A Phase III Study of the Safety and Efficacy of Entecavir in Pediatric Patients With Chronic Hepatitis B Virus Infection

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01079806
First received: March 2, 2010
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

The purpose of this study was to evaluate the safety and efficacy of entecavir in pediatric patients with chronic hepatitis B virus infection


Condition Intervention Phase
Chronic Hepatitis B Virus, Pediatric
Drug: Entecavir
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Percentage of Participants Who Achieved a Combination of Hepatitis B Virus (HBV) DNA Suppression and Hepatitis B e Antigen (HBeAg) Seroconversion at Week 48 [ Time Frame: At Week 48 ] [ Designated as safety issue: No ]
    Suppression=HBV DNA<50 IU/mL (approximately 300 copies/mL) using the Roche COBAS TaqMan HBV Test for use with the High Pure System assay; seroconversion=undetectable HBeAg and detectable anti-hepatitis B e antibodies. While the analysis of the primary endpoint was based on a randomized sample size of 123 participants (the Primary Cohort), the size of the overall study population was augmented to 180 randomized participants to meet global regulatory requirements.


Secondary Outcome Measures:
  • Percentage of Participants With Hepatitis B Virus (HBV) DNA <50 IU/mL at Week 48 [ Time Frame: At Week 48 ] [ Designated as safety issue: No ]
    While the analysis of the primary endpoint was based on a randomized sample size of 123 participants (the Primary Cohort), the size of the overall study population was augmented to 180 randomized participants to meet global regulatory requirements.

  • Percentage of Participants With Hepatitis B Virus DNA <Limit of Quantitation (LOQ) at Week 48 [ Time Frame: At Week 48 ] [ Designated as safety issue: No ]
    LOQ=29 IU/mL. While the analysis of the primary endpoint was based on a randomized sample size of 123 participants (the Primary Cohort), the size of the overall study population was augmented to 180 randomized participants to meet global regulatory requirements.

  • Percentage of Participants With Serum Alanine Aminotransferase ≤1*Upper Limit of Normal at Week 48 [ Time Frame: At Week 48 ] [ Designated as safety issue: No ]
    While the analysis of the primary endpoint was based on a randomized sample size of 123 participants (the Primary Cohort), the size of the overall study population was augmented to 180 randomized participants to meet global regulatory requirements.

  • Percentage of Participants With Hepatitis B e (HBe) Seroconversion at Week 48 [ Time Frame: At Week 48 ] [ Designated as safety issue: No ]
    HBe seroconversion=undetectable HBe antigen and detectable anti-HBe antibodies. While the analysis of the primary endpoint was based on a randomized sample size of 123 participants (the Primary Cohort), the size of the overall study population was augmented to 180 randomized participants to meet global regulatory requirements.

  • Number 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 [ Time Frame: Day 1 through Week 48 on blinded therapy ] [ Designated as safety issue: Yes ]
    AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=having certain, probable, possible, or unknown relationship to study drug. Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death. ALT=alanine aminotransferase.

  • Number of Participants With Laboratory Test Results Meeting the Criteria for Abnormality (Grades 1-4) [ Time Frame: Day 1 through Week 48 on blinded therapy ] [ Designated as safety issue: Yes ]
    Toxicities graded per Division of AIDS criteria, Version 1.0, and modified World Health Organization criteria. INR=international normalization ratio of prothrombin time; ULN=upper limit of normal. Hemoglobin (g/dL): Grade 1=10-10.9; Grade 2=9-9.9; Grade 3=7-8.9; Grade 4= <7. Platelets (/mm^3): Grade 1=100,000-124,999; Grade 2=50,000-99,999; Grade 3=25,000-49,999; Grade 4= <25,000. INR (*ULN): Grade 1=1.1-1.5; Grade 2=1.6-2; Grade 3=2.1-3; Grade 4= >3. WBC (/mm^3): Grade 1=2000-2500; Grade 2=1500-1999; Grade 3=1000-1499; Grade 4= <1000. Neutrophils (/mm^3): Grade 1=1000-1300; Grade 2=750-999; Grade 3=500-749; Grade 4= <500.

  • Number of Participants With Laboratory Test Results Meeting the Criteria for Abnormality (Grades 1-4) (Continued) [ Time Frame: Day 1 through Week 48 on blinded therapy ] [ Designated as safety issue: Yes ]
    Toxicities graded per Division of AIDS criteria, Version 1.0, and modified World Health Organization criteria. ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea nitrogen; ULN=upper limit of normal; LLN=lower limit of normal. ALT, AST (*ULN): Grade 1=1.25-2; Grade 2=2.6-5; Grade 3=5.1-10; Grade 4= >10. Bilirubin (*ULN): Grade 1=1.1-1.5; Grade 2=1.6-2.5; Grade 3=2.6-5; Grade 4= >5. Albumin (g/dL): Grade 1=3- <LLN; Grade 2=2-2.9; Grade 3= <2. Lipase (*ULN): Grade 1=1.1-1.5; Grade 2=1.6-3; Grade 3=3.1-5; Grade 4= >5. BUN/urea (*ULN): Grade 1=1.25-<2.6; Grade 2=2.6-<5.1; Grade 3=5.1-10; Grade 4= >10. Chloride, high (mEq/L): Grade 1=113-<117; Grade 2=117-<121; Grade 3=121-125; Grade 4= >125. Potassium, low (mEq/L): Grade 1=3-3.4; Grade 2=2.5-<3; Grade 3=2-<2.5; Grade 4=<2. Potassium, high (mEq/L): : Grade 1= 5.6-<6.1; Grade 2=6.1-<6.6; Grade 3=6.6-7; Grade 4= >7. Sodium, high (mEq/L): Grade 1=146<151; Grade 2=151-<155; Grade 3=155-<160; Grade 4= >=160.


Enrollment: 228
Study Start Date: July 2010
Estimated Study Completion Date: April 2018
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Entecavir
Participants received entecavir, 0.015 mg/kg up to 0.5 mg, once daily, for 96 to 144 weeks, depending on response
Drug: Entecavir
Tablets/oral solution, 0.015 mg/kg up to 0.5 mg, administered orally, once daily, for 96 to144 weeks, depending on response
Other Names:
  • Baraclude
  • BMS-200475
Placebo Comparator: Placebo
Participants received placebo, 0 mg, once daily, for 48 to 96 weeks, depending on response
Drug: Placebo
Tablets/oral solution, 0 mg, administered orally, once daily, for 48 to 96 weeks, depending on response

  Eligibility

Ages Eligible for Study:   2 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 nucletotide 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01079806

  Show 43 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01079806     History of Changes
Other Study ID Numbers: AI463-189 ST
Study First Received: March 2, 2010
Results First Received: March 17, 2014
Last Updated: March 17, 2014
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
Brazil: ANVIA, CONEP
Canada: Health Canada
Greece: Ethics Committee
Greece: National Organization of Medicines
Germany: Federal Institute for Drugs and Medical Devices
Germany: Paul-Ehrlich-Institut
India: Central Drugs Standard Control Organization
India: Indian Council of Medical Research
Israel: Israeli Health Ministry Pharmaceutical Administration
Korea: Food and Drug Administration
Poland: National Institute of Medicines
Poland: Ministry of Science and Higher Education
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicines Agency
Russia: FSI Scientific Center of Expertise of Medical Application
Taiwan: Department of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
Virus Diseases
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Entecavir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 21, 2014