Clinical trial NCT01079806: A Phase III Study of the Safety and Efficacy of Entecavir in Pediatric Patients With Chronic Hepatitis B Virus Infection
Official title: A Comparative Study of the Antiviral Efficacy and Safety of Entecavir (ETV) Versus Placebo in Pediatric Subjects With Chronic Hepatitis B Virus (HBV) Infection Who Are HBeAg-Positive
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Hepatitis B Virus, Pediatric
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2010-03-03
Enrollment: 180
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 this study was to evaluate the safety and efficacy of entecavir in pediatric patients with chronic hepatitis B virus infection


Eligibility criteria: Key Inclusion Criteria

* Males and females, aged 2 to \<18 years
* Hepatitis B surface antigen-positive
* Detectable hepatitis B e (HBe) antigen, and no detectable anti-HBe antibodies
* Alanine aminotransferase (ALT) 1.5 to \<10 times the upper limit of normal at screening and within 8 to 24 weeks prior to screening
* Evidence of the presence of hepatitis B virus DNA at least 4 weeks before screening and \>100,000 copies/mL at screening

Key Exclusion Criteria

* Any prior therapy with entecavir
* At least 12 weeks of prior therapy with any nucleoside or nucleotide antiviral agent
* Therapy with interferon alpha, thymosin alpha, or nucleototide antiviral agents within 24 weeks of screening
* Coinfection with HIV, hepatitis C virus, or hepatitis D virus
* Decompensated liver disease
* Liver transplant recipients
* Other forms of acute and chronic conditions which may cause increased ALT levels
* Children who were breastfed while their mothers received lamivudine or whose mothers received lamivudine during pregnancy

Primary outcomes:
measure: Percentage of Participants Who Achieved a Combination of Hepatitis B Virus (HBV) DNA Suppression and Hepatitis B e Antigen (HBeAg) Seroconversion at Week 48
timeFrame: At Week 48
Secondary outcomes:
measure: Percentage of Participants With Hepatitis B Virus (HBV) DNA <50 IU/mL at Week 48
timeFrame: At Week 48
measure: Percentage of Participants With Serum Alanine Aminotransferase ≤1*Upper Limit of Normal at Week 48
timeFrame: At Week 48
measure: Percentage of Participants With Hepatitis B Virus DNA <Limit of Quantitation (LOQ) at Week 48
timeFrame: At Week 48
measure: Percentage of Participants With Hepatitis B e Antigen (HBeAg) Seroconversion at Week 48 (Undetectable HBeAg and Presence of Anti-HBeAb)
timeFrame: At Week 48
measure: Percentage of Participants Who Achieved Sustained HBeAg Seroconversion During Off-treatment Follow up Among Participants Who Achieved HBeAg Seroconversion at End of Dosing (EOD).
timeFrame: Week 48, EOD (2 years)
measure: Number of Participants With Adverse Events (Including Palatability Issues), SAEs, Discontinuous Due to Adverse Events, and HBV Disease Progression Through Week 48
timeFrame: Day 1 through Week 48 on blinded therapy
measure: Number of Participants With Laboratory Test Results Meeting the Criteria for Abnormality (Grades 1-4)
timeFrame: Day 1 through Week 48 on blinded therapy
measure: Number of Participants With Laboratory Test Results Meeting the Criteria for Abnormality (Grades 1-4) (Continued)
timeFrame: Day 1 through Week 48 on blinded therapy
measure: Percentage of Participants With HBeAg Seroconversion on ETV Over-time at Week 96 (All ETV Cohort)
timeFrame: At Week 96
measure: Percentage of Participants Who Maintained HBeAg Seroconversion at Week 96 (End of Blinded Therapy) Among Participants With HBeAg Seroconversion at Week 48
timeFrame: At Week 96
measure: Percentage of Participants With Death as Outcome, Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Related AEs, Grade 2-4 Related AEs, Grade 3-4 AEs, Malignancies, ALT Flares, and Hepatic Disease Progression Through Week 96
timeFrame: Day 1 through Week 96
measure: Percentage of Participants With HBeAg Seroconversion (Undetectable HBeAg and Presence of Anti-HBeAb) up to Week 96
timeFrame: up to week 96
measure: Histological Analysis (Percentage) Among Participants With Available Liver Biopsy Data
timeFrame: Between weeks 48 and 96
measure: Percentage of Participants With HbeAg Loss at Weeks 48 and 96
timeFrame: At 48 and 96 weeks
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: Washington
country: United States
facility: Children'S National Medical Center
state: District of Columbia
city: Gainesville
country: United States
facility: University Of Florida
state: Florida
city: Atlanta
country: United States
facility: Romero, Rene
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University School Of Medicine / Riley Hospital
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins School Of Medicine
state: Maryland
city: Boston
country: United States
facility: Shah, Uzma
state: Massachusetts
city: Boston
country: United States
facility: Boston Childrens Hospital
state: Massachusetts
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Charlotte
country: United States
facility: Levine Children'S Hospital At Carolinas Medical Center
state: North Carolina
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: Houston
country: United States
facility: Texas Children'S Hospital
state: Texas
city: Fairfax
country: United States
facility: Inova Fairfax Hospital For Children
state: Virginia
city: Bunos Aires
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Bruxelles
country: Belgium
facility: Local Institution
city: Toronto
country: Canada
facility: Local Institution
state: Ontario
city: Mainz
country: Germany
facility: Local Institution
state: Rheinland Pfalz
city: Starnberg
country: Germany
facility: Local Institution
city: Wuppertal
country: Germany
facility: Local Institution
city: Thesaloniki
country: Greece
facility: Local Institution
city: Guwahati
country: India
facility: Local Institution
city: Hyderabad
country: India
facility: Local Institution
city: Beer-sheva
country: Israel
facility: Local Institution
city: Petach Tikva
country: Israel
facility: Local Institution
city: Zefat
country: Israel
facility: Local Institution
city: Daegu
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Bydgoszcz
country: Poland
facility: Local Institution
city: Krakow
country: Poland
facility: Local Institution
city: Wroclaw
country: Poland
facility: Local Institution
city: Bucharest
country: Romania
facility: Local Institution
city: Iasi
country: Romania
facility: Local Institution
city: Timisoara
country: Romania
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Novokuznetsk
country: Russian Federation
facility: Local Institution
city: St. Petersburg
country: Russian Federation
facility: Local Institution
city: Tainan
country: Taiwan
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:
citation: Jonas MM, Chang MH, Sokal E, Schwarz KB, Kelly D, Kim KM, Ling SC, Rosenthal P, Oraseanu D, Reynolds L, Thiry A, Ackerman P. Randomized, controlled trial of entecavir versus placebo in children with hepatitis B envelope antigen-positive chronic hepatitis B. Hepatology. 2016 Feb;63(2):377-87. doi: 10.1002/hep.28015. Epub 2015 Oct 16.