Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

Telbivudine or Tenofovir Treatment in HBeAg-negative Chronic Hepatitis B Patients Based on the Roadmap Concept (Sebivo/Tyzeka)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01379508
First received: June 21, 2011
Last updated: April 20, 2016
Last verified: April 2016
  Purpose
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.

Condition Intervention Phase
Chronic Hepatitis B
Drug: Telbivudine 600mg
Drug: Tenofovir disoproxil fumarate 300mg
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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). [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • antiviral efficacy by the rate of patients achieving HBV DNA < 300 copies/ml at Week104, and at Week156 [ Time Frame: 104 weeks; 156 weeks ] [ Designated as safety issue: No ]
    To assess the antiviral efficacy, as evaluated by rate of patients achieving HBV DNA <300 copies/mL (51 IU/mL) at Week104, at Week156. In patients who achieve HBV DNA <300copies at Week 104, rate of patients with maintained HBV DNA <300 copies at Week 156

  • antiviral efficacy by serum HBV DNA reduction and time to achieve HBV DNA <300 copies/ml at Week104, and at Week156 [ Time Frame: over the course of the study ] [ Designated as safety issue: No ]
    To assess the antiviral efficacy, as evaluated by serum HBV DNA reduction from baseline, and time to achieve HBV DNA < 300 copies/mL (51 IU/mL). In patients who achive HBV DNA < 169 copies/ml at Week104, teh rate of patients with maintained HBV DNA <169 copies at Week156.

  • rate of HBsAg loss [ Time Frame: over the course of the study ] [ Designated as safety issue: No ]
    To assess the rate of HBsAg loss and HBsAg seroconversion (defined as loss of HBsAg and development of HBsAb) over the course of the study

  • biochemical efficacy [ Time Frame: Week 52; Week 104; Week 156 in patients with elevated ALT at baseline. ] [ Designated as safety issue: No ]
    To assess the biochemical efficacy as evaluated by rate of patients with ALT normalization

  • safety endpoint [ Time Frame: at Week 52, Week 104 and Week 156 ] [ Designated as safety issue: Yes ]
    To assess the safety endpoints as evaluated by incidence of death, AE, SAE, AESI and graded laboratory abnormalities

  • eGFR change in telbivudine arm vs tenofovir Arm over the course of the study [ Time Frame: 52 weeks, 104 weeks, 156 weeks ] [ Designated as safety issue: No ]
    eGFR changes from baseline to Week52, Week104 and Week156 for the overall population and sub-populations of patients with renal function impairment at baseline (eGFR 60-90 ml/min/1.73m2 or 60-80 ml/min/1.73m2). Percentage of patients with abnormal baseline eGFR shifting to normal eGFR at Week52, Week104 and Week156


Enrollment: 241
Study Start Date: March 2011
Study Completion Date: December 2015
Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 Drug: Telbivudine 600mg
Other Name: LDT600
Active Comparator: Arm 2 Drug: Tenofovir disoproxil fumarate 300mg

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01379508

Locations
Austria
Novartis Investigative Site
Innsbruck, Austria, A-6020
Novartis Investigative Site
Wien, Austria, 1090
Bulgaria
Novartis Investigative Site
Sofia, Bulgaria, 1407
Novartis Investigative Site
Sofia, Bulgaria, 1431
Novartis Investigative Site
Sofia, Bulgaria, 1527
Novartis Investigative Site
Sofia, Bulgaria, 1612
Novartis Investigative Site
Varna, Bulgaria, 9010
Germany
Novartis Investigative Site
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
Würzburg, Germany, 97080
Greece
Novartis Investigative Site
Alexandroupolis, Evros, Greece, 68100
Novartis Investigative Site
Athens, GR, Greece, 115 21
Novartis Investigative Site
Thessaloniki, GR, Greece, 546 39
Novartis Investigative Site
Athens, Greece, GR 11527
Italy
Novartis Investigative Site
Caserta, CE, Italy, 81100
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
Moscow, Russian Federation
Novartis Investigative Site
Saint-Petersburg, Russian Federation, 194044
Spain
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08003
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site
Tarragona, Cataluña, Spain, 43005
Novartis Investigative Site
Majadahonda, Madrid, Spain, 28222
Turkey
Novartis Investigative Site
Diyarbakir, Turkey, 21280
Novartis Investigative Site
Fatih / Istanbul, Turkey, 34098
Novartis Investigative Site
Izmir, Turkey, 35040
Novartis Investigative Site
Trabzon, Turkey, 61080
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01379508     History of Changes
Other Study ID Numbers: CLDT600A2409  2007-000180-13 
Study First Received: June 21, 2011
Last Updated: April 20, 2016
Health Authority: Europe: European Medicines Agency

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Tenofovir
Telbivudine
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents

ClinicalTrials.gov processed this record on September 28, 2016