Telbivudine in Adults Previously Treated in Idenix-Sponsored Telbivudine Studies

An Open Label Trial of Telbivudine (LdT) in Adults With Chronic Hepatitis B Previously Treated in Idenix-Sponsored Telbivudine Studies

This trial is being conducted as an open-label, extended-term study for patients with chronic hepatitis B who have previously completed an Idenix-sponsored trial with telbivudine.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: Telbivudine (LdT)

Detailed Description

Patients from 6 feeder trials could be eligible to enter current study CLDT600A2303 ( NCT00142298) if they met inclusion/exclusion criteria. The feeder studies were as follows:

• CLDT600A2302 (NV-02B-007)(NCT00057265), the GLOBE study, was a Phase III, randomized, doubleblind,multi-center, 104-week, pivotal study of telbivudine vs. lamivudine in treatment of naïve patients with compensated chronic hepatitis B. CLDT600A2302/NV-02B-007 (NCT00057265) is hereafter referred to as study 2302.
• NV-02B-015 (NCT00131742) was a Phase III, randomized, double-blind, 104-week study comparing the efficacy and safety of telbivudine (600 mg/day) to lamivudine (100 mg/day) in treatment of naïve Chinese patients with compensated chronic hepatitis B. NV-02B-015 (NCT00131742) is hereafter referred to as study 015.
• CLDT600A2301 (NV-02B-011)(NCT00076336) was a Phase III, randomized double-blind, multi-center, 104-week, pivotal study of telbivudine (600 mg/day) vs. lamivudine (100 mg/day) in treatment-naïve adults with decompensated chronic hepatitis B. CLDT600A2301/NV-02B-011 (NCT00076336) is hereafter referred to as study 2301.
• NV-02B-010 (NCT00124241) was a Phase IIb, 104-week extension study of telbivudine, lamivudine or the combination of both agents in patients with chronic hepatitis B who had completed the core study NV-02B-003 (NCT00124241). NV-02B-010 (NCT00124241) is hereafter referred to as study 010.

NV-02B-003 (NCT00124241) was a Phase IIa, 52-week study of telbivudine, lamivudine or the combination of both agents in patients with HBeAg-positive chronic hepatitis B.

• CLDT600A2401 (NV-02B-018) (NCT00115245) was a Phase IIIb, randomized, open-label, multi-center,52-week study of telbivudine vs. adefovir dipivoxil for 24 weeks then a switch to telbivudine for another 28 weeks in treatment-naïve patients with compensated chronic hepatitis B. CLDT600A2401/NV-02B-018 (NCT00115245) is hereafter referred to as study 2401.
• CLDT600A2402 (NV-02B-019) (NCT00132652) was a Phase IIIb, randomized, open-label, multi-center, 52-week study of switching lamivudine to telbivudine vs. continued on lamivudine treatment in adults with compensated chronic hepatitis B who were previously treated with lamivudine for 3-12 months. CLDT600A2402/NV-02-019 (NCT00132652) is hereafter referred to as study 2402.

PATIENT GROUPS:

GROUP A: Patients with HBeAg (+) or HBeAg (-) compensated chronic hepatitis B who did not discontinue treatment in their previous study due to an efficacy response and required further treatment or who had met the criteria for discontinuation of treatment in their previous study due to efficacy, but were being maintained on study drug by the principal investigator. For patients treated with telbivudine who enrolled into Group A from studies 2302 and 015, the total telbivudine treatment time (starting from feeder study baseline to the end of the on-treatment period in study 2303) was 208 weeks. For patients treated with lamivudine in studies 2302/015 and enrolled into group A and for all patients in group A from studies 2401/2402/010, the total telbivudine treatment time was 104 weeks.

GROUP B: Patients with HBeAg (+) or HBeAg (-) decompensated chronic hepatitis B who did not discontinue treatment in their previous study due to an efficacy response and required further treatment. Patients treated with telbivudine in study 2301 were enrolled to group B and the total telbivudine treatment time (starting from feeder study baseline to the end of the on-treatment period in study 2303) was 208 weeks. For patients treated with lamivudine in study 2301 and enrolled into group B, the total telbivudine treatment time was 104 weeks.

GROUP C: Patients with either compensated or decompensated chronic hepatitis B, who had discontinued study drug treatment in their previous Idenix-sponsored study due to an efficacy response as recommended by protocol. Patients who were eligible for treatment discontinuation in their previous study but who were, at the principal investigators discretion, continued on study therapy, were eligible to enter this study in Group C provided their treatment was discontinued at their last visit of the previous study. The feeder studies for group C of current study were study 2302/015, 2401, 2402, and 010. For patients who enrolled into group C, total telbivudine treatment time was 104 weeks starting from the baseline of the feeder studies to their last visit of the feeder studies. Patients were enrolled to current study (study 2303) for off-treatment follow-up after the treatment discontinuation due to efficacy. Hence, patients did not receive any study drug except in case of patients who relapsed and reinitiated treatment.

• Study Type: Interventional
• Enrollment (Actual): 1869
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Novartis Investigational Site
• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • Novartis Investigational Site
• China
  • Beijing
    • Beijing, Beijing, China
      • Novartis Investigational Site
• Czechia
  • Praha, Czechia
    • Novartis Investigational Site
• France
  • Paris, France, 75270
    • Novartis Investigational Site
• Germany
  • Hannover, Germany, 30159
    • Novartis Investigational Site
• Hong Kong
  • Hong Kong, Hong Kong, 999077
    • Novartis Investigational Site
• India
  • New Delhi, India
    • Novartis Investigational Site
• Israel
  • Nazareth, Israel, 1613101
    • Novartis Investigational Site
• Italy
  • Torino, Italy
    • Novartis Investigational Site
• Korea, Republic of
  • Seoul, Korea, Republic of
    • Novartis Investigational Site
• New Zealand
  • Hamilton, New Zealand
    • Novartis Investigational Site
• Poland
  • Krakow, Poland
    • Novartis Investigational Site
• Puerto Rico
  • Santurce, Puerto Rico
    • Novartis Investigational Site
• Singapore
  • Singapore, Singapore
    • Novartis Investigational Site
• Spain
  • Valencia, Spain
    • Novartis Investigational Site
• Taiwan
  • Tainan, Taiwan
    • Novartis Investigational Site
• Thailand
  • Bangkok, Thailand
    • Novartis Investigational Site
• Turkey
  • Istanbul, Turkey, TR-34353
    • Novartis Investigational Site
• United Kingdom
  • London, United Kingdom
    • Novartis Investigational Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85001
      • Novartis Investigational Site
  • California
    • Los Angeles, California, United States, 90001
      • Novartis Investigational Site
    • Los Angeles, California, United States, 90073
      • Novartis Investigational Site
    • Pasadena, California, United States, 91103
      • Novartis Investigational Site
    • Sacramento, California, United States
      • Novartis Investigational Site
    • San Diego, California, United States, 91945
      • Novartis Investigational Site
    • San Francisco, California, United States, 94115
      • Novartis Investigational Site
  • Florida
    • Sarasota, Florida, United States
      • Novartis Investigational Site
  • Georgia
    • Atlanta, Georgia, United States
      • Novartis Investigational Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96812
      • Novartis Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60176
      • Novartis Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Novartis Investigational Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • Novartis Investigational Site
  • Missouri
    • Saint Louis, Missouri, United States, 63143
      • Novartis Investigational Site
  • New York
    • New York, New York, United States, 10029
      • Novartis Investigational Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7211
      • Novartis Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19103
      • Novartis Investigational Site
  • Texas
    • Houston, Texas, United States, 77007
      • Novartis Investigational Site
  • Virginia
    • Richmond, Virginia, United States, 23220
      • Novartis Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 66 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient completed a previous qualifying Idenix-Sponsored trial with telbivudine
• Patient was not discontinued from previous Idenix-Sponsored study

Other protocol-defined inclusion criteria may apply

Exclusion Criteria:

• Patient is pregnant or breastfeeding
• Patient is co-infected with hepatitis C, hepatitis D or HIV

Other protocol-defined exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: telbivudine; telbivudine 600 mg p.o. daily for 104 weeks.

Drug: Telbivudine (LdT); Telbivudine was to be supplied as white to off-white, oval, bi-convex tablets for the 200 mg tablets and white to off-white ovaloid, slightly curved, beveled edges, film coated tablets for the 600 mg tablets. Study drug (600 mg) was to be self-administered by patients orally (p.o.) in a once daily regimen for 104 weeks; for study consistency, the daily dose had to be taken at the same time each day, with or without food.; Other Names: Sebivo®/Tyzeka®; LdT600

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Maintained Therapeutic Response [Group A: LdT Pool 2302/015]	The maintained therapeutic response is defined as hepatitis B virus (HBV) DNA < 5 log10 copies/mL and either hepatitis Be antigen (HBeAg) loss or alanine aminotransferase (ALT) normalized. HBeAg loss is loss of detectable serum HBeAg in a patient who was HBeAg-positive at feeder baseline. ALT normalized is defined as ALT within normal limits for a patient with an elevated ALT level (>1.0 × ULN) at either the feeder baseline or feeder screening visit. All efficacy data were analyzed separately for HBeAg-positive and HBeAg-negative patients.	156 weeks, 208 weeks (from feeder study baseline)
Percentage of Participants Who Maintained Therapeutic Response [Group A: LAM Pool 2302/015]	The maintained therapeutic response is defined as hepatitis B virus (HBV) DNA < 5 log10 copies/mL and either hepatitis Be antigen (HBeAg) loss or alanine aminotransferase (ALT) normalized. HBeAg loss is loss of detectable serum HBeAg in a patient who was HBeAg-positive at feeder baseline. ALT normalized is defined as ALT within normal limits for a patient with an elevated ALT level (>1.0 × ULN) at either the feeder baseline or feeder screening visit. All efficacy data were analyzed separately for HBeAg-positive and HBeAg-negative patients.	52 weeks, 104 weeks
Percentage of Participants Who Maintained Therapeutic Response [Group A: Feeder Studies 2401/2402/010]	The maintained therapeutic response is defined as hepatitis B virus (HBV) DNA < 5 log10 copies/mL and either hepatitis Be antigen (HBeAg) loss or alanine aminotransferase (ALT) normalized. HBeAg loss is loss of detectable serum HBeAg in a patient who was HBeAg-positive at feeder baseline. ALT normalized is defined as ALT within normal limits for a patient with an elevated ALT level (>1.0 × ULN) at either the feeder baseline or feeder screening visit. All efficacy data were analyzed separately for HBeAg-positive and HBeAg-negative patients.	52 weeks, 104 weeks
Percentage of Participants With Maintained Clinical Response [Group B: LdT 2301]	Maintained clinical response is defined as achievement of serum HBV DNA < 4 log10 copies/mL, normal serum ALT level and improvement or stabilization in Child-Turcotte-Pugh (CTP) score. Total CTP score ranges from 5 to 15; higher scores indicate liver impairment. Improvement is defined as a 2-point or greater reduction in CTP score, and stabilization is defined as a less than 2-point change in CTP score, compared to the patient's baseline value. Analysis was done on the overall per protocol (PP) population and separately for the HBeAg-positive and HBeAg-negative subpopulation.	156 weeks, 208 weeks (from feeder study baseline)
Percentage of Participants With Maintained Clinical Response [Group B: LAM 2301]	Maintained clinical response is defined as achievement of serum HBV DNA < 4 log10 copies/mL, normal serum ALT level and improvement or stabilization in Child-Turcotte-Pugh (CTP) score. Total CTP score ranges from 5 to 15; higher scores indicate liver impairment. Improvement is defined as a 2-point or greater reduction in CTP score, and stabilization is defined as a less than 2-point change in CTP score, compared to the patient's baseline value. Analysis was done on the overall per protocol (PP) population and separately for the HBeAg-positive and HBeAg-negative subpopulation.	52 weeks,104 weeks
Percentage of Participants With Sustained Therapeutic Response [Group C: LdT Pool and LAM Pool (2302/015)]	The primary efficacy endpoint for Group C patients was the percentage of patients with sustained therapeutic response (defined as HBV DNA < 5 log10 copies/mL and either HBeAg loss or ALT normalized) at Weeks 52 and 104 of off-treatment follow-up. HBeAg loss is loss of detectable serum HBeAg in a patient who was HBeAg-positive at feeder baseline. ALT normalized is ALT within normal limits for a patient with an elevated ALT level (>1.0 × ULN) at either the feeder baseline or feeder screening visit. All efficacy data were analyzed separately for HBeAg-positive and HBeAg-negative patients.	52 weeks,104 weeks
Percentage of Participants With Sustained Therapeutic Response [Group C: Other Feeder Studies]	The primary efficacy endpoint for Group C (other feeder studies) was the percentage of patients with sustained therapeutic response (defined as HBV DNA < 5 log10 copies/mL and either HBeAg loss or ALT normalized) at Weeks 52 and 104 of off-treatment follow-up. Patients were enrolled for off-treatment follow-up after the treatment discontinuation due to efficacy at their last visit of the feeder studies. Hence, patients did not receive study drug except in case of patients who relapsed and reinitiated treatment. No statistical summary was performed , only patient listing was generated.	52 weeks,104 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
To Longitudinally Assess the Longer-term Antiviral Efficacy Achieved With Telbivudine Treatment	52 weeks, 104 weeks, 156 weeks, 208 weeks
To Longitudinally Assess the Clinical Efficacy of Longer-term Treatment With Telbivudine	52 weeks, 104 weeks, 156 weeks, 208 weeks
To Longitudinally Assess the Durability of HBeAg Responses Achieved With Telbivudine Treatment and Other Previous Treatments in Patients	52 weeks, 104 weeks, 156 weeks, 208 weeks
To Determine the Longitudinal Frequency of Virologic Breakthrough and Characterize the Associated Mutations in the HBV Polymerase Gene in HBV DNA Amplified From Sera of Patients With Virologic Breakthrough	52 weeks, 104 weeks, 156 weeks, 208 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Collaborators: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Hsu CW, Chao YC, Lee CM, Chang TT, Chen YC. Efficacy of telbivudine in Taiwanese chronic hepatitis B patients compared with GLOBE extension study and predicting treatment outcome by HBV DNA kinetics at week 24. BMC Gastroenterol. 2012 Dec 13;12:178. doi: 10.1186/1471-230X-12-178.

Study record dates

Study Major Dates

• Study Start: March 1, 2005
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: August 31, 2005
• First Submitted That Met QC Criteria: August 31, 2005
• First Posted (Estimate): September 2, 2005

Study Record Updates

• Last Update Posted (Actual): August 21, 2020
• Last Update Submitted That Met QC Criteria: August 9, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis B; Hepatitis; Hepatitis B, Chronic; Hepatitis, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Telbivudine
• Other Study ID Numbers: CLDT600A2303; NV-02B-022 (Other Identifier: Idenix)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

IPD Plan Description

Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com