Clinical trial NCT00423891: A Study of Entecavir in Pediatric Patients With Chronic Hepatitis B Virus (HBV)-Infection
Official title: Evaluation of the Pharmacokinetics, Safety, Tolerability and Efficacy of Entecavir (ETV) in Pediatric Subjects With Chronic Hepatitis B Virus (HBV) Infection Who Are HBeAg-Positive
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hepatitis B, Chronic
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2007-01-18
Enrollment: 64
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this clinical study is to determine the appropriate doses of entecavir to use in children and adolescents. Safety, tolerability and efficacy will also be studied


Eligibility criteria: Inclusion Criteria:

* 2-18 years of age
* Group A: Lamivudine naive (\<1 week of Lamivudine) and not within 24 weeks of screening; Group B: Lamivudine experienced (\> 12 weeks of Lamivudine); Group C: nucleoside/nucleotide experienced (\> 12 weeks of nucleoside/tide therapy) added as a country-specific protocol amendment (not all sites had Group C).
* HBV Deoxyribonucleic acid (DNA) ≥ 100000 copies/mL; ≥ 10000 copies for nucleoside/nucleotide experienced (Group C)
* Detectable Hepatitis B surface antigen (HBsAg) for 24 weeks prior to screening
* Hepatitis B e antigen (HBeAg) positive
* Compensated liver and renal function
* Elevated alanine aminotransferase (ALT) at screening and during the 24 weeks prior to screening (for Groups A and B)

Exclusion Criteria:

* Coinfection with Human immunodeficiency virus (HIV), Hepatitis C virus (HCV), Hepatitis D Virus (HDV)
* Children who were breastfed while their mother received Lamivudine, or children whose mothers received Lamivudine during pregnancy

Primary outcomes:
measure: Number of Participants With Serious Adverse Events (SAE) and Discontinuations Due to Adverse Events (AEs) - On Treatment
timeFrame: Day 1 to Week 120
Secondary outcomes:
measure: Mean Maximum Observed Plasma Concentration (Cmax) and Mean Trough Observed Plasma Concentration (Cmin) of Entecavir in LVD-naive and LVD-experienced Participants, by Age Cohort
timeFrame: Day 14
measure: Median Time of Maximum Observed Plasma Concentration (Tmax) in LVD-naive and LVD-experienced Participants, by Age Cohort
timeFrame: Day 14
measure: Mean Area Under the Concentration-Time Curve in One Dosing Interval [AUC(TAU)] of Entecavir in LVD-naive and LVD-experienced Participants, by Age Cohort
timeFrame: Day 14
measure: Mean Apparent Total Body Clearance (CLT/F) of Entecavir in LVD-naive and LVD-experienced Participants, by Age Cohort
timeFrame: At 2 weeks
measure: Number of Participants With HBV DNA Less Than 50 IU/mL Through Week 96 in Treated Participants
timeFrame: Baseline to Week 96
measure: Number of Participants With Hepatitis B e Antigen (HBeAg) Loss Through Week 96 in Treated Participants
timeFrame: Baseline to Week 96
measure: Number of Participants With Hepatitis B s Antigen (HBsAg) Loss Through Week 96 in Treated Participants
timeFrame: Baseline to Week 96
measure: Number of Participants With Hepatitis B e Antigen Seroconversion Through Week 96 in Treated Participants
timeFrame: Baseline through Week 96
measure: Number of Participants With HBV DNA Less Than Lower Limit of Detection (LLD) for the Roche COBAS TaqMan - HPS Assay at Week 96 in Treated Participants
timeFrame: Baseline to Week 96
measure: Number of Participants With HBV DNA Less Than Lower Limit of Quantification (LLQ) for the Roche COBAS TaqMan - HPS Assay Through Week 96 in Treated Participants
timeFrame: Baseline through Week 96
measure: Number of Participants With HB s Antigen (HBsAg) Seroconversion Through Week 96 in Treated Participants
timeFrame: Baseline through Week 96
measure: Number of Participants Who Had a Protocol Defined Response (PDR) Through Week 96 in Treated Participants
timeFrame: Baseline to Week 96
measure: Mean Log10 Change From Baseline in HBV DNA Using Roche COBAS TaqMan - HPS Through Week 96 in Treated Participants
timeFrame: Baseline to Week 96
measure: Alanine Aminotransferase (ALT) Normalization From Baseline Through Week 96 in Treated Participants
timeFrame: Baseline to Week 96
measure: Number of Participants With HBV DNA by PCR Categories at Weeks 48 and 96 in Treated Participants
timeFrame: Baseline, Week 48, Week 96
measure: Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL Through Week 96 in Treated Participants
timeFrame: Baseline to Week 96
measure: Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL, Plus HBeAg Seroconversion Through Week 96 in Treated Participants
timeFrame: Baseline to Week 96
measure: Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL, Without HBeAg Seroconversion, Through Week 96 in Treated Participants
timeFrame: Baseline to Week 96
measure: Number of Participants With Hematology Laboratory Abnormalities (Grades 1 - 4) - On Treatment - Treated Participants
timeFrame: Day 1 to Week 120
measure: Number of Participants With Chemistry Laboratory Abnormalities (Grades 1 - 4) - On Treatment - Treated Participants
timeFrame: Day 1 to Week 120
measure: Number of Participants With Electrolyte Laboratory Abnormalities (Grades 1 - 4) - On Treatment - Treated Participants
timeFrame: Day 1 Week 120
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Hartford
country: United States
facility: Connecticut Children'S Medical Center
state: Connecticut
city: Gainesville
country: United States
facility: University Of Florida
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins School Of Medicine
state: Maryland
city: Boston
country: United States
facility: Boston Childrens Hospital
state: Massachusetts
city: New York
country: United States
facility: Mount Sinai School Of Medicine
state: New York
city: Philadelphia
country: United States
facility: Children'S Hospital Of Philadelphia
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Dallas
country: United States
facility: University Of Texas Southwestern Medical Center
state: Texas
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Bruxelles
country: Belgium
facility: Local Institution
city: Porto Alegre
country: Brazil
facility: Local Institution
state: Rio Grande Do Sul
city: Sco Paulo
country: Brazil
facility: Local Institution
state: Sao Paulo
city: Toronto
country: Canada
facility: Local Institution
state: Ontario
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Taipei
country: Taiwan
facility: Local Institution
city: London
country: United Kingdom
facility: Local Institution
state: Greater London
city: Birmingham
country: United Kingdom
facility: Local Institution
state: West Midlands
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: