Study of efficacy and safety, tolerability and pharmacokinetics of telbivudine in children and adolescents with compensated chronic hepatitis B virus infection

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2012-004942-14-BG
• Date of registration: 09/06/2014
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Study of efficacy and safety, tolerability and pharmacokinetics of telbivudine in children and adolescents with compensated chronic hepatitis B virus infection
• Scientific 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 P/119/2010 P/203/2011 P/236/2012
• Date of first enrolment: 29/10/2014
• Target sample size: 150
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-004942-14
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, Greece, Israel, Korea, Republic of, Romania, Taiwan, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Hassan Gandjini
• Affiliation: PPD

• Name: Hassan Gandjini
• Affiliation: PPD

Key inclusion & exclusion criteria

Inclusion criteria:
1. A signed informed constent/assent must have been obtenined from
both parents or legal guardian(s) before any assessment is performed
2. Male or female out-patients between 2 and < 18 years of age (at time
of randomization), except in the Republic of South Korea, where children
aged 2 years to < 12 years only (at time of randomization) will be
enrolled
3. Clinical history compatible with compensated chronic hepatitis B
4. Documented compensated chronic hepatitis B defined by the following:
a) Positive serum HBsAg at screening and at least one other documentation of HBsAg positive at least 6 months prior to screening
b) For HBeAg positive patients at screening, significant biologic signs of disease activity following EASL guidelines recommendations for CHB pediatric patients (Sokal et al 2013)
i) serum HBV DNA level = 5 log10 copies/mL (COBAS Taqman®) (or 20
000 IU/mL) at screeningas assesed by central laboratory and
ii) serum ALT = 1.5×ULN and < 10×ULN (pediatric ULN) either once
during the screening period or twice (2 times)within 6 months prior to
screening
c) For HBeAg negative patients at screening, significant biologic signs of disease activity following EASL guidelines recommendations for CHB pediatric patients (Sokal et al 2013)
i) serum HBV DNA level = 4 log10 copies/mL (COBAS Taqman®) or 2000 IU/ml at screening as assessed by the central laboratory and
ii) serum ALT = 1.0 ×ULN and < 10×ULN (pediatric ULN) either once during the screening period or twice (2times) within 12 months prior to screening
5. Patients and parent (or legal guardian) are willing to comply with the
study drug regimen and all other study requirements.
6. Patient meeting criteria for treatment according to local guidelines.
Are the trial subjects under 18? yes
Number of subjects for this age range: 150
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
•Patients with acute or chronic infection of HCV, HDV, HIV, or with acute infection of HAV, HEV, CMV, or EBV.
•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 (topical and inhaled corticosteroids are allowed).
• Patient has a decompensated liver disease defined as a Child-Turcotte-Pugh (CTP) Score =7 (Class B or C).
•Patient has one or more additional known primary or secondary causes of liver disease, other than infectious agents, including alcoholic or nonalcoholic liver disease, fatty liver,
hepatobiliary disease, Wilson disease and alpha-1 antitrypsin deficiency, Gilbert's syndrome, Dubin-Johnson syndrome etc.
• Liver transplant recipient. Organ or bone marrow transplant recipients.
• Patient is currently abusing illicit drugs, or has a history of illicit substance abuse.
• All patients are required to be abstinent from alcohol during the course of the study otherwise excluded.
• Patient has a medical condition requiring the chronic or prolonged use of potentially hepatotoxic drugs or nephrotoxic drugs or chemotherapy
• History of any other acute or chronic medical condition ( including congenital diseases, metabolic diseases, malignant diseases, neurological disorders, nephrotic diseases, pancreatitis, autoimmune disorders, diabetes, etc.)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 including but not limited to congenital / metabolic etiology, or with abnormal neuromuscular signs at screening or any screening CK
values suggestive of muscular disease, or age at which independent walking time first achieved after 16 months of age (based on birthday).
•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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Virus Diseases [C02]

compensated HBeAg-positive and negative chronic hepatitis B virus infection
MedDRA version: 19.0 Level: PT Classification code 10008910 Term: Chronic hepatitis B System Organ Class: 10021881 - Infections and infestations

Intervention(s)

Trade Name: Sebivo
Product Name: Sebivo
Product Code: LDT600
Pharmaceutical Form: Oral solution
INN or Proposed INN: TELBIVUDINE
CAS Number: 3424-98-4
Current Sponsor code: LDT600
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Oral solution
Route of administration of the placebo: Oral use

Trade Name: Sebivo
Product Name: Sebivo
Product Code: LDT600
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: TELBIVUDINE
CAS Number: 3424-98-4
Current Sponsor code: LDT600
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 600-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 24

Main Objective: 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 at Week 24.

Primary end point(s): The primary objective of the 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 at Week 24.

Secondary Objective: - Antiviral efficacy as evaluated by the proportion of patients achieving HBV DNA< 300 copies/mL at Week 52 and Week 104
- Biochemical response at Week 24, 52 and 104 as evaluated by proportion of patients whose baseline ALTs were abnormal and subsequently normalized
- Serological response at Week 24, 52 and 104 (HBeAg loss; HBeAg seroconversion and HBsAg loss and HBsAg seroconversion)
- Percentage of patients achieving composite endpoints at Week 52 and 104 (HBV DNA < 300 copies/mL, ALT normalization and HBeAg seroconversion)
- Cumulative rate of Virological Breakthrough at Week 52 and 104
- Presence of genotypic resistance in VB and non-responders patients at Week 24
- Safety assessments (SAEs, AEs, AESI (muscle related events), hepatic decompensation or HCC, chemistry or hematology abnormalities

Secondary Outcome(s)

Secondary end point(s): 1.anti-viral efficacy at Week52 and Week104
2. Biochemical response (ALT normalization) at Week 24, Week 52 and Week 104
3.Serological response at Week 24, Week 52 and Week 104
4. Composite endpoint (HBV DNA undetectability, ALT normalization and HBeAg seroconversion) at Week 52 and Week 104
5. Cumulative rate of Virological Breakthrough at Week 52 and 104
6. Presence of genotypic resistance in VB and non-responders patients at Week 24 ( or who discontinued before Week 24)
7. safety endpoints (SAEs, AEs, Grade 3-4 AEs and AEs related to study drug, AESI (muscle related events), hepatic decompensation or HCC, Grade 3-4 chemistry or hematology abnormalities

Timepoint(s) of evaluation of this end point: Weeks 24, 52, 104

Secondary ID(s)

2012-004942-14-GB

CLDT600A2306

Source(s) of Monetary Support

Novartis Pharma Services AG

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 24/07/2019
• Date Completed: 09/01/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-004942-14/results