Chronic Hepatitis B
Conditions
Keywords
Chronic hepatitis B, pediatrics, antiviral treatment, telbivudine
Brief summary
The purpose of the study was to assess the efficacy and safety of telbivudine at a dose of 20 mg/kg up to a maximum of 600 mg q.d. in compensated pediatric HBeAg-positive and negative CHB patients aged 2 to \<18 years with the indication of antiviral CHB treatment. This study was part of the commitments of the pediatric development plan for telbivudine in Europe and US.
Interventions
DRUGTelbivudine
Patients of any age and weight\< 30kg: telbivudine oral solution (20 mg/mL): 20 mg/kg up to 600 mg q.d corresponding to weight (kg) x1mL, p.o. once daily Patients \< 12 years old and weight≥ 30kg: telbivudine oral solution (20mg/mL), 600 mg/day corresponding to 30 mL p.o. once daily Patients ≥ 12 years old and weight ≥ 30kg: telbivudine film-coated tablet, 600 mg/day, corresponding to 1 tablet p.o. once daily
DRUGPlacebo
Patients of any age and weight \< 30kg: placebo oral solution corresponding to weight (kg) x1mL, p.o. once daily Patients \< 12 years old and weight ≥ 30kg: placebo oral solution corresponding to 30 mL p.o. once daily Patients ≥ 12 years old and weight ≥ 30kg: placebo tablet, corresponding to 1 tablet p.o. once daily
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Clinical history compatible with compensated chronic hepatitis B * Documented compensated chronic hepatitis B defined by the following: 1. Positive serum HBsAg at screening and at least one other documentation of HBsAg positive at least 6 months prior to screening 2. For HBeAg positive patients at screening, significant biologic and/or histologic signs of disease activity following EASL guidelines recommendations for CHB pediatric patients (serum HBV DNA level ≥ 5 log10 copies/mL (or 20 000 IU/mL) (COBAS Taqman®) at screening ; serum ALT ≥ 1.5×ULN and \< 10×ULN (pediatric ULN) for two times during the screening period or within 6 months prior to screening 3. For HBeAg negative patients at screening, significant biologic and/or histologic signs of disease activity following EASL guidelines recommendations for CHB pediatric patients (serum HBV DNA level ≥ 4 log10 copies/mL (or 2 000 IU/mL) (COBAS Taqman®) at screening) ; serum ALT ≥ 1.0 ×ULN and \< 10×ULN (pediatric ULN) for two times during the screening period or within 12 months prior to screening) Key
Exclusion criteria
* Patients with acute or chronic infection of HCV, HDV, HIV, or with acute infection of HAV, HEV, CMV, EBV, or HSV. * Patient has received treatment of interferon or any other immunomodulatory agents within the last 12 months prior to screening or any nucleoside or nucleotide drugs or other anti-CHB treatment (approved or investigational) at any time before screening * Patient has a medical condition that requires frequent use of systemic acyclovir or famciclovir, systemic corticosteroids, potentially hepatotoxic drugs or nephrotoxic drugs or chemotherapy * Patient has one or more additional known primary or secondary causes of liver disease, other than CHB; has a decompensated liver disease ; is a Liver transplant recipient or organ or bone marrow transplant recipient. * History of any other acute or chronic medical condition (that in the opinion of the investigator would make the patient unsuitable for inclusion into the study. * Patient has a history of myopathy, myositis, persistent muscle weakness or persistent high serum CK levels (≥7×ULN), any muscular disease * Patient receiving any drugs potentially associated with myopathy within 3 months prior to screening * Any other clinical significant disease, condition or abnormality, unrelated to their HBV infection at screening, as assessed by the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Achieving Serum HBV DNA Level of <300 Copies/mL (51 IU/mL) at Week 24 | Week 24 | The primary objective of this study was to demonstrate the antiviral efficacy of telbivudine compared to placebo in pediatric patients (2- \< 18 years) by determining the percentage of patients achieving serum HBV DNA level of \<300 copies/mL (51 IU/mL) at Week 24. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Whose Baseline ALTs Were Abnormal and Subsequently Normalized at Week 24, 52 and 104 | Week 24, Week 52, Week 104 | The biochemical response at Weeks 24, 52 and 104 was to be evaluated by the proportion of patients whose baseline ALTs were abnormal (defined as ALT \>1 x Upper Limit of Normal \[ULN\]) and subsequently normalized. Due to early termination of the study and limited number of enrolled patients on track to complete 52 weeks of participation (8 patients overall), only descriptive analysis performed at Week 52 and Week 104. |
| Number of Patients With HBeAg Loss, HBeAg Seroconversion at Week 24, 52 and 104 | Week 24, Week 52, Week 104 | The serological response at Weeks 24, 52 and 104 was to be evaluated by: a) the proportion of HBeAg positive patients at baseline who subsequently have HBeAg loss and HBeAg seroconversion (defined as loss of HBeAg with detectable HBeAb); b) the proportion of HBsAg positive patients at baseline who subsequently have HBsAg loss and HBsAg seroconversion (defined as loss of HBsAg with detectable HBsAb). Due to early termination of the study and limited number of enrolled patients on track to complete 52 weeks of participation (8 patients overall), only descriptive analysis performed at Week 52 and Week 104. |
| Number of Patients With HBsAg Loss, HBsAg Seroconversion at Week 24, 52 and 104 | Week 24, Week 52, Week 104 | The serological response at Weeks 24, 52 and 104 was to be evaluated by: a) the proportion of HBeAg positive patients at baseline who subsequently have HBeAg loss and HBeAg seroconversion (defined as loss of HBeAg with detectable HBeAb); b) the proportion of HBsAg positive patients at baseline who subsequently have HBsAg loss and HBsAg seroconversion (defined as loss of HBsAg with detectable HBsAb). Due to early termination of the study and limited number of enrolled patients on track to complete 52 weeks of participation (8 patients overall), only descriptive analysis performed at Week 52 and Week 104. |
| Number of Patients Achieving HBV DNA< 300 Copies/mL (51 IU/mL) at Week 52 and Week 104 | Week 52, Week 104 | The antiviral efficacy at Weeks 52 and 104 was to be evaluated by: a) the proportion of patients achieving HBV DNA \<300 copies/mL (51 IU/mL) at Week 52 and Week 104; b) the proportion of patients achieving HBV DNA \< Lower Limit of Quantification (LLOQ), \<1000 copies/ml (or 200 IU/mL), \<10,000 copies/ml (or 2 000 IU/mL) and ≥10,000 copies/mL (or 2 000 IU/mL) at Week 24, 52 and 104; c) the proportion of patients achieving Serum HBV DNA reduction from baseline; d) the time to achieve HBV DNA \<300 copies/mL (51 IU/mL); e) the proportion of patients with Primary non-response. Due to early termination of the study and limited number of enrolled patients on track to complete 52 weeks of participation (8 patients overall), only descriptive analysis performed at Week 52 and Week 104. |
| Number of Patients Achieving Cumulative Rate of Virological Breakthrough (VB) at Week 52 and 104 | Week 52, Week 104 | The assessment of virological breakthrough (VB) was to be evaluated by: a) the cumulative rate of patients with confirmed VB at Week 52 and Week 104; b) the time to VB. Due to early termination of the study and limited number of enrolled patients on track to complete 52 weeks of participation (8 patients overall), only descriptive analysis performed at Week 52 and Week 104. |
| Number of Participants With Treatment Emergent Genotypic Resistance Associated With VB, or in Patients With HBV DNA≥300 Copies/mL (51 IU/mL) at Week 24 and Discontinued From the Study | Week 24 | Assessment of the presence of treatment emergent genotypic resistance (confirmed by genotypic sequencing) associated with virological breakthrough over the study period, or in patients with HBV DNA≥300 copies/mL (51 IU/mL) at Week 24 and discontinued from the study treatment (or at discontinuation if prior to Week 24 for subjects with at least 16 weeks of LDT treatment) |
| Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Death | From first dose of study treatment to 30 days after last dose of study treatment, up to 112 weeks | Evaluation of the safety and tolerability of Telbivudine defined by AEs, SAEs, adverse events of special interest (AESI) (including muscle related events) and death; laboratory evaluations specifically on-treatment and post-treatment ALT flares, incidence and clinical significance of CK elevations; growth and development (linear growth and sexual maturation); development of liver decompensation and/or HCC. Only descriptive analysis performed. |
| Number of Patients Achieving a Composite Endpoints (HBV DNA < 300 Copies/mL (51 IU/mL), ALT Normalization and HBeAg Seroconversion) at Week 52 and 104 | Week 52, Week 104 | The proportion of patients achieving composite endpoints at Week 52 and 104 was to be evaluated by the proportion of patients achieving: a) HBV DNA \<300 copies/mL (51 IU/mL); b) ALT normalization and HBeAg seroconversion for HBeAg positive patients only; c) HBV DNA \<300 copies/mL (51 IU/mL) and ALT normalization for HBeAg negative patients. Due to early termination of the study and limited number of enrolled patients on track to complete 52 weeks of participation (8 patients overall), only descriptive analysis performed at Week 52 and Week 104. |
Countries
Bulgaria, Greece, Israel, Romania, South Korea, Turkey (Türkiye), Ukraine
Participant flow
Recruitment details
This study was conducted in 20 centers in 7 countries: Bulgaria (2), Greece (1), Israel (2), Republic of Korea (1), Romania (5), Turkey (4) and Ukraine (5 sites).
Pre-assignment details
Patients were stratified by age group (2 to \< 6 years, 6 to \<12 years and 12 to \<18 years) and HBV DNA level (low and high). At the baseline visit, eligible patients were randomized in a 24-week double blind period to telbivudine or placebo in a ratio 5:1. At Week 24 (visit 6), all patients were unblinded and HBV DNA level were assessed.
Participants by arm
| Arm | Count |
|---|---|
| Telbivudine Patients of any age and weight\< 30kg: telbivudine oral solution (20 mg/mL): 20 mg/kg up to 600 mg q.d corresponding to weight (kg) x1mL, p.o. once daily Patients \< 12 years old and weight≥ 30kg: telbivudine oral solution (20mg/mL), 600 mg/day corresponding to 30 mL p.o. once daily Patients ≥ 12 years old and weight ≥ 30kg: telbivudine film-coated tablet, 600 mg/day, corresponding to 1 tablet p.o. once daily | 43 |
| Placebo Patients of any age and weight \< 30kg: placebo oral solution corresponding to weight (kg) x1mL, p.o. once daily Patients \< 12 years old and weight ≥ 30kg: placebo oral solution corresponding to 30 mL p.o. once daily Patients ≥ 12 years old and weight ≥ 30kg: placebo tablet, corresponding to 1 tablet p.o. once daily. Placebo randomized patients were offered optional telbivudine administration at week 24. | 10 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal Laboratory Values | 0 | 1 |
| Overall Study | Administrative problems | 3 | 3 |
| Overall Study | No longer requires study drug | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Unsatisfactory therapeutic effect | 37 | 4 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Telbivudine | Placebo |
|---|---|---|---|
| Age, Continuous | 10.0 Years STANDARD_DEVIATION 4.86 | 10.2 Years STANDARD_DEVIATION 4.88 | 9.1 Years STANDARD_DEVIATION 4.89 |
| HBV DNA | 8.9 log10 copies/mL STANDARD_DEVIATION 1.43 | 9.1 log10 copies/mL STANDARD_DEVIATION 1.14 | 8.2 log10 copies/mL STANDARD_DEVIATION 2.26 |
| Participants with alanine aminotransferase (ALT) - Multiples of upper limits of normal (ULN) 1 × - < 2 × ULN | 26 Participants | 22 Participants | 4 Participants |
| Participants with alanine aminotransferase (ALT) - Multiples of upper limits of normal (ULN) < 1 × ULN | 7 Participants | 4 Participants | 3 Participants |
| Participants with alanine aminotransferase (ALT) - Multiples of upper limits of normal (ULN) 2 × - < 5 × ULN | 18 Participants | 16 Participants | 2 Participants |
| Participants with alanine aminotransferase (ALT) - Multiples of upper limits of normal (ULN) 5 × or more ULN | 2 Participants | 1 Participants | 1 Participants |
| Participants with aspartate aminotransferase (AST) - Multiples of upper limits of normal (ULN) 1 × - < 2 × ULN | 18 Participants | 14 Participants | 4 Participants |
| Participants with aspartate aminotransferase (AST) - Multiples of upper limits of normal (ULN) < 1 × ULN | 31 Participants | 26 Participants | 5 Participants |
| Participants with aspartate aminotransferase (AST) - Multiples of upper limits of normal (ULN) 2 × - < 5 × ULN | 2 Participants | 2 Participants | 0 Participants |
| Participants with aspartate aminotransferase (AST) - Multiples of upper limits of normal (ULN) 5 × or more ULN | 2 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Caucasian | 50 Participants | 40 Participants | 10 Participants |
| Sex: Female, Male Female | 18 Participants | 14 Participants | 4 Participants |
| Sex: Female, Male Male | 35 Participants | 29 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 43 | 0 / 10 | 0 / 5 | 0 / 48 |
| other Total, other adverse events | 20 / 43 | 4 / 10 | 1 / 5 | 21 / 48 |
| serious Total, serious adverse events | 0 / 43 | 0 / 10 | 0 / 5 | 0 / 48 |
Outcome results
Primary
Number of Patients Achieving Serum HBV DNA Level of <300 Copies/mL (51 IU/mL) at Week 24
The primary objective of this study was to demonstrate the antiviral efficacy of telbivudine compared to placebo in pediatric patients (2- \< 18 years) by determining the percentage of patients achieving serum HBV DNA level of \<300 copies/mL (51 IU/mL) at Week 24.
Time frame: Week 24
Population: The Full Analysis Set (FAS), which consisted of all randomized patients to whom study treatment had been assigned, was considered.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Telbivudine | Number of Patients Achieving Serum HBV DNA Level of <300 Copies/mL (51 IU/mL) at Week 24 | 5 Participants |
| Placebo | Number of Patients Achieving Serum HBV DNA Level of <300 Copies/mL (51 IU/mL) at Week 24 | 1 Participants |
Comparison: HBV DNA level of \<300 copies/mL (51 IU/mL) at Week 24p-value: 195% CI: [-37.03, 36.75]Fisher Exact
Secondary
Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Death
Evaluation of the safety and tolerability of Telbivudine defined by AEs, SAEs, adverse events of special interest (AESI) (including muscle related events) and death; laboratory evaluations specifically on-treatment and post-treatment ALT flares, incidence and clinical significance of CK elevations; growth and development (linear growth and sexual maturation); development of liver decompensation and/or HCC. Only descriptive analysis performed.
Time frame: From first dose of study treatment to 30 days after last dose of study treatment, up to 112 weeks
Population: The Safety Set, which consisted of all patients who received at least one dose of study drug during the treatment period, was considered.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Telbivudine | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Death | On-treatment Adverse Event (AEs) | 20 Participants |
| Telbivudine | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Death | On-treatment Serious Adverse Event (SAEs) | 0 Participants |
| Telbivudine | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Death | On-treatment Deaths | 0 Participants |
| Placebo | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Death | On-treatment Adverse Event (AEs) | 4 Participants |
| Placebo | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Death | On-treatment Serious Adverse Event (SAEs) | 0 Participants |
| Placebo | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Death | On-treatment Deaths | 0 Participants |
Secondary
Number of Participants With Treatment Emergent Genotypic Resistance Associated With VB, or in Patients With HBV DNA≥300 Copies/mL (51 IU/mL) at Week 24 and Discontinued From the Study
Assessment of the presence of treatment emergent genotypic resistance (confirmed by genotypic sequencing) associated with virological breakthrough over the study period, or in patients with HBV DNA≥300 copies/mL (51 IU/mL) at Week 24 and discontinued from the study treatment (or at discontinuation if prior to Week 24 for subjects with at least 16 weeks of LDT treatment)
Time frame: Week 24
Population: The Full Analysis Set (FAS), which consisted of all randomized patients to whom study treatment had been assigned, was considered. Only patients with efficacy data within censoring date included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Telbivudine | Number of Participants With Treatment Emergent Genotypic Resistance Associated With VB, or in Patients With HBV DNA≥300 Copies/mL (51 IU/mL) at Week 24 and Discontinued From the Study | Cumulative virological breakthrough | 0 Participants |
| Telbivudine | Number of Participants With Treatment Emergent Genotypic Resistance Associated With VB, or in Patients With HBV DNA≥300 Copies/mL (51 IU/mL) at Week 24 and Discontinued From the Study | Cumulative treatment emergent genotypic resistance | 1 Participants |
| Placebo | Number of Participants With Treatment Emergent Genotypic Resistance Associated With VB, or in Patients With HBV DNA≥300 Copies/mL (51 IU/mL) at Week 24 and Discontinued From the Study | Cumulative virological breakthrough | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Genotypic Resistance Associated With VB, or in Patients With HBV DNA≥300 Copies/mL (51 IU/mL) at Week 24 and Discontinued From the Study | Cumulative treatment emergent genotypic resistance | 0 Participants |
Comparison: Treatment emergent genotypic resistance at Week 24p-value: 195% CI: [-37.05, 41.83]Fisher Exact
Secondary
Number of Patients Achieving a Composite Endpoints (HBV DNA < 300 Copies/mL (51 IU/mL), ALT Normalization and HBeAg Seroconversion) at Week 52 and 104
The proportion of patients achieving composite endpoints at Week 52 and 104 was to be evaluated by the proportion of patients achieving: a) HBV DNA \<300 copies/mL (51 IU/mL); b) ALT normalization and HBeAg seroconversion for HBeAg positive patients only; c) HBV DNA \<300 copies/mL (51 IU/mL) and ALT normalization for HBeAg negative patients. Due to early termination of the study and limited number of enrolled patients on track to complete 52 weeks of participation (8 patients overall), only descriptive analysis performed at Week 52 and Week 104.
Time frame: Week 52, Week 104
Population: The Full Analysis Set (FAS), which consisted of all randomized patients to whom study treatment had been assigned, was considered. Only patients with efficacy data within censoring date included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Telbivudine | Number of Patients Achieving a Composite Endpoints (HBV DNA < 300 Copies/mL (51 IU/mL), ALT Normalization and HBeAg Seroconversion) at Week 52 and 104 | Week 52 | 1 Participants |
| Telbivudine | Number of Patients Achieving a Composite Endpoints (HBV DNA < 300 Copies/mL (51 IU/mL), ALT Normalization and HBeAg Seroconversion) at Week 52 and 104 | Week 104 | 1 Participants |
| Placebo | Number of Patients Achieving a Composite Endpoints (HBV DNA < 300 Copies/mL (51 IU/mL), ALT Normalization and HBeAg Seroconversion) at Week 52 and 104 | Week 52 | 0 Participants |
Secondary
Number of Patients Achieving Cumulative Rate of Virological Breakthrough (VB) at Week 52 and 104
The assessment of virological breakthrough (VB) was to be evaluated by: a) the cumulative rate of patients with confirmed VB at Week 52 and Week 104; b) the time to VB. Due to early termination of the study and limited number of enrolled patients on track to complete 52 weeks of participation (8 patients overall), only descriptive analysis performed at Week 52 and Week 104.
Time frame: Week 52, Week 104
Population: The Full Analysis Set (FAS), which consisted of all randomized patients to whom study treatment had been assigned, was considered. Only patients with efficacy data within censoring date included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Telbivudine | Number of Patients Achieving Cumulative Rate of Virological Breakthrough (VB) at Week 52 and 104 | Week 52 | 1 Participants |
| Telbivudine | Number of Patients Achieving Cumulative Rate of Virological Breakthrough (VB) at Week 52 and 104 | Week 104 | 1 Participants |
| Placebo | Number of Patients Achieving Cumulative Rate of Virological Breakthrough (VB) at Week 52 and 104 | Week 52 | 0 Participants |
| Placebo | Number of Patients Achieving Cumulative Rate of Virological Breakthrough (VB) at Week 52 and 104 | Week 104 | 0 Participants |
Secondary
Number of Patients Achieving HBV DNA< 300 Copies/mL (51 IU/mL) at Week 52 and Week 104
The antiviral efficacy at Weeks 52 and 104 was to be evaluated by: a) the proportion of patients achieving HBV DNA \<300 copies/mL (51 IU/mL) at Week 52 and Week 104; b) the proportion of patients achieving HBV DNA \< Lower Limit of Quantification (LLOQ), \<1000 copies/ml (or 200 IU/mL), \<10,000 copies/ml (or 2 000 IU/mL) and ≥10,000 copies/mL (or 2 000 IU/mL) at Week 24, 52 and 104; c) the proportion of patients achieving Serum HBV DNA reduction from baseline; d) the time to achieve HBV DNA \<300 copies/mL (51 IU/mL); e) the proportion of patients with Primary non-response. Due to early termination of the study and limited number of enrolled patients on track to complete 52 weeks of participation (8 patients overall), only descriptive analysis performed at Week 52 and Week 104.
Time frame: Week 52, Week 104
Population: The Full Analysis Set (FAS), which consisted of all randomized patients to whom study treatment had been assigned, was considered. Only patients with efficacy data within censoring date included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Telbivudine | Number of Patients Achieving HBV DNA< 300 Copies/mL (51 IU/mL) at Week 52 and Week 104 | Week 52 | 3 Participants |
| Telbivudine | Number of Patients Achieving HBV DNA< 300 Copies/mL (51 IU/mL) at Week 52 and Week 104 | Week 104 | 2 Participants |
| Placebo | Number of Patients Achieving HBV DNA< 300 Copies/mL (51 IU/mL) at Week 52 and Week 104 | Week 52 | 0 Participants |
Secondary
Number of Patients Whose Baseline ALTs Were Abnormal and Subsequently Normalized at Week 24, 52 and 104
The biochemical response at Weeks 24, 52 and 104 was to be evaluated by the proportion of patients whose baseline ALTs were abnormal (defined as ALT \>1 x Upper Limit of Normal \[ULN\]) and subsequently normalized. Due to early termination of the study and limited number of enrolled patients on track to complete 52 weeks of participation (8 patients overall), only descriptive analysis performed at Week 52 and Week 104.
Time frame: Week 24, Week 52, Week 104
Population: The Full Analysis Set (FAS), which consisted of all randomized patients to whom study treatment had been assigned, was considered. Only patients with efficacy data within censoring date included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Telbivudine | Number of Patients Whose Baseline ALTs Were Abnormal and Subsequently Normalized at Week 24, 52 and 104 | Week 24 | 12 Participants |
| Telbivudine | Number of Patients Whose Baseline ALTs Were Abnormal and Subsequently Normalized at Week 24, 52 and 104 | Week 52 | 1 Participants |
| Telbivudine | Number of Patients Whose Baseline ALTs Were Abnormal and Subsequently Normalized at Week 24, 52 and 104 | Week 104 | 2 Participants |
| Placebo | Number of Patients Whose Baseline ALTs Were Abnormal and Subsequently Normalized at Week 24, 52 and 104 | Week 24 | 0 Participants |
| Placebo | Number of Patients Whose Baseline ALTs Were Abnormal and Subsequently Normalized at Week 24, 52 and 104 | Week 52 | 1 Participants |
Comparison: ALT levels at Week 24p-value: 0.298495% CI: [-14.62, 74.6]Fisher Exact
Secondary
Number of Patients With HBeAg Loss, HBeAg Seroconversion at Week 24, 52 and 104
The serological response at Weeks 24, 52 and 104 was to be evaluated by: a) the proportion of HBeAg positive patients at baseline who subsequently have HBeAg loss and HBeAg seroconversion (defined as loss of HBeAg with detectable HBeAb); b) the proportion of HBsAg positive patients at baseline who subsequently have HBsAg loss and HBsAg seroconversion (defined as loss of HBsAg with detectable HBsAb). Due to early termination of the study and limited number of enrolled patients on track to complete 52 weeks of participation (8 patients overall), only descriptive analysis performed at Week 52 and Week 104.
Time frame: Week 24, Week 52, Week 104
Population: The Full Analysis Set (FAS), which consisted of all randomized patients to whom study treatment had been assigned, was considered. Only patients with efficacy data within censoring date included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Telbivudine | Number of Patients With HBeAg Loss, HBeAg Seroconversion at Week 24, 52 and 104 | HBeAg loss at Week 24 | 1 Participants |
| Telbivudine | Number of Patients With HBeAg Loss, HBeAg Seroconversion at Week 24, 52 and 104 | HBeAg loss at Week 52 | 1 Participants |
| Telbivudine | Number of Patients With HBeAg Loss, HBeAg Seroconversion at Week 24, 52 and 104 | HBeAg seroconversion at Week 52 | 1 Participants |
| Telbivudine | Number of Patients With HBeAg Loss, HBeAg Seroconversion at Week 24, 52 and 104 | HBeAg loss at Week 104 | 1 Participants |
| Telbivudine | Number of Patients With HBeAg Loss, HBeAg Seroconversion at Week 24, 52 and 104 | HBeAg seroconversion at Week 104 | 1 Participants |
| Telbivudine | Number of Patients With HBeAg Loss, HBeAg Seroconversion at Week 24, 52 and 104 | HBeAg seroconversion at Week 24 | 1 Participants |
| Placebo | Number of Patients With HBeAg Loss, HBeAg Seroconversion at Week 24, 52 and 104 | HBeAg loss at Week 24 | 0 Participants |
| Placebo | Number of Patients With HBeAg Loss, HBeAg Seroconversion at Week 24, 52 and 104 | HBeAg loss at Week 52 | 0 Participants |
| Placebo | Number of Patients With HBeAg Loss, HBeAg Seroconversion at Week 24, 52 and 104 | HBeAg seroconversion at Week 24 | 0 Participants |
| Placebo | Number of Patients With HBeAg Loss, HBeAg Seroconversion at Week 24, 52 and 104 | HBeAg seroconversion at Week 52 | 0 Participants |
Comparison: HBeAg loss at Week 24p-value: 195% CI: [-53.7, 60.2]Fisher Exact
Comparison: HBeAg seroconversion at Week 24p-value: 195% CI: [-53.7, 60.2]Fisher Exact
Secondary
Number of Patients With HBsAg Loss, HBsAg Seroconversion at Week 24, 52 and 104
The serological response at Weeks 24, 52 and 104 was to be evaluated by: a) the proportion of HBeAg positive patients at baseline who subsequently have HBeAg loss and HBeAg seroconversion (defined as loss of HBeAg with detectable HBeAb); b) the proportion of HBsAg positive patients at baseline who subsequently have HBsAg loss and HBsAg seroconversion (defined as loss of HBsAg with detectable HBsAb). Due to early termination of the study and limited number of enrolled patients on track to complete 52 weeks of participation (8 patients overall), only descriptive analysis performed at Week 52 and Week 104.
Time frame: Week 24, Week 52, Week 104
Population: The Full Analysis Set (FAS), which consisted of all randomized patients to whom study treatment had been assigned, was considered. Only patients with efficacy data within censoring date included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Telbivudine | Number of Patients With HBsAg Loss, HBsAg Seroconversion at Week 24, 52 and 104 | HBsAg loss at Week 24 | 1 Participants |
| Telbivudine | Number of Patients With HBsAg Loss, HBsAg Seroconversion at Week 24, 52 and 104 | HBsAg loss at Week 52 | 0 Participants |
| Telbivudine | Number of Patients With HBsAg Loss, HBsAg Seroconversion at Week 24, 52 and 104 | HBsAg seroconversion at Week 52 | 0 Participants |
| Telbivudine | Number of Patients With HBsAg Loss, HBsAg Seroconversion at Week 24, 52 and 104 | HBsAg loss at Week 104 | 0 Participants |
| Telbivudine | Number of Patients With HBsAg Loss, HBsAg Seroconversion at Week 24, 52 and 104 | HBsAg seroconversion at Week 104 | 0 Participants |
| Telbivudine | Number of Patients With HBsAg Loss, HBsAg Seroconversion at Week 24, 52 and 104 | HBsAg seroconversion at Week 24 | 0 Participants |
| Placebo | Number of Patients With HBsAg Loss, HBsAg Seroconversion at Week 24, 52 and 104 | HBsAg loss at Week 24 | 0 Participants |
| Placebo | Number of Patients With HBsAg Loss, HBsAg Seroconversion at Week 24, 52 and 104 | HBsAg loss at Week 52 | 0 Participants |
| Placebo | Number of Patients With HBsAg Loss, HBsAg Seroconversion at Week 24, 52 and 104 | HBsAg seroconversion at Week 24 | 0 Participants |
| Placebo | Number of Patients With HBsAg Loss, HBsAg Seroconversion at Week 24, 52 and 104 | HBsAg seroconversion at Week 52 | 0 Participants |
Comparison: HBsAg loss at Week 24p-value: 195% CI: [-37.54, 42.17]Fisher Exact