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

Phase 3TerminatedNCT02058108

Novartis Pharmaceuticals53 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Chronic Hepatitis B

Interventions

TelbivudineDRUG

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

PlaceboDRUG

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

Eligibility

Sex: ALLMin age: 2 YearsMax age: 17 Years

Medical Language ↔ Plain English

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

Locations (29)

Novartis Investigative Site

Outcomes

Primary Outcomes

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

Secondary Outcomes

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

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

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.

Data from ClinicalTrials.gov

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