Clinical trial NCT02058108: Study of Efficacy and Safety, Tolerability and Pharmacokinetics of Telbivudine in Children and Adolescents With Compensated Chronic Hepatitis B Virus Infection
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Chronic Hepatitis B
Keywords: Chronic hepatitis B, pediatrics, antiviral treatment, telbivudine
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-02-07
Enrollment: 53
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Patients Achieving Serum HBV DNA Level of <300 Copies/mL (51 IU/mL) at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Number of Patients Achieving HBV DNA< 300 Copies/mL (51 IU/mL) at Week 52 and Week 104
timeFrame: Week 52, Week 104
measure: Number of Patients Whose Baseline ALTs Were Abnormal and Subsequently Normalized at Week 24, 52 and 104
timeFrame: Week 24, Week 52, Week 104
measure: Number of Patients With HBeAg Loss, HBeAg Seroconversion at Week 24, 52 and 104
timeFrame: Week 24, Week 52, Week 104
measure: Number of Patients With HBsAg Loss, HBsAg Seroconversion at Week 24, 52 and 104
timeFrame: Week 24, Week 52, Week 104
measure: 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
timeFrame: Week 52, Week 104
measure: Number of Patients Achieving Cumulative Rate of Virological Breakthrough (VB) at Week 52 and 104
timeFrame: Week 52, Week 104
measure: 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
timeFrame: Week 24
measure: Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Death
timeFrame: From first dose of study treatment to 30 days after last dose of study treatment, up to 112 weeks
Other outcomes:
Locations:
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
state: Sofia-Grad
city: Pleven
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Varna
country: Bulgaria
facility: Novartis Investigative Site
city: Goudi-Athens
country: Greece
facility: Novartis Investigative Site
state: GR
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Jerusalem
country: Israel
facility: Novartis Investigative Site
city: Jerusalem
country: Israel
facility: Novartis Investigative Site
city: Nahariya
country: Israel
facility: Novartis Investigative Site
city: Nazareth
country: Israel
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Cluj Napoca
country: Romania
facility: Novartis Investigative Site
state: Cluj
city: Craiova
country: Romania
facility: Novartis Investigative Site
state: Dolj
city: Timisoara
country: Romania
facility: Novartis Investigative Site
state: Jud. Timis
city: Bucharest
country: Romania
facility: Novartis Investigative Site
city: Bucharest
country: Romania
facility: Novartis Investigative Site
city: Bucharest
country: Romania
facility: Novartis Investigative Site
city: Iasi
country: Romania
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Antalya
country: Turkey
facility: Novartis Investigative Site
city: Diyarbakir
country: Turkey
facility: Novartis Investigative Site
city: Elazig
country: Turkey
facility: Novartis Investigative Site
city: Eskisehir
country: Turkey
facility: Novartis Investigative Site
city: Mersin
country: Turkey
facility: Novartis Investigative Site
city: Dnipropetrovsk
country: Ukraine
facility: Novartis Investigative Site
city: Kiev
country: Ukraine
facility: Novartis Investigative Site
city: Kyiv
country: Ukraine
facility: Novartis Investigative Site
city: Odesa
country: Ukraine
facility: Novartis Investigative Site
city: Vinnytsia
country: Ukraine
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: