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

Back to results

Primary Purpose

Status

Completed

Phase

Phase 4

Locations

International

Study Type

Interventional

Intervention

telbivudine

tenofovir disoproxil fumarate

About this trial

This is an interventional treatment trial for Chronic Hepatitis B

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

telbivudine

tenofovir

Arm Description

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

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

Outcomes

Primary Outcome Measures

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."

Secondary Outcome Measures

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

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

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.

Full Information

NCT ID

NCT01379508

First Posted

June 21, 2011

Last Updated

March 6, 2018

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01379508

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2018

Overall Recruitment Status

Completed

Study Start Date

March 21, 2011 (Actual)

Primary Completion Date

December 10, 2015 (Actual)

Study Completion Date

December 10, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee

No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Hepatitis B

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

241 (Actual)

8. Arms, Groups, and Interventions

Arm Title

telbivudine

Arm Type

Experimental

Arm Description

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

Arm Title

tenofovir

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

telbivudine

Other Intervention Name(s)

LDT600

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

tenofovir disoproxil fumarate

Intervention Description

300 mg tablets taken as 300 mg once daily

Primary Outcome Measure Information:

Title

Percentage of Participants Achieving HBV DNA < 300 Copies/mL (51 IU/mL) at Week 52 (rITT Population) -

Description

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."

Time Frame

week 52

Secondary Outcome Measure Information:

Title

Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)

Description

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

Time Frame

week 24, 52, 104

Title

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

Description

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

Time Frame

156 weeks

Title

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

Description

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.

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Innsbruck

ZIP/Postal Code

A-6020

Country

Austria

Facility Name

Novartis Investigative Site

City

Wien

ZIP/Postal Code

1090

Country

Austria

Facility Name

Novartis Investigative Site

City

Sofia

ZIP/Postal Code

1407

Country

Bulgaria

Facility Name

Novartis Investigative Site

City

Sofia

ZIP/Postal Code

1413

Country

Bulgaria

Facility Name

Novartis Investigative Site

City

Sofia

ZIP/Postal Code

1431

Country

Bulgaria

Facility Name

Novartis Investigative Site

City

Sofia

ZIP/Postal Code

1527

Country

Bulgaria

Facility Name

Novartis Investigative Site

City

Varna

ZIP/Postal Code

9010

Country

Bulgaria

Facility Name

Novartis Investigative Site

City

Frankfurt

ZIP/Postal Code

60590

Country

Germany

Facility Name

Novartis Investigative Site

City

Freiburg

ZIP/Postal Code

79106

Country

Germany

Facility Name

Novartis Investigative Site

City

Hamburg

ZIP/Postal Code

20099

Country

Germany

Facility Name

Novartis Investigative Site

City

Hannover

ZIP/Postal Code

30625

Country

Germany

Facility Name

Novartis Investigative Site

City

Herne

ZIP/Postal Code

44623

Country

Germany

Facility Name

Novartis Investigative Site

City

Leipzig

ZIP/Postal Code

04103

Country

Germany

Facility Name

Novartis Investigative Site

City

Wurzburg

ZIP/Postal Code

97080

Country

Germany

Facility Name

Novartis Investigative Site

City

Alexandroupolis

State/Province

Evros

ZIP/Postal Code

681 00

Country

Greece

Facility Name

Novartis Investigative Site

City

Athens

State/Province

GR

ZIP/Postal Code

115 21

Country

Greece

Facility Name

Novartis Investigative Site

City

Thessaloniki

State/Province

GR

ZIP/Postal Code

546 42

Country

Greece

Facility Name

Novartis Investigative Site

City

Athens

ZIP/Postal Code

115 27

Country

Greece

Facility Name

Novartis Investigative Site

City

Caserta

State/Province

CE

ZIP/Postal Code

81100

Country

Italy

Facility Name

Novartis Investigative Site

City

Moscow

ZIP/Postal Code

111123

Country

Russian Federation

Facility Name

Novartis Investigative Site

City

Moscow

ZIP/Postal Code

119333

Country

Russian Federation

Facility Name

Novartis Investigative Site

City

Moscow

ZIP/Postal Code

119992

Country

Russian Federation

Facility Name

Novartis Investigative Site

City

Moscow

ZIP/Postal Code

127473

Country

Russian Federation

Facility Name

Novartis Investigative Site

City

Moscow

ZIP/Postal Code

129110

Country

Russian Federation

Facility Name

Novartis Investigative Site

City

Moscow

Country

Russian Federation

Facility Name

Novartis Investigative Site

City

Saint-Petersburg

ZIP/Postal Code

194044

Country

Russian Federation

Facility Name

Novartis Investigative Site

City

Barcelona

State/Province

Catalunya

ZIP/Postal Code

08003

Country

Spain

Facility Name

Novartis Investigative Site

City

Barcelona

State/Province

Catalunya

ZIP/Postal Code

08035

Country

Spain

Facility Name

Novartis Investigative Site

City

Tarragona

State/Province

Cataluña

ZIP/Postal Code

43005

Country

Spain

Facility Name

Novartis Investigative Site

City

Majadahonda

State/Province

Madrid

ZIP/Postal Code

28222

Country

Spain

Facility Name

Novartis Investigative Site

City

Istanbul

State/Province

TUR

ZIP/Postal Code

34098

Country

Turkey

Facility Name

Novartis Investigative Site

City

Diyarbakir

ZIP/Postal Code

21280

Country

Turkey

Facility Name

Novartis Investigative Site

City

Izmir

ZIP/Postal Code

35040

Country

Turkey

Facility Name

Novartis Investigative Site

City

Trabzon

ZIP/Postal Code

61080

Country

Turkey

Chronic Hepatitis B

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial