Chronic Hepatitis B
Conditions
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.
Interventions
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.
Sponsors
Merck Sharp & Dohme LLC
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Therapeutic Response [Group C: Other Feeder Studies] | 52 weeks,104 weeks | 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. |
| Percentage of Participants Who Maintained Therapeutic Response [Group A: Feeder Studies 2401/2402/010] | 52 weeks, 104 weeks | 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. |
| Percentage of Participants With Maintained Clinical Response [Group B: LdT 2301] | 156 weeks, 208 weeks (from feeder study baseline) | 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. |
| Percentage of Participants With Maintained Clinical Response [Group B: LAM 2301] | 52 weeks,104 weeks | 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. |
| Percentage of Participants With Sustained Therapeutic Response [Group C: LdT Pool and LAM Pool (2302/015)] | 52 weeks,104 weeks | 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. |
| Percentage of Participants Who Maintained Therapeutic Response [Group A: LdT Pool 2302/015] | 156 weeks, 208 weeks (from feeder study baseline) | 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. |
| Percentage of Participants Who Maintained Therapeutic Response [Group A: LAM Pool 2302/015] | 52 weeks, 104 weeks | 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. |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| To Longitudinally Assess the Longer-term Antiviral Efficacy Achieved With Telbivudine Treatment | 52 weeks, 104 weeks, 156 weeks, 208 weeks |
Countries
Australia, Canada, China, Czechia, France, Germany, Hong Kong, India, Israel, Italy, New Zealand, Poland, Puerto Rico, Singapore, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
An open-label trial of telbivudine in adults with chronic hepatitis B previously treated in Idenix-sponsored telbivudine studies. Study start March 2005 and completed November 2009.
Participants by arm
| Arm | Count |
|---|---|
| Group A : LdT Pool 2302/015 Subjects with HBeAg (+) or HBeAg (-) compensated chronic hepatitis B from phase III pivotal, registration studies Subjects with HBeAg (+) or HBeAg (-) compensated chronic hepatitis B from phase III pivotal, registration studies 2302 (NCT00057265) and 015 (NCT00131742) treated with Telbivudine. Telbivudine 600 mg by mouth (p.o.) daily for 104 weeks. The total telbivudine treatment time starting from feeder study baseline to the end of the on-treatment period in study 2303 was 208 weeks. | 667 |
| Group A : LAM Pool 2302/015 Subjects with HBeAg (+) or HBeAg (-) compensated chronic hepatitis B from phase III pivotal, registration studies 2302 (NCT00057265) and 015 (NCT00131742) treated with Lamivudine. Telbivudine 600 mg by mouth (p.o.) daily for 104 weeks. | 632 |
| Group A: Feeder Study 2401 Subjects with HBeAg (+) or HBeAg (-) compensated chronic hepatitis B from phase IIIb, registration study CLDT600A2401 (NCT00115245) treated with Telbivudine. Telbivudine 600 mg by mouth (p.o.) daily for 104 weeks. | 123 |
| Group A: Feeder Study 2402 Subjects with HBeAg (+) or HBeAg (-) compensated chronic hepatitis B from phase IIIb, registration study CLDT600A2402 (NCT00132652) and treated with Lamivudine or Telbivudine. Telbivudine 600 mg by mouth (p.o.) daily for 104 weeks. | 206 |
| Group A: Feeder Study 010 Subjects with HBeAg (+) or HBeAg (-) compensated chronic hepatitis B were from phase IIb study NV-02B-010 (NCT00124241) of telbivudine, lamivudine or the combination of both agents. Telbivudine 600 mg by mouth (p.o.) daily for 104 weeks. | 56 |
| Group B: LdT 2301 Subjects with HBeAg (+) or HBeAg (-) decompensated chronic hepatitis B from phase III pivotal, registration study 2301 (NCT00076336) treated with Telbivudine. Telbivudine 600 mg by mouth (p.o.) daily for 104 weeks. The total telbivudine treatment time starting from feeder study baseline to the end of the on-treatment period in study 2303 was 208 weeks. | 26 |
| Group B: LAM 2301 Subjects with HBeAg (+) or HBeAg (-) decompensated chronic hepatitis B from phase III pivotal, registration studies 2301 (NCT00076336) treated with Lamivudine. Telbivudine 600 mg by mouth (p.o.) daily for 104 weeks. | 23 |
| Group C: LdT Pool 2302/015 Subjects with either compensated or decompensated chronic hepatitis B from phase III pivotal, registration studies 2302 (NCT00057265) and 015 (NCT00131742) treated with Telbivudine. 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 any study drug except in case of patients who relapsed and reinitiated treatment. | 66 |
| Group C: LAM Pool 2302/015 Subjects with either compensated or decompensated chronic hepatitis B from phase III pivotal, registration studies 2302 (NCT00057265) and 015 (NCT00131742) treated with Lamivudine. 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 any study drug except in case of patients who relapsed and reinitiated treatment. | 57 |
| Group C: Other Feeder Studies Patients with either compensated or decompensated chronic hepatitis B, from 2401 (NCT00115245), 2402 (NCT00132652) and 010 (NCT00124241). 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 any study drug except in case of patients who relapsed and reinitiated treatment. | 13 |
| Total | 1,869 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 10 | 10 | 1 | 5 | 2 | 2 | 0 | 0 | 0 | 0 |
| Overall Study | Clinical disease progression | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Death | 1 | 1 | 1 | 0 | 0 | 6 | 0 | 0 | 0 | 0 |
| Overall Study | Lack of Efficacy | 44 | 62 | 9 | 12 | 1 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 |
| Overall Study | Non-compliance | 15 | 13 | 0 | 6 | 1 | 0 | 0 | 3 | 3 | 0 |
| Overall Study | Other- not specified | 0 | 3 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Patient, Investigator,or Sponsor request | 66 | 60 | 11 | 51 | 4 | 3 | 1 | 4 | 1 | 0 |
| Overall Study | Pregnancy | 4 | 4 | 2 | 3 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Treatment Failure | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 0 | 0 | 0 |
| Overall Study | Virologic breakthrough | 19 | 23 | 9 | 7 | 2 | 3 | 3 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Group A : LdT Pool 2302/015 | Group A : LAM Pool 2302/015 | Group A: Feeder Study 2401 | Group A: Feeder Study 2402 | Group A: Feeder Study 010 | Group B: LdT 2301 | Group B: LAM 2301 | Group C: LdT Pool 2302/015 | Group C: LAM Pool 2302/015 | Group C: Other Feeder Studies |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 30-50 years | 948 Participants | 320 Participants | 325 Participants | 66 Participants | 122 Participants | 40 Participants | 10 Participants | 5 Participants | 31 Participants | 24 Participants | 5 Participants |
| Age, Customized < 30 years | 663 Participants | 276 Participants | 207 Participants | 51 Participants | 54 Participants | 9 Participants | 1 Participants | 0 Participants | 30 Participants | 27 Participants | 8 Participants |
| Age, Customized > 50 years | 258 Participants | 71 Participants | 100 Participants | 6 Participants | 30 Participants | 7 Participants | 15 Participants | 18 Participants | 5 Participants | 6 Participants | 0 Participants |
| Sex: Female, Male Female | 433 Participants | 147 Participants | 142 Participants | 30 Participants | 53 Participants | 9 Participants | 9 Participants | 6 Participants | 20 Participants | 14 Participants | 3 Participants |
| Sex: Female, Male Male | 1436 Participants | 520 Participants | 490 Participants | 93 Participants | 153 Participants | 47 Participants | 17 Participants | 17 Participants | 46 Participants | 43 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 318 / 655 | 309 / 626 | 24 / 50 | 74 / 122 | 88 / 206 | 21 / 26 | 19 / 23 | 40 / 66 | 33 / 57 | 13 / 13 |
| serious Total, serious adverse events | 45 / 655 | 21 / 626 | 3 / 50 | 10 / 122 | 14 / 206 | 16 / 26 | 10 / 23 | 1 / 66 | 2 / 57 | 2 / 13 |
Outcome results
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.
Time frame: 52 weeks, 104 weeks
Population: Per protocol (PP) population. The PP analysis was done on the PP population, separately for the HBeAg-positive and HBeAg-negative subpopulation (status as feeder baseline). n = the number of HBeAg-positive/HBeAg-negative patients who were eligible for maintained therapeutic response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group A : LdT Pool 2302/015 | Percentage of Participants Who Maintained Therapeutic Response [Group A: Feeder Studies 2401/2402/010] | HBeAg Positive: 52 week (n = 103, 79, 43) | 77.7 Percentage of Participants |
| Group A : LdT Pool 2302/015 | Percentage of Participants Who Maintained Therapeutic Response [Group A: Feeder Studies 2401/2402/010] | HBeAg Positive: 104 week (n = 66, 15, 30) | 81.8 Percentage of Participants |
| Group A : LdT Pool 2302/015 | Percentage of Participants Who Maintained Therapeutic Response [Group A: Feeder Studies 2401/2402/010] | HBeAg Negative: 52 week (n = 0, 37, 0) | NA Percentage of Participants |
| Group A : LdT Pool 2302/015 | Percentage of Participants Who Maintained Therapeutic Response [Group A: Feeder Studies 2401/2402/010] | HBeAg Negative: 104 week (n = 0, 10, 0) | NA Percentage of Participants |
| Group A: Feeder Study 2402 | Percentage of Participants Who Maintained Therapeutic Response [Group A: Feeder Studies 2401/2402/010] | HBeAg Negative: 104 week (n = 0, 10, 0) | 60.0 Percentage of Participants |
| Group A: Feeder Study 2402 | Percentage of Participants Who Maintained Therapeutic Response [Group A: Feeder Studies 2401/2402/010] | HBeAg Positive: 52 week (n = 103, 79, 43) | 35.4 Percentage of Participants |
| Group A: Feeder Study 2402 | Percentage of Participants Who Maintained Therapeutic Response [Group A: Feeder Studies 2401/2402/010] | HBeAg Negative: 52 week (n = 0, 37, 0) | 54.1 Percentage of Participants |
| Group A: Feeder Study 2402 | Percentage of Participants Who Maintained Therapeutic Response [Group A: Feeder Studies 2401/2402/010] | HBeAg Positive: 104 week (n = 66, 15, 30) | 46.7 Percentage of Participants |
| Group A: Feeder Study 010 | Percentage of Participants Who Maintained Therapeutic Response [Group A: Feeder Studies 2401/2402/010] | HBeAg Negative: 104 week (n = 0, 10, 0) | NA Percentage of Participants |
| Group A: Feeder Study 010 | Percentage of Participants Who Maintained Therapeutic Response [Group A: Feeder Studies 2401/2402/010] | HBeAg Positive: 104 week (n = 66, 15, 30) | 76.7 Percentage of Participants |
| Group A: Feeder Study 010 | Percentage of Participants Who Maintained Therapeutic Response [Group A: Feeder Studies 2401/2402/010] | HBeAg Negative: 52 week (n = 0, 37, 0) | NA Percentage of Participants |
| Group A: Feeder Study 010 | Percentage of Participants Who Maintained Therapeutic Response [Group A: Feeder Studies 2401/2402/010] | HBeAg Positive: 52 week (n = 103, 79, 43) | 69.8 Percentage of Participants |
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.
Time frame: 52 weeks, 104 weeks
Population: Per protocol (PP) population. The PP analysis was done separately for the HBeAg-positive and HBeAg-negative subpopulation (status at feeder baseline). n = the number of HBeAg-positive/HBeAg-negative patients who were eligible for maintained therapeutic response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group A : LdT Pool 2302/015 | Percentage of Participants Who Maintained Therapeutic Response [Group A: LAM Pool 2302/015] | HBeAg Positive: week 52 (n=338) | 60.1 Percentage of Participants |
| Group A : LdT Pool 2302/015 | Percentage of Participants Who Maintained Therapeutic Response [Group A: LAM Pool 2302/015] | HBeAg Positive: week 104 (n=101) | 65.3 Percentage of Participants |
| Group A : LdT Pool 2302/015 | Percentage of Participants Who Maintained Therapeutic Response [Group A: LAM Pool 2302/015] | HBeAg Negative: week 52 (n=182) | 80.8 Percentage of Participants |
| Group A : LdT Pool 2302/015 | Percentage of Participants Who Maintained Therapeutic Response [Group A: LAM Pool 2302/015] | HBeAg Negative: week 104 (n=79) | 81.0 Percentage of Participants |
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.
Time frame: 156 weeks, 208 weeks (from feeder study baseline)
Population: Per protocol (PP) population. The PP analysis was done on separately for the HBeAg-positive and HBeAg-negative subpopulation (status at feeder baseline). n = the number of HBeAg-positive/HBeAg-negative patients who were eligible for maintained therapeutic response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group A : LdT Pool 2302/015 | Percentage of Participants Who Maintained Therapeutic Response [Group A: LdT Pool 2302/015] | HBeAg Positive: week 156 (n=338) | 67.2 Percentage of participants |
| Group A : LdT Pool 2302/015 | Percentage of Participants Who Maintained Therapeutic Response [Group A: LdT Pool 2302/015] | HBeAg Positive: week 208 (n=252) | 73.8 Percentage of participants |
| Group A : LdT Pool 2302/015 | Percentage of Participants Who Maintained Therapeutic Response [Group A: LdT Pool 2302/015] | HBeAg Negative: week 156 (n=197) | 81.7 Percentage of participants |
| Group A : LdT Pool 2302/015 | Percentage of Participants Who Maintained Therapeutic Response [Group A: LdT Pool 2302/015] | HBeAg Negative: week 208 (n=168) | 86.3 Percentage of participants |
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.
Time frame: 52 weeks,104 weeks
Population: Per protocol (PP) population. The PP analysis was done on the overall PP population and separately for the HBeAg-positive and HBeAg-negative subpopulation (status at feeder baseline). n = the number of patients who were eligible for maintained clinical response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group A : LdT Pool 2302/015 | Percentage of Participants With Maintained Clinical Response [Group B: LAM 2301] | HBeAg Positive: week 52 (n=4) | 100 Percentage of Participants |
| Group A : LdT Pool 2302/015 | Percentage of Participants With Maintained Clinical Response [Group B: LAM 2301] | HBeAg Positive: week 104 (n=1) | 100 Percentage of Participants |
| Group A : LdT Pool 2302/015 | Percentage of Participants With Maintained Clinical Response [Group B: LAM 2301] | HBeAg Negative: week 52 (n=11) | 72.7 Percentage of Participants |
| Group A : LdT Pool 2302/015 | Percentage of Participants With Maintained Clinical Response [Group B: LAM 2301] | HBeAg Negative: week 104 (n=5) | 100 Percentage of Participants |
| Group A : LdT Pool 2302/015 | Percentage of Participants With Maintained Clinical Response [Group B: LAM 2301] | Overall: week 52 (n= 15) | 80.0 Percentage of Participants |
| Group A : LdT Pool 2302/015 | Percentage of Participants With Maintained Clinical Response [Group B: LAM 2301] | Overall: week 104 (n= 6) | 100 Percentage of Participants |
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.
Time frame: 156 weeks, 208 weeks (from feeder study baseline)
Population: Per protocol (PP) population. The PP analysis was done on the overall PP population and separately for the HBeAg-positive and HBeAg-negative subpopulation (status at feeder baseline). n = the number of patients who were eligible for maintained clinical response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group A : LdT Pool 2302/015 | Percentage of Participants With Maintained Clinical Response [Group B: LdT 2301] | HBeAg Positive: week 156 (n= 4) | 100 Percentage of Participants |
| Group A : LdT Pool 2302/015 | Percentage of Participants With Maintained Clinical Response [Group B: LdT 2301] | HBeAg Positive: week 208 (n= 1) | 100 Percentage of Participants |
| Group A : LdT Pool 2302/015 | Percentage of Participants With Maintained Clinical Response [Group B: LdT 2301] | HBeAg Negative: week 156 (n= 11) | 72.7 Percentage of Participants |
| Group A : LdT Pool 2302/015 | Percentage of Participants With Maintained Clinical Response [Group B: LdT 2301] | HBeAg Negative: week 208 (n= 7) | 71.4 Percentage of Participants |
| Group A : LdT Pool 2302/015 | Percentage of Participants With Maintained Clinical Response [Group B: LdT 2301] | Overall: Week 156 (n= 15) | 80.0 Percentage of Participants |
| Group A : LdT Pool 2302/015 | Percentage of Participants With Maintained Clinical Response [Group B: LdT 2301] | Overall: Week 208 (n= 8) | 75.0 Percentage of Participants |
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.
Time frame: 52 weeks,104 weeks
Population: The per protocol population. n= is the number of HBeAg-positive/HBeAg-negative patients from per protocol population who achieved maintained response at the end of treatment and had off-treatment assessment to determine the sustained response at that time point or lost sustained response before the off-treatment timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group A : LdT Pool 2302/015 | Percentage of Participants With Sustained Therapeutic Response [Group C: LdT Pool and LAM Pool (2302/015)] | HBeAg Positive: week 52 (n= 53, 42) | 69.8 Percentage of Participants |
| Group A : LdT Pool 2302/015 | Percentage of Participants With Sustained Therapeutic Response [Group C: LdT Pool and LAM Pool (2302/015)] | HBeAg Positive: week 104 (n= 42, 32) | 57.1 Percentage of Participants |
| Group A : LdT Pool 2302/015 | Percentage of Participants With Sustained Therapeutic Response [Group C: LdT Pool and LAM Pool (2302/015)] | HBeAg Negative: week 52 (n= 3, 5) | 0.0 Percentage of Participants |
| Group A : LdT Pool 2302/015 | Percentage of Participants With Sustained Therapeutic Response [Group C: LdT Pool and LAM Pool (2302/015)] | HBeAg Negative: week 104 (n= 3, 6) | 0.0 Percentage of Participants |
| Group A: Feeder Study 2402 | Percentage of Participants With Sustained Therapeutic Response [Group C: LdT Pool and LAM Pool (2302/015)] | HBeAg Negative: week 104 (n= 3, 6) | 83.3 Percentage of Participants |
| Group A: Feeder Study 2402 | Percentage of Participants With Sustained Therapeutic Response [Group C: LdT Pool and LAM Pool (2302/015)] | HBeAg Positive: week 52 (n= 53, 42) | 73.8 Percentage of Participants |
| Group A: Feeder Study 2402 | Percentage of Participants With Sustained Therapeutic Response [Group C: LdT Pool and LAM Pool (2302/015)] | HBeAg Negative: week 52 (n= 3, 5) | 80.0 Percentage of Participants |
| Group A: Feeder Study 2402 | Percentage of Participants With Sustained Therapeutic Response [Group C: LdT Pool and LAM Pool (2302/015)] | HBeAg Positive: week 104 (n= 42, 32) | 62.5 Percentage of Participants |
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.
Time frame: 52 weeks,104 weeks
Population: In Group C: other feeder study reporting group, there were only 13 patients; hence, no summary statistics were performed. Only listings were generated.
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
Time frame: 52 weeks, 104 weeks, 156 weeks, 208 weeks
Secondary
To Longitudinally Assess the Clinical Efficacy of Longer-term Treatment With Telbivudine
Time frame: 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
Time frame: 52 weeks, 104 weeks, 156 weeks, 208 weeks
Secondary
To Longitudinally Assess the Longer-term Antiviral Efficacy Achieved With Telbivudine Treatment
Time frame: 52 weeks, 104 weeks, 156 weeks, 208 weeks