NCT02058108

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

Terminated Phase 3 Results posted Last updated 10 September 2019

What this trial tests

Phase 3 trial testing Telbivudine in Chronic Hepatitis B in 53 participants. Terminated before completion.

Timeline

31 October 2014

Primary endpoint
9 January 2019

9 January 2019

Quick facts

Lead sponsor	Novartis Pharmaceuticals
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	53
Start date	31 October 2014
Primary completion	9 January 2019
Estimated completion	9 January 2019
Sites	29 locations across Greece, Ukraine, Israel, South Korea, Romania, Bulgaria, Turkey (Türkiye)

Drugs / interventions tested

• Telbivudine — full drug profile →
• Placebo

Conditions studied

• Chronic Hepatitis B — all drugs for Chronic Hepatitis B →

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

Adults 2 to 17, any sex, with Chronic Hepatitis B. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Patients Achieving Serum HBV DNA Level of <300 Copies/mL (51 IU/mL) at Week 24 Primary · 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.

Group	Value	95% CI
Telbivudine	5
Placebo	1

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

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 ter

Week 52

Group	Value	95% CI
Telbivudine	3
Placebo	0

Week 104

Group	Value	95% CI
Telbivudine	2

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

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

Group	Value	95% CI
Telbivudine	12
Placebo	0

Week 52

Group	Value	95% CI
Telbivudine	1
Placebo	1

Week 104

Group	Value	95% CI
Telbivudine	2

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

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 an

HBeAg loss at Week 24

Group	Value	95% CI
Telbivudine	1
Placebo	0

HBeAg seroconversion at Week 24

Group	Value	95% CI
Telbivudine	1
Placebo	0

HBeAg loss at Week 52

Group	Value	95% CI
Telbivudine	1
Placebo	0

HBeAg seroconversion at Week 52

Group	Value	95% CI
Telbivudine	1
Placebo	0

HBeAg loss at Week 104

Group	Value	95% CI
Telbivudine	1

HBeAg seroconversion at Week 104

Group	Value	95% CI
Telbivudine	1

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

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 an

HBsAg loss at Week 24

Group	Value	95% CI
Telbivudine	1
Placebo	0

HBsAg seroconversion at Week 24

Group	Value	95% CI
Telbivudine	0
Placebo	0

HBsAg loss at Week 52

Group	Value	95% CI
Telbivudine	0
Placebo	0

HBsAg seroconversion at Week 52

Group	Value	95% CI
Telbivudine	0
Placebo	0

HBsAg loss at Week 104

Group	Value	95% CI
Telbivudine	0

HBsAg seroconversion at Week 104

Group	Value	95% CI
Telbivudine	0

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 Secondary · Week 52, Week 104

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

Group	Value	95% CI
Telbivudine	1
Placebo	0

Week 104

Group	Value	95% CI
Telbivudine	1

Number of Patients Achieving Cumulative Rate of Virological Breakthrough (VB) at Week 52 and 104 Secondary · Week 52, Week 104

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

Group	Value	95% CI
Telbivudine	1
Placebo	0

Week 104

Group	Value	95% CI
Telbivudine	1
Placebo	0

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 Secondary · Week 24

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)

Cumulative virological breakthrough

Group	Value	95% CI
Telbivudine	0
Placebo	0

Cumulative treatment emergent genotypic resistance

Group	Value	95% CI
Telbivudine	1
Placebo	0

Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Death Secondary · From first dose of study treatment to 30 days after last dose of study treatment, up to 112 weeks

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.

On-treatment Adverse Event (AEs)

Group	Value	95% CI
Telbivudine	20
Placebo	4

On-treatment Serious Adverse Event (SAEs)

Group	Value	95% CI
Telbivudine	0
Placebo	0

On-treatment Deaths

Group	Value	95% CI
Telbivudine	0
Placebo	0

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 112 weeks.. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Initial LdT (Telbivudine)

Serious: 0/43 (0%)

Deaths: 0/43

Initial Placebo on Placebo Treatment

Serious: 0/10 (0%)

Deaths: 0/10

Initial Placebo on LdT Treatment After Switching

Serious: 0/5 (0%)

Deaths: 0/5

All Ldt

Serious: 0/48 (0%)

Deaths: 0/48

Other adverse events (25 terms — click to expand)

Reaction	System	Initial LdT (Telbivudine)	Initial Placebo on Placebo…	Initial Placebo on LdT Tre…	All Ldt
Headache	Nervous system disorders	—	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—	—
Viral upper respiratory tract infection	Infections and infestations	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—
Gastroenteritis	Infections and infestations	—	—	—	—
Blood creatine phosphokinase increased	Investigations	—	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Ear pain	Ear and labyrinth disorders	—	—	—	—
Conjunctival hyperaemia	Eye disorders	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—
Exanthema subitum	Infections and infestations	—	—	—	—
Laryngitis	Infections and infestations	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—
Otitis media	Infections and infestations	—	—	—	—
Pharyngitis	Infections and infestations	—	—	—	—
Tonsillitis	Infections and infestations	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—
Varicella	Infections and infestations	—	—	—	—
Viral infection	Infections and infestations	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Antibiotic prophylaxis	Surgical and medical procedures	—	—	—	—

Data from ClinicalTrials.gov NCT02058108 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Role of Virus-Related Chronic Inflammation and Mechanisms of Cancer Immune-Suppression in Pathogenesis and Progression of Hepatocellular Carcinoma.
   Borgia M, Dal Bo M, Toffoli G. · · 2021 · cited 32× · PMID 34503196 · DOI 10.3390/cancers13174387