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

NCT02058108 | Terminated Phase 3 Results DMC

• 2 other identifiers: CLDT600A23062012-004942-14
• Study Type: interventional
• Target: 53
• Locations: 7 countries
• Sites: 29

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.

Conditions

Chronic Hepatitis B

Keywords

Chronic hepatitis B, pediatrics, antiviral treatment, telbivudine

Outcome Measures

Primary Outcomes (1)

• 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.

  Week 24

Secondary Outcomes (8)

• Number of Patients Achieving HBV DNA< 300 Copies/mL (51 IU/mL) at Week 52 and Week 104

  Week 52, Week 104

• Number of Patients Whose Baseline ALTs Were Abnormal and Subsequently Normalized at Week 24, 52 and 104

  Week 24, Week 52, Week 104

• Number of Patients With HBeAg Loss, HBeAg Seroconversion at Week 24, 52 and 104

  Week 24, Week 52, Week 104

• Number of Patients With HBsAg Loss, HBsAg Seroconversion at Week 24, 52 and 104

  Week 24, Week 52, Week 104

• 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

  Week 52, Week 104

Study Arms (2)

Telbivudine

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Telbivudine DRUG

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

Telbivudine

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (29)

Novartis Investigative Site

Sofia, Sofia-Grad, 1700, Bulgaria

Location

Novartis Investigative Site

Pleven, 5800, Bulgaria

Location

Novartis Investigative Site

Sofia, 1407, Bulgaria

Location

Novartis Investigative Site

Varna, 9010, Bulgaria

Location

Novartis Investigative Site

Goudi-Athens, GR, 115 27, Greece

Location

Novartis Investigative Site

Athens, 12462, Greece

Location

Novartis Investigative Site

Jerusalem, 91031, Israel

Location

Novartis Investigative Site

Jerusalem, 91120, Israel

Location

Novartis Investigative Site

Nahariya, 22100, Israel

Location

Novartis Investigative Site

Nazareth, 16100, Israel

Location

Novartis Investigative Site

Cluj-Napoca, Cluj, 400177, Romania

Location

Novartis Investigative Site

Craiova, Dolj, 200515, Romania

Location

Novartis Investigative Site

Timișoara, Jud. Timis, 300011, Romania

Location

Novartis Investigative Site

Bucharest, 011743, Romania

Location

Novartis Investigative Site

Bucharest, 021105, Romania

Location

Novartis Investigative Site

Bucharest, 022328, Romania

Location

Novartis Investigative Site

Iași, 700309, Romania

Location

Novartis Investigative Site

Seoul, Korea, 05505, South Korea

Location

Novartis Investigative Site

Ankara, 06100, Turkey (Türkiye)

Location

Novartis Investigative Site

Antalya, 07070, Turkey (Türkiye)

Location

Novartis Investigative Site

Diyarbakır, 21000, Turkey (Türkiye)

Location

Novartis Investigative Site

Elâzığ, 23119, Turkey (Türkiye)

Location

Novartis Investigative Site

Eskişehir, 26040, Turkey (Türkiye)

Location

Novartis Investigative Site

Mersin, 33343, Turkey (Türkiye)

Location

Novartis Investigative Site

Dnipropetrovsk, 49006, Ukraine

Location

Novartis Investigative Site

Kiev, Ukraine

Location

Novartis Investigative Site

Kyiv, 04119, Ukraine

Location

Novartis Investigative Site

Odesa, 65031, Ukraine

Location

Novartis Investigative Site

Vinnytsia, 21029, Ukraine

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

Telbivudine

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

Due to early termination of the study and limited number of enrolled patients on track to complete 52 weeks of participation (8 patients overall), no formal analysis of Weeks 52 and 104 long-term efficacy endpoints (only descriptive analysis).

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2014
• First Posted: February 7, 2014
• Study Start: October 31, 2014
• Primary Completion: January 9, 2019
• Study Completion: January 9, 2019
• Last Updated: September 10, 2019
• Results First Posted: September 10, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will share

Locations

UA (5); BU (4); TU (6); GR (2); RO (7); IL (4); KR (1)