Trial record 115 of 442 for:    hepatitis b | Open Studies

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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified July 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT02058108
First received: February 5, 2014
Last updated: July 22, 2014
Last verified: July 2014
  Purpose

The purpose of the study is 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 is part of the commitments of the pediatric development plan for telbivudine in Europe and US.


Condition Intervention Phase
Chronic Hepatitis B
Drug: Telbivudine
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Antiviral efficacy of telbivudine compared to placebo in pediatric patients (2- < 18 years) (percentage of patients achieving serum HBV DNA level of <300 copies/mL (51 IU/mL)) at Week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    The primary objective of this study is 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 Outcome Measures:
  • Antiviral efficacy (proportion of patients achieving HBV DNA< 300 copies/mL (51 IU/mL)) at Week 52 and Week 104 [ Time Frame: 52 weeks,104 weeks ] [ Designated as safety issue: No ]
    Assessment of antiviral efficacy evaluated by: Proportion of patients achieving HBV DNA <300 copies/mL (51 IU/mL) at Week 52 and Week 104. 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. Serum HBV DNA reduction from baseline. Time to achieve HBV DNA <300 copies/mL (51 IU/mL). Proportion of patients with Primary non-response

  • Biochemical response (proportion of patients whose baseline ALTs were abnormal and subsequently normalized) at Week 24, 52 and 104 [ Time Frame: 24 weeks, 52 weeks, 104 weeks ] [ Designated as safety issue: No ]
    Assessment of the biochemical response at Week 24, 52 and 104 as evaluated by proportion of patients whose baseline ALTs were abnormal (defined as ALT >1 x Upper Limit of Normal [ULN]) and subsequently normalized

  • Serological response (proportion of patients with HBeAg loss, HBeAg seroconversion and HBsAg loss, HBsAg seroconversion) at Week 24, 52 and 104 [ Time Frame: 24 weeks, 52 weeks, 104 weeks ] [ Designated as safety issue: No ]
    The serological responses at Week 24, 52 and 104 is evaluated by: Proportion of HBeAg positive patients at baseline who subsequently have HBeAg loss and HBeAg seroconversion (defined as loss of HBeAg with detectable HBeAb). Proportion of HBsAg positive patients at baseline who subsequently have HBsAg loss and HBsAg seroconversion (defined as loss of HBsAg with detectable HBsAb)

  • Proportion of patients achieving a composite endpoints (HBV DNA < 300 copies/mL (51 IU/mL), ALT normalization and HBeAg seroconversion) at Week 52 and 104 [ Time Frame: 52 weeks, 104 weeks ] [ Designated as safety issue: No ]

    Percentage of patients achieving composite endpoints at Week 52 and 104:

    HBV DNA <300 copies/mL (51 IU/mL), ALT normalization and HBeAg seroconversion for HBeAg positive patients only HBV DNA <300 copies/mL (51 IU/mL) and ALT normalization for HBeAg negative patients


  • The cumulative rate of virological breakthrough (VB) at Week 52 and 104 [ Time Frame: 52 weeks, 104 weeks ] [ Designated as safety issue: No ]
    Assessment of virological breakthrough (VB) as evaluated by: Cumulative rate of patients with confirmed VB at Week 52 and Week 104; and Time to VB

  • Presence of 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 [ Time Frame: 52 weeks, 104 weeks ] [ Designated as safety issue: No ]
    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)

  • Safety and tolerability of telbivudine at Week 52 and 104 [ Time Frame: 52 weeks, 104 weeks ] [ Designated as safety issue: Yes ]
    Evaluation of the safety and tolerability of telbivudine at Week 52 and 104 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


Other Outcome Measures:
  • Evaluation of the population pharmacokinetics of telbivudine in pediatric patients [ Time Frame: 4 weeks, 12 weeks, 16 weeks and 24 weeks ] [ Designated as safety issue: No ]
    A population pharmacokinetic (population PK) study will be performed using a sparse sampling technique for all patients in the LDT600 treatment group. These sparse samples will be used together with the existing extensive sampling pharmacokinetic data from Phase I study to build a population PK model in pediatric patients. The objectives for performing the population PK assessments are to characterize LDT600 PK profiles and estimate exposure (e.g. AUC, Cmax and Cmin) at the steady-state among different age and disease groups of children as compared to adults.

  • Evaluation of the palatability of telbivudine oral solution [ Time Frame: 104 weeks ] [ Designated as safety issue: No ]
    Question asked to the patients receiving oral solution to assess the taste of telbivudine solution


Estimated Enrollment: 150
Study Start Date: August 2014
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Drug: 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
Placebo Comparator: 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
Drug: 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

  Eligibility

Ages Eligible for Study:   2 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Clinical history compatible with compensated chronic hepatitis B
  • Documented compensated chronic hepatitis B defined by the following:

oPositive serum HBsAg at screening and at least one other documentation of HBsAg positive at least 6 months prior to screening oFor 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 oFor 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02058108

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

  Show 42 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02058108     History of Changes
Other Study ID Numbers: CLDT600A2306
Study First Received: February 5, 2014
Last Updated: July 22, 2014
Health Authority: United States: Food and Drug Administration; Europe: European Medicines Agency

Keywords provided by Novartis:
Chronic hepatitis B, pediatrics, antiviral treatment, telbivudine

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
Hepatitis B, Chronic
Hepatitis, Viral, Human
Virus Diseases
Liver Diseases
Digestive System Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Pharmaceutical Solutions
Telbivudine
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 21, 2014