Clinical trial NCT00142298: Telbivudine in Adults Previously Treated in Idenix-Sponsored Telbivudine Studies
Official title: An Open Label Trial of Telbivudine (LdT) in Adults With Chronic Hepatitis B Previously Treated in Idenix-Sponsored Telbivudine Studies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Hepatitis B
Lead sponsor: Novartis
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2005-09-02
Enrollment: 1869
Sex: ALL
Minimum age (years): 16
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants Who Maintained Therapeutic Response [Group A: LdT Pool 2302/015]
timeFrame: 156 weeks, 208 weeks (from feeder study baseline)
measure: Percentage of Participants Who Maintained Therapeutic Response [Group A: LAM Pool 2302/015]
timeFrame: 52 weeks, 104 weeks
measure: Percentage of Participants Who Maintained Therapeutic Response [Group A: Feeder Studies 2401/2402/010]
timeFrame: 52 weeks, 104 weeks
measure: Percentage of Participants With Maintained Clinical Response [Group B: LdT 2301]
timeFrame: 156 weeks, 208 weeks (from feeder study baseline)
measure: Percentage of Participants With Maintained Clinical Response [Group B: LAM 2301]
timeFrame: 52 weeks,104 weeks
measure: Percentage of Participants With Sustained Therapeutic Response [Group C: LdT Pool and LAM Pool (2302/015)]
timeFrame: 52 weeks,104 weeks
measure: Percentage of Participants With Sustained Therapeutic Response [Group C: Other Feeder Studies]
timeFrame: 52 weeks,104 weeks
Secondary outcomes:
measure: To Longitudinally Assess the Longer-term Antiviral Efficacy Achieved With Telbivudine Treatment
timeFrame: 52 weeks, 104 weeks, 156 weeks, 208 weeks
measure: To Longitudinally Assess the Clinical Efficacy of Longer-term Treatment With Telbivudine
timeFrame: 52 weeks, 104 weeks, 156 weeks, 208 weeks
measure: To Longitudinally Assess the Durability of HBeAg Responses Achieved With Telbivudine Treatment and Other Previous Treatments in Patients
timeFrame: 52 weeks, 104 weeks, 156 weeks, 208 weeks
measure: 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
timeFrame: 52 weeks, 104 weeks, 156 weeks, 208 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Novartis Investigational Site
state: Arizona
city: Los Angeles
country: United States
facility: Novartis Investigational Site
state: California
city: Los Angeles
country: United States
facility: Novartis Investigational Site
state: California
city: Pasadena
country: United States
facility: Novartis Investigational Site
state: California
city: Sacramento
country: United States
facility: Novartis Investigational Site
state: California
city: San Diego
country: United States
facility: Novartis Investigational Site
state: California
city: San Francisco
country: United States
facility: Novartis Investigational Site
state: California
city: Sarasota
country: United States
facility: Novartis Investigational Site
state: Florida
city: Atlanta
country: United States
facility: Novartis Investigational Site
state: Georgia
city: Honolulu
country: United States
facility: Novartis Investigational Site
state: Hawaii
city: Chicago
country: United States
facility: Novartis Investigational Site
state: Illinois
city: Boston
country: United States
facility: Novartis Investigational Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Novartis Investigational Site
state: Michigan
city: Saint Louis
country: United States
facility: Novartis Investigational Site
state: Missouri
city: New York
country: United States
facility: Novartis Investigational Site
state: New York
city: Chapel Hill
country: United States
facility: Novartis Investigational Site
state: North Carolina
city: Philadelphia
country: United States
facility: Novartis Investigational Site
state: Pennsylvania
city: Houston
country: United States
facility: Novartis Investigational Site
state: Texas
city: Richmond
country: United States
facility: Novartis Investigational Site
state: Virginia
city: Heidelberg
country: Australia
facility: Novartis Investigational Site
state: Victoria
city: Toronto
country: Canada
facility: Novartis Investigational Site
state: Ontario
city: Beijing
country: China
facility: Novartis Investigational Site
state: Beijing
city: Praha
country: Czechia
facility: Novartis Investigational Site
city: Paris
country: France
facility: Novartis Investigational Site
city: Hannover
country: Germany
facility: Novartis Investigational Site
city: Hong Kong
country: Hong Kong
facility: Novartis Investigational Site
city: New Delhi
country: India
facility: Novartis Investigational Site
city: Nazareth
country: Israel
facility: Novartis Investigational Site
city: Torino
country: Italy
facility: Novartis Investigational Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigational Site
city: Hamilton
country: New Zealand
facility: Novartis Investigational Site
city: Krakow
country: Poland
facility: Novartis Investigational Site
city: Santurce
country: Puerto Rico
facility: Novartis Investigational Site
city: Singapore
country: Singapore
facility: Novartis Investigational Site
city: Valencia
country: Spain
facility: Novartis Investigational Site
city: Tainan
country: Taiwan
facility: Novartis Investigational Site
city: Bangkok
country: Thailand
facility: Novartis Investigational Site
city: Istanbul
country: Turkey
facility: Novartis Investigational Site
city: London
country: United Kingdom
facility: Novartis Investigational Site
Study officials:
References:
citation: 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.