A Randomized, Double-blind, 104-weeks Treatment Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Telbivudine Oral Solution and Tablets in Children and Adolescents With Compensated HBeAg-positive and Negative Chronic Hepatitis B Virus Infection
Overview
- Phase
- Phase 3
- Intervention
- Telbivudine
- Conditions
- Chronic Hepatitis B
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 53
- Locations
- 1
- Primary Endpoint
- Number of Patients Achieving Serum HBV DNA Level of <300 Copies/mL (51 IU/mL) at Week 24
- Status
- Terminated
- Last Updated
- 6 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Clinical history compatible with compensated chronic hepatitis B
- •Documented compensated chronic hepatitis B defined by the following:
- •Positive serum HBsAg at screening and at least one other documentation of HBsAg positive at least 6 months prior to screening
- •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
- •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)
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
Arms & Interventions
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
Intervention: Telbivudine
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
Intervention: Placebo
Outcomes
Primary Outcomes
Number of Patients Achieving Serum HBV DNA Level of <300 Copies/mL (51 IU/mL) at Week 24
Time Frame: 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 Outcomes
- Number of Patients With HBsAg Loss, HBsAg Seroconversion at Week 24, 52 and 104(Week 24, Week 52, Week 104)
- 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)
- Number of Patients Achieving HBV DNA< 300 Copies/mL (51 IU/mL) at Week 52 and Week 104(Week 52, Week 104)
- Number of Patients With HBeAg Loss, HBeAg Seroconversion at Week 24, 52 and 104(Week 24, Week 52, Week 104)
- Number of Patients Whose Baseline ALTs Were Abnormal and Subsequently Normalized at Week 24, 52 and 104(Week 24, Week 52, Week 104)
- Number of Patients Achieving Cumulative Rate of Virological Breakthrough (VB) at Week 52 and 104(Week 52, 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)
- 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)