Study of Efficacy and Safety, Tolerability and Pharmacokinetics of Telbivudine in Children and Adolescents With Compensated Chronic Hepatitis B Virus Infection

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

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.

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