Telbivudine in Adults Previously Treated in Idenix-Sponsored Telbivudine Studies

Chronic Hepatitis B Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00142298
• Other study ID #: CLDT600A2303
• Secondary ID: NV-02B-022
• Status: Completed
• Phase: Phase 3
• Start date: March 2005
• Est. completion date: November 2009

Study information

• Verified date: August 2020
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1869
• Est. completion date: November 2009
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

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.

Locations

Country	Name	City	State
Australia	Novartis Investigational Site	Heidelberg	Victoria
Canada	Novartis Investigational Site	Toronto	Ontario
China	Novartis Investigational Site	Beijing	Beijing
Czechia	Novartis Investigational Site	Praha
France	Novartis Investigational Site	Paris
Germany	Novartis Investigational Site	Hannover
Hong Kong	Novartis Investigational Site	Hong Kong
India	Novartis Investigational Site	New Delhi
Israel	Novartis Investigational Site	Nazareth
Italy	Novartis Investigational Site	Torino
Korea, Republic of	Novartis Investigational Site	Seoul
New Zealand	Novartis Investigational Site	Hamilton
Poland	Novartis Investigational Site	Krakow
Puerto Rico	Novartis Investigational Site	Santurce
Singapore	Novartis Investigational Site	Singapore
Spain	Novartis Investigational Site	Valencia
Taiwan	Novartis Investigational Site	Tainan
Thailand	Novartis Investigational Site	Bangkok
Turkey	Novartis Investigational Site	Istanbul
United Kingdom	Novartis Investigational Site	London
United States	Novartis Investigational Site	Ann Arbor	Michigan
United States	Novartis Investigational Site	Atlanta	Georgia
United States	Novartis Investigational Site	Boston	Massachusetts
United States	Novartis Investigational Site	Chapel Hill	North Carolina
United States	Novartis Investigational Site	Chicago	Illinois
United States	Novartis Investigational Site	Honolulu	Hawaii
United States	Novartis Investigational Site	Houston	Texas
United States	Novartis Investigational Site	Los Angeles	California
United States	Novartis Investigational Site	Los Angeles	California
United States	Novartis Investigational Site	New York	New York
United States	Novartis Investigational Site	Pasadena	California
United States	Novartis Investigational Site	Philadelphia	Pennsylvania
United States	Novartis Investigational Site	Phoenix	Arizona
United States	Novartis Investigational Site	Richmond	Virginia
United States	Novartis Investigational Site	Sacramento	California
United States	Novartis Investigational Site	Saint Louis	Missouri
United States	Novartis Investigational Site	San Diego	California
United States	Novartis Investigational Site	San Francisco	California
United States	Novartis Investigational Site	Sarasota	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals	Merck Sharp & Dohme Corp.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  China,  Czechia,  France,  Germany,  Hong Kong,  India,  Israel,  Italy,  Korea, Republic of,  New Zealand,  Poland,  Puerto Rico,  Singapore,  Spain,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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
Primary	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
Primary	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)
Primary	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
Primary	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
Primary	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	To Longitudinally Assess the Longer-term Antiviral Efficacy Achieved With Telbivudine Treatment		52 weeks, 104 weeks, 156 weeks, 208 weeks
Secondary	To Longitudinally Assess the Clinical Efficacy of Longer-term Treatment With Telbivudine		52 weeks, 104 weeks, 156 weeks, 208 weeks
Secondary	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
Secondary	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