Efficacy and Safety of Telbivudine in Treatment naïve Patients With Hepatitis B e Antigen (HBeAg)-Positive Chronic Hepatitis B (CHB)

June 14, 2011 updated by: Novartis

A Randomized, Open-label, Controlled, Multi-center Two-year Study Comparing Efficacy and Safety of Telbivudine, 600 mg PO in Combination With Peginterferon Alpha-2a sq 180 µg With Peginterferon Alpha-2a Monotherapy, and With Telbivudine Monotherapy in Treatment naïve Patients With HBeAg-positive CHB.

To evaluate the combination of telbivudine 600 mg orally (PO) once daily and peginterferon alpha-2a 180 ug subcutaneous (sq) injection weekly for antiviral efficacy in comparison to peginterferon alpha-2a monotherapy.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
159

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94115
        • Novartis

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Documented Chronic hepatitis B (CHB) defined by all of the following:

  • Clinical history compatible with CHB
  • Detectable serum Hepatitis B Surface Antigen (HBsAg) at the Screening visit and at least 6 months prior
  • HBeAg-positive at the Screening visit
  • Hepatitis B 'e' Antibody (HBeAb)-negative at the Screening visit
  • History of evidence of chronic liver inflammation,
  • Elevated serum Alanine aminotransferase (ALT) level (1.3 - 10 x upper limit of normal (ULN)) at the Screening visit
  • Serum HBV DNA level ≥ 6 log10 copies/mL,
  • Chronic liver inflammation on previous liver biopsy within the previous 24 months.

Exclusion Criteria:

  • Co-infection with Hepatitis C Virus (HCV), Hepatitis D Virus (HDV), or Human Immunodeficiency Virus (HIV).

  • Has any of the following drug therapy:

    • Previously been treated in a trial with telbivudine
    • Received nucleoside or nucleotide therapy whether approved or investigational
    • Received any immunomodulatory treatment in the 12 months before Screening for this study.
    • Has a medical condition that required prolonged or frequent use of systemic acyclovir or famciclovir.
    • Has a medical condition that requires frequent or prolonged use of systemic corticosteroids although inhaled or intra-articular corticosteroids are allowed.
    • Has a medical condition requiring the chronic or prolonged use of potentially hepatotoxic drugs or nephrotoxic drugs.
    • Is currently abusing alcohol or illicit drugs or has a history of alcohol abuse illicit substance abuse within the preceding two years.
    • Uses other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer.
    • Is currently receiving methadone.

  • Patient has any of the following:

    • History of or clinical signs/symptoms of hepatic decompensation such as ascites, esophageal variceal bleeding, hepatic encephalopathy, or spontaneous bacterial peritonitis.
    • History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin. Patients with previous findings suggestive of possible HCC should have the disease ruled out prior to entrance into the study.
    • One or more additional known primary or secondary causes of liver disease other than hepatitis B, including steatohepatitis.
    • History of clinical and laboratory evidence of chronic pancreatitis, or demonstrates a clinical and laboratory course consistent with current pancreatitis.
  • Has laboratory values during screening visit not within normal limits.
  • Is pregnant or breastfeeding.
  • Is a women of child-bearing potential that is unwilling to practice birth control.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: LdT+ PEG-INF
Telbivudine (LdT) 600 mg orally once a day for 104 weeks in combination with peginterferon alpha-2a (PEG-INF)180 μg subcutaneous injection once a week for 52 weeks.
Drug: Telbivudine (LdT)
600 mg orally once daily for 104 weeks.
Other Names:
  • Sebivo
Drug: peginterferon alpha-2a
180 μg subcutaneous injection once a week for 52 weeks.
Other Names:
  • Pegasys
Experimental: LdT Monotherapy
Telbivudine (LdT) monotherapy: 600 mg orally once daily for 104 weeks.
Drug: Telbivudine (LdT)
600 mg orally once daily for 104 weeks.
Other Names:
  • Sebivo
Active Comparator: PEG-INF Monotherapy
Peginterferon alpha-2a (PEG- INF) monotherapy: 180 μg subcutaneous injection once a week for 52 weeks.
Drug: peginterferon alpha-2a
180 μg subcutaneous injection once a week for 52 weeks.
Other Names:
  • Pegasys

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants Who Achieved HBV DNA Non-detectability With Peginterferon Alpha-2a Plus Telbivudine Combination Therapy Versus Peginterferon Alpha-2a Monotherapy
Time Frame: At week 52
The original primary efficacy variable was the percentage of patients achieving HBV DNA non-detectability utilizing polymerase chain reaction (PCR) (threshold for detection 300 copies/mL); however, this analysis was not performed due to premature study termination.
At week 52
Percentage of Participants With HBV DNA Non-detectability and Alanine Aminotransferase (ALT) Normalization at Week 12 and Week 24 in Participants With HBeAg-positive Chronic Hepatitis B (CHB)
Time Frame: Weeks 12 and 24
The percentage of participants who achieved HBV DNA non-detectability using the COBAS Amplicor HBV Monitor assay utilizing polymerase chain reaction (PCR) (threshold for detection 300 copies/mL) and Alanine aminotransferase (ALT) normalization defined as ALT within normal limits on two successive visits for a patient with an elevated ALT (>1.0 x upper limit normal) at baseline summarized at Weeks 12 and 24.
Weeks 12 and 24

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in HBV DNA Concentration
Time Frame: Weeks 12 and 24
The change from baseline in HBV DNA concentration at Weeks 12 and 24 was analyzed using an analysis of covariance (ANCOVA) model with baseline HBV DNA concentration (log10 copies/ml) as a covariate, treatment and country as factors.
Weeks 12 and 24
Percentage of Participants Who Experienced Virologic Breakthrough at Weeks 48 and 52
Time Frame: Weeks 48 and 52
The percentage of participants with Virologic breakthrough at Week 48 and 52 by treatment. For the subgroup of patients on treatment who achieve HBV DNA >= 1 log10 copies/mL reduction from baseline on 2 consecutive visits, Virologic Breakthrough is defined as HBV DNA >= 1 log10 copies/mL from nadir on two consecutive visits.
Weeks 48 and 52
Percentage of Participants With Hepatitis B 'e' Antigen (HBeAg) Loss and HBeAg Seroconversion
Time Frame: Weeks 18, 24, 48, 52 and Treatment completion (TC)
HBeAg loss is defined as the loss of detectable serum HBeAg in a patient who was HBeAg positive at baseline. HBeAg seroconversion is defined as HBeAg loss with detectable Hepatitis B 'e' antibody (HBeAb). The efficacy was assessed for 18 weeks, 24 weeks, 48 weeks, 52 weeks and on treatment completion (TC).
Weeks 18, 24, 48, 52 and Treatment completion (TC)
Percentage of Participants Who Achieved HBV DNA Non-detectability With Telbivudine Monotherapy Versus Peginterferon Alpha-2a Monotherapy
Time Frame: Week 52
Antiviral efficacy was assessed by percentage of patients achieving HBV DNA non-detectability assay utilizing polymerase chain reaction (PCR) (threshold for detection 300 copies/mL); however, this analysis was not performed due to premature study termination.
Week 52
Percentage of Participants Who Achieved HBV DNA Non-detectability With Peginterferon Alpha-2a Plus Telbivudine Combination Therapy Versus Telbivudine Monotherapy
Time Frame: Week 52
Antiviral efficacy was assessed by percentage of patients achieving HBV DNA non-detectability assay utilizing polymerase chain reaction (PCR) (threshold for detection 300 copies/mL); however, this analysis was not performed due to premature study termination.
Week 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novartis

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2006

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2009

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2009

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 15, 2006

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 15, 2006

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 18, 2006

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 13, 2011

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 14, 2011

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CLDT600A2406

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings