- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02058108
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
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Pleven, Bulgaria, 5800
- Novartis Investigative Site
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Sofia, Bulgaria, 1407
- Novartis Investigative Site
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Varna, Bulgaria, 9010
- Novartis Investigative Site
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Sofia-Grad
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Sofia, Sofia-Grad, Bulgaria, 1700
- Novartis Investigative Site
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Athens, Greece, 12462
- Novartis Investigative Site
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GR
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Goudi-Athens, GR, Greece, 115 27
- Novartis Investigative Site
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Jerusalem, Israel, 91120
- Novartis Investigative Site
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Jerusalem, Israel, 91031
- Novartis Investigative Site
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Nahariya, Israel, 22100
- Novartis Investigative Site
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Nazareth, Israel, 16100
- Novartis Investigative Site
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Korea
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Seoul, Korea, Korea, Republic of, 05505
- Novartis Investigative Site
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Bucharest, Romania, 022328
- Novartis Investigative Site
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Bucharest, Romania, 011743
- Novartis Investigative Site
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Bucharest, Romania, 021105
- Novartis Investigative Site
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Iasi, Romania, 700309
- Novartis Investigative Site
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Cluj
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Cluj Napoca, Cluj, Romania, 400177
- Novartis Investigative Site
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Dolj
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Craiova, Dolj, Romania, 200515
- Novartis Investigative Site
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Jud. Timis
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Timisoara, Jud. Timis, Romania, 300011
- Novartis Investigative Site
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Ankara, Turkey, 06100
- Novartis Investigative Site
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Antalya, Turkey, 07070
- Novartis Investigative Site
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Diyarbakir, Turkey, 21000
- Novartis Investigative Site
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Elazig, Turkey, 23119
- Novartis Investigative Site
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Eskisehir, Turkey, 26040
- Novartis Investigative Site
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Mersin, Turkey, 33343
- Novartis Investigative Site
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Dnipropetrovsk, Ukraine, 49006
- Novartis Investigative Site
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Kiev, Ukraine
- Novartis Investigative Site
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Kyiv, Ukraine, 04119
- Novartis Investigative Site
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Odesa, Ukraine, 65031
- Novartis Investigative Site
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Vinnytsia, Ukraine, 21029
- Novartis Investigative Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Key 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)
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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
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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
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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
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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
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Patients Achieving Serum HBV DNA Level of <300 Copies/mL (51 IU/mL) at Week 24
Time Frame: Week 24
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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.
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Week 24
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Patients Achieving HBV DNA< 300 Copies/mL (51 IU/mL) at Week 52 and Week 104
Time Frame: Week 52, Week 104
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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. |
Week 52, Week 104
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Number of Patients Whose Baseline ALTs Were Abnormal and Subsequently Normalized at Week 24, 52 and 104
Time Frame: Week 24, Week 52, Week 104
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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. |
Week 24, Week 52, Week 104
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Number of Patients With HBeAg Loss, HBeAg Seroconversion at Week 24, 52 and 104
Time Frame: Week 24, Week 52, Week 104
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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. |
Week 24, Week 52, Week 104
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Number of Patients With HBsAg Loss, HBsAg Seroconversion at Week 24, 52 and 104
Time Frame: Week 24, Week 52, Week 104
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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. |
Week 24, Week 52, Week 104
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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
Time Frame: Week 52, Week 104
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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. |
Week 52, Week 104
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Number of Patients Achieving Cumulative Rate of Virological Breakthrough (VB) at Week 52 and 104
Time Frame: Week 52, Week 104
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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. |
Week 52, Week 104
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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
Time Frame: Week 24
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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)
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Week 24
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Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Death
Time Frame: From first dose of study treatment to 30 days after last dose of study treatment, up to 112 weeks
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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. |
From first dose of study treatment to 30 days after last dose of study treatment, up to 112 weeks
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- RNA Virus Infections
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Liver Diseases
- Hepatitis, Viral, Human
- Hepadnaviridae Infections
- DNA Virus Infections
- Enterovirus Infections
- Picornaviridae Infections
- Hepatitis B
- Hepatitis
- Hepatitis A
- Virus Diseases
- Hepatitis B, Chronic
- Hepatitis, Chronic
- Herpesviridae Infections
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Telbivudine
Other Study ID Numbers
- CLDT600A2306
- 2012-004942-14 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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