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

OPTIMA: A Randomized, Open-label, 156-week Treatment Study to Evaluate the Efficacy and Safety of Telbivudine or Tenofovir Treatment in HBeAg-negative Chronic Hepatitis B Patients Based on the Roadmap Concept

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 Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: telbivudine; Drug: tenofovir disoproxil fumarate

• Study Type: Interventional
• Enrollment (Actual): 241
• Phase: Phase 4

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, A-6020
    • Novartis Investigative Site
  • Wien, Austria, 1090
    • Novartis Investigative Site
• Bulgaria
  • Sofia, Bulgaria, 1527
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1413
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1431
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1407
    • Novartis Investigative Site
  • Varna, Bulgaria, 9010
    • Novartis Investigative Site
• Germany
  • Frankfurt, Germany, 60590
    • Novartis Investigative Site
  • Freiburg, Germany, 79106
    • Novartis Investigative Site
  • Hamburg, Germany, 20099
    • Novartis Investigative Site
  • Hannover, Germany, 30625
    • Novartis Investigative Site
  • Herne, Germany, 44623
    • Novartis Investigative Site
  • Leipzig, Germany, 04103
    • Novartis Investigative Site
  • Wurzburg, Germany, 97080
    • Novartis Investigative Site
• Greece
  • Athens, Greece, 115 27
    • Novartis Investigative Site
  • Evros
    • Alexandroupolis, Evros, Greece, 681 00
      • Novartis Investigative Site
  • GR
    • Athens, GR, Greece, 115 21
      • Novartis Investigative Site
    • Thessaloniki, GR, Greece, 546 42
      • Novartis Investigative Site
• Italy
  • CE
    • Caserta, CE, Italy, 81100
      • Novartis Investigative Site
• Russian Federation
  • Moscow, Russian Federation
    • Novartis Investigative Site
  • Moscow, Russian Federation, 111123
    • Novartis Investigative Site
  • Moscow, Russian Federation, 119333
    • Novartis Investigative Site
  • Moscow, Russian Federation, 119992
    • Novartis Investigative Site
  • Moscow, Russian Federation, 127473
    • Novartis Investigative Site
  • Moscow, Russian Federation, 129110
    • Novartis Investigative Site
  • Saint-Petersburg, Russian Federation, 194044
    • Novartis Investigative Site
• Spain
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08003
      • Novartis Investigative Site
  • Cataluña
    • Tarragona, Cataluña, Spain, 43005
      • Novartis Investigative Site
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Novartis Investigative Site
• Turkey
  • Diyarbakir, Turkey, 21280
    • Novartis Investigative Site
  • Izmir, Turkey, 35040
    • Novartis Investigative Site
  • Trabzon, Turkey, 61080
    • Novartis Investigative Site
  • TUR
    • Istanbul, TUR, Turkey, 34098
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: telbivudine; telbivudine 600 mg tablet orally (p.o.) once daily for up to 156 weeks. Patients with HBV DNA ≥ 300 copies/mL at Week 24 were to initiate add-on therapy with tenofovir 300 mg tablets p.o. once daily for the remaining weeks of treatment. The investigator was to initiate tenofovir add-on therapy within 2 weeks of central laboratory confirmation. Patients with HBV DNA < 300 copies/mL at Week 24 were to continue to receive telbivudine monotherapy	Drug: telbivudine; 600 mg film-coated tablets taken as 600 mg once daily; Other Names: LDT600
Active Comparator: tenofovir; tenofovir 300 mg tablets p.o. once daily for up to 156 weeks. Patients with HBV DNA ≥ 300 copies/mL at Week 24 were to initiate add-on therapy with telbivudine 600 mg tablet p.o. once daily for the remaining weeks of treatment. The investigator was to initiate telbivudine add-on therapy within 2 weeks of central laboratory confirmation. Patients with HBV DNA < 300 copies/mL at Week 24 were to continue to receive tenofovir monotherapy	Drug: tenofovir disoproxil fumarate; 300 mg tablets taken as 300 mg once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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."	week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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.	Baseline, 24 weeks, 52 weeks, 104 weeks, 156 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2011
• Primary Completion (Actual): December 10, 2015
• Study Completion (Actual): December 10, 2015

Study Registration Dates

• First Submitted: June 21, 2011
• First Submitted That Met QC Criteria: June 22, 2011
• First Posted (Estimate): June 23, 2011

Study Record Updates

• Last Update Posted (Actual): November 5, 2018
• Last Update Submitted That Met QC Criteria: March 6, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Telbivudine
• Other Study ID Numbers: CLDT600A2409; 2007-000180-13 (Registry Identifier: Eudract)