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

NCT01379508 | Completed Phase 4 Results

• 2 other identifiers: CLDT600A24092007-000180-13
• Study Type: interventional
• Target: 241
• Locations: 8 countries
• Sites: 34

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.

Conditions

Chronic Hepatitis B

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)

  week 24, 52, 104

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

  156 weeks

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

  Baseline, 24 weeks, 52 weeks, 104 weeks, 156 weeks

Study Arms (2)

telbivudine

EXPERIMENTAL

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

tenofovir

ACTIVE COMPARATOR

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

Interventions

telbivudine DRUG

600 mg film-coated tablets taken as 600 mg once daily

Also known as: LDT600

telbivudine

tenofovir disoproxil fumarate DRUG

300 mg tablets taken as 300 mg once daily

tenofovir

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (34)

Novartis Investigative Site

Innsbruck, A-6020, Austria

Location

Novartis Investigative Site

Vienna, 1090, Austria

Location

Novartis Investigative Site

Sofia, 1407, Bulgaria

Location

Novartis Investigative Site

Sofia, 1413, Bulgaria

Location

Novartis Investigative Site

Sofia, 1431, Bulgaria

Location

Novartis Investigative Site

Sofia, 1527, Bulgaria

Location

Novartis Investigative Site

Varna, 9010, Bulgaria

Location

Novartis Investigative Site

Frankfurt, 60590, Germany

Location

Novartis Investigative Site

Freiburg im Breisgau, 79106, Germany

Location

Novartis Investigative Site

Hamburg, 20099, Germany

Location

Novartis Investigative Site

Hanover, 30625, Germany

Location

Novartis Investigative Site

Herne, 44623, Germany

Location

Novartis Investigative Site

Leipzig, 04103, Germany

Location

Novartis Investigative Site

Würzburg, 97080, Germany

Location

Novartis Investigative Site

Alexandroupoli, Evros, 681 00, Greece

Location

Novartis Investigative Site

Athens, GR, 115 21, Greece

Location

Novartis Investigative Site

Thessaloniki, GR, 546 42, Greece

Location

Novartis Investigative Site

Athens, 115 27, Greece

Location

Novartis Investigative Site

Caserta, CE, 81100, Italy

Location

Novartis Investigative Site

Moscow, 111123, Russia

Location

Novartis Investigative Site

Moscow, 119333, Russia

Location

Novartis Investigative Site

Moscow, 119992, Russia

Location

Novartis Investigative Site

Moscow, 127473, Russia

Location

Novartis Investigative Site

Moscow, 129110, Russia

Location

Novartis Investigative Site

Moscow, Russia

Location

Novartis Investigative Site

Saint Petersburg, 194044, Russia

Location

Novartis Investigative Site

Barcelona, Catalonia, 08003, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Tarragona, Catalonia, 43005, Spain

Location

Novartis Investigative Site

Majadahonda, Madrid, 28222, Spain

Location

Novartis Investigative Site

Istanbul, TUR, 34098, Turkey (Türkiye)

Location

Novartis Investigative Site

Diyarbakır, 21280, Turkey (Türkiye)

Location

Novartis Investigative Site

Izmir, 35040, Turkey (Türkiye)

Location

Novartis Investigative Site

Trabzon, 61080, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

Telbivudine; Tenofovir

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Clinical Disclosure Office
• Organization: Novartis

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2011
• First Posted: June 23, 2011
• Study Start: March 21, 2011
• Primary Completion: December 10, 2015
• Study Completion: December 10, 2015
• Last Updated: November 5, 2018
• Results First Posted: November 5, 2018

Record last verified: 2018-03

Locations

TU (4); IT (1); RU (7); AU (2); BU (5); GR (4); DE (7); ES (4)