBeAg negative CHB defined by all of the following: * Detectable serum HBsAg at screening visit and at least 6 months prior; * HBeAg negative at the screening visit with positive HBeAb; * Serum HBV DNA \> 2000 IU/mL Serum ALT level \> 1×ULN and \<10×ULN at screening visit; patient with normal ALT ≤1xULN at screening are eligible, with moderate liver inflammation or fibrosis, complensated liver sirrhosis, ALT level \>1xULN wtihin last 6 months Exclusion Criteria: * Co-infected with HCV, HDV or HIV. * Received treatment of nucleoside or nucleotide drugs at any time * Received IFN or other immunomodulatory treatment within six months before Screening * Pregnant or nursing (lactating) women * Clinical signs/symptoms of hepatic decompensation * History of myopathy, myositis or persistent muscle weakness * history of clinical and laboratory evidence of chronic renal insufficency

Locations (34)

Novartis Investigative Site

Innsbruck, Austria

Novartis Investigative Site

Vienna, Austria

Novartis Investigative Site

Sofia, Bulgaria

Novartis Investigative Site

Sofia, Bulgaria

Novartis Investigative Site

Sofia, Bulgaria

Novartis Investigative Site

Outcomes

Primary Outcomes

Percentage of Participants Achieving HBV DNA < 300 Copies/mL (51 IU/mL) at Week 52 (rITT Population) -

The primary objective of the study is to compare the efficacy of Roadmap-Concept-based telbivudine treatment versus Roadmap-Concept-based tenofovir treatment in HBeAg-negative CHB patients. The rate of HBV DNA \< 300 copies/mL (51 IU/mL) at week 52 will be used for the comparison of the efficacy. The hypothesis is that the aggregated rate of HBV DNA \< 300 copies/mL (51 IU/mL) at week 52 of Telbivudine (ARM 1) is non-inferior to Tenofovir (ARM 2). For the "treating missing as failure" analysis, patients who came for their primary endpoint Week 52 visit within the ± 7-day window but not on the exact designated day of the visit were treated as "missing data."

Time frame: week 52

Secondary Outcomes

Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)

To assess the antiviral efficacy, as evaluated by the percentage of patients achieving HBV DNA \<300 copies/mL (51 IU/mL), ALT normalization, HBsAg loss, HBsAg conversion, virologic breakthrough (VB) at study visit, cumulative VB by study defined study period, cumulative treatment-emergent resistance

Time frame: week 24, 52, 104

Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT)

To assess the antiviral efficacy, as evaluated by the percentage of patients achieving HBV DNA \<300 copies/mL (51 IU/mL) at Week156, ALT normalization, HBsAg loss, development of HBsAg conversion , cumulative tx emergent resistance, HBV DNA \<300 copies/mL with HBV DNA \<7 log at Baseline

Time frame: 156 weeks

eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study

eGFR changes were calculated using the Modification of Diet in Renal Disease (MDRD) formula: GFR = 186 x (sCr)\^(-1.154) x (age)\^-0.203 with Female: Multiply GFR by 0.742; Black: Multiply GFR by 1.210. sCr is Serum Creatinine in mg/dl (measured at each scheduled visit). Age in years at visit (=\[sCr sample collection date -Date of birth\]/365.25). Weight in kilograms, as measured at the visit or the closest previous visit Safety population.

Time frame: Baseline, 24 weeks, 52 weeks, 104 weeks, 156 weeks