ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01379508
Recruitment Status : Completed
First Posted : June 23, 2011
Results First Posted : November 5, 2018
Last Update Posted : November 5, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
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 or disease Intervention/treatment Phase
Chronic Hepatitis B Drug: telbivudine Drug: tenofovir disoproxil fumarate Phase 4

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 241 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Actual Study Start Date : March 21, 2011
Actual Primary Completion Date : December 10, 2015
Actual Study Completion Date : December 10, 2015

Resource links provided by the National Library of Medicine


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 Name: 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




Primary Outcome Measures :
  1. Percentage of Participants Achieving HBV DNA < 300 Copies/mL (51 IU/mL) at Week 52 (rITT Population) - [ Time Frame: week 52 ]
    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."


Secondary Outcome Measures :
  1. Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT) [ Time Frame: week 24, 52, 104 ]
    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

  2. Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT) [ Time Frame: 156 weeks ]
    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

  3. eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study [ Time Frame: Baseline, 24 weeks, 52 weeks, 104 weeks, 156 weeks ]
    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.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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, 1413
Novartis Investigative Site
Sofia, Bulgaria, 1431
Novartis Investigative Site
Sofia, Bulgaria, 1527
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
Wurzburg, Germany, 97080
Greece
Novartis Investigative Site
Alexandroupolis, Evros, Greece, 681 00
Novartis Investigative Site
Athens, GR, Greece, 115 21
Novartis Investigative Site
Thessaloniki, GR, Greece, 546 42
Novartis Investigative Site
Athens, Greece, 115 27
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
Istanbul, TUR, Turkey, 34098
Novartis Investigative Site
Diyarbakir, Turkey, 21280
Novartis Investigative Site
Izmir, Turkey, 35040
Novartis Investigative Site
Trabzon, Turkey, 61080
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01379508     History of Changes
Other Study ID Numbers: CLDT600A2409
2007-000180-13 ( Registry Identifier: Eudract )
First Posted: June 23, 2011    Key Record Dates
Results First Posted: November 5, 2018
Last Update Posted: November 5, 2018
Last Verified: March 2018

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