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

• 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: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

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 Design

• 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

Arms and Interventions

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

Outcome Measures

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.

Eligibility Criteria

• 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

Contacts and Locations

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

More Information

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

Additional relevant MeSH terms:

Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Infections; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Blood-Borne Infections; Communicable Diseases; 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-HIV Agents; Anti-Retroviral Agents