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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: September 25, 2014
Last verified: September 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: 180
Study Start Date: June 2010
Estimated Study Completion Date: March 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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01079806

  Hide Study Locations
Locations
United States, California
University Of California, San Francisco
San Francisco, California, United States, 94143
United States, Connecticut
Connecticut Children'S Medical Center
Hartford, Connecticut, United States, 06106
United States, District of Columbia
Children'S National Medical Center
Washington, District of Columbia, United States, 20010
United States, Florida
University Of Florida
Gainesville, Florida, United States, 32610
United States, Georgia
Romero, Rene
Atlanta, Georgia, United States, 30322
United States, Indiana
Indiana University School Of Medicine / Riley Hospital
Indianapolis, Indiana, United States, 46202
United States, Maryland
Johns Hopkins School Of Medicine
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Boston Childrens Hospital
Boston, Massachusetts, United States, 02115
Shah, Uzma
Boston, Massachusetts, United States, 02114
United States, New York
Mount Sinai Medical Center
New York, New York, United States, 10029
United States, North Carolina
Levine Children'S Hospital At Carolinas Medical Center
Charlotte, North Carolina, United States, 28203
United States, Pennsylvania
Children'S Hospital Of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States, 02903
United States, Texas
Texas Children'S Hospital
Houston, Texas, United States, 77030
United States, Virginia
Inova Fairfax Hospital For Children
Fairfax, Virginia, United States, 22031
Argentina
Local Institution
Bunos Aires, Buenos Aires, Argentina, 1425
Belgium
Local Institution
Bruxelles, Belgium, 1200
Canada, Ontario
Local Institution
Toronto, Ontario, Canada, M5G 1X8
Germany
Local Institution
Mainz, Rheinland Pfalz, Germany, 55131
Local Institution
Starnberg, Germany, 82319
Local Institution
Wuppertal, Germany, 42283
Greece
Local Institution
Thesaloniki, Greece, 54635
India
Local Institution
Guwahati, India, 781006
Local Institution
Hyderabad, India, 500029
Israel
Local Institution
Beer-sheva, Israel, 84101
Local Institution
Petach Tikva, Israel
Local Institution
Zefat, Israel, 13110
Korea, Republic of
Local Institution
Daegu, Korea, Republic of, 700-721
Local Institution
Seoul, Korea, Republic of, 138-736
Local Institution
Seoul, Korea, Republic of, 135-710
Poland
Local Institution
Bydgoszcz, Poland, 85-030
Local Institution
Krakow, Poland, 31-202
Local Institution
Wroclaw, Poland, 50-345
Romania
Local Institution
Bucharest, Romania, 011743
Local Institution
Iasi, Romania, 700309
Local Institution
Timisoara, Romania, 300011
Russian Federation
Local Institution
Moscow, Russian Federation, 111123
Local Institution
Moscow, Russian Federation, 117198
Local Institution
Novokuznetsk, Russian Federation, 654063
Local Institution
St. Petersburg, Russian Federation, 197022
Taiwan
Local Institution
Tainan, Taiwan, 704
Local Institution
Taipei, Taiwan, 100
United Kingdom
Local Institution
London, Greater London, United Kingdom, SE5 9RS
Local Institution
Birmingham, West Midlands, United Kingdom, B4 6NH
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: September 25, 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 B, Chronic
Hepatitis, Chronic
DNA Virus Infections
Digestive System Diseases
Enterovirus Infections
Hepadnaviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Entecavir
Anti-Infective Agents
Antiviral Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014