A Phase III Study of the Safety and Efficacy of Entecavir in Pediatric Patients With Chronic Hepatitis B Virus Infection
- Conditions
- Chronic Hepatitis B Virus, Pediatric
- Interventions
- Drug: Placebo
- Registration Number
- NCT01079806
- Lead Sponsor
- Bristol-Myers Squibb
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 180
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Participants received placebo, 0 mg, once daily, for 48 to 96 weeks, depending on response Entecavir Entecavir Participants received entecavir, 0.015 mg/kg up to 0.5 mg, once daily, for 96 to 144 weeks, depending on response
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Achieved a Combination of Hepatitis B Virus (HBV) DNA Suppression and Hepatitis B e Antigen (HBeAg) Seroconversion at Week 48 At Week 48 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
Name Time Method Percentage of Participants Who Achieved Sustained HBeAg Seroconversion During Off-treatment Follow up Among Participants Who Achieved HBeAg Seroconversion at End of Dosing (EOD). Week 48, EOD (2 years) Participants who demonstrated HBeAg seroconversion at EOD were followed and assessed for presence of sustained HBeAg seroconversion during entire study. The study reached the end of dosing (EOD) on 22 Feb-2016.
Percentage of Participants With Serum Alanine Aminotransferase ≤1*Upper Limit of Normal at Week 48 At Week 48 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 Antigen (HBeAg) Seroconversion at Week 48 (Undetectable HBeAg and Presence of Anti-HBeAb) At Week 48 Percentage of participants in the primary cohort with HBeAg seroconversion (undetectable HBeAg and presence of anti-HBe antibodies) at week 48
Percentage of Participants With Hepatitis B Virus DNA <Limit of Quantitation (LOQ) at Week 48 At Week 48 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.
Histological Analysis (Percentage) Among Participants With Available Liver Biopsy Data Between weeks 48 and 96 Liver function test elevations and abnormalities on blinded and open-label ETV (the All ETV Safety Cohort). Participants who experienced elevation of alanine aminotransferase (ALT) greater than three times ETV (entecavir) baseline measure (Participants who displayed liver biopsy with ALT value greater than three times baseline.)
Percentage of Participants With Hepatitis B Virus (HBV) DNA <50 IU/mL at Week 48 At Week 48 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 Laboratory Test Results Meeting the Criteria for Abnormality (Grades 1-4) Day 1 through Week 48 on blinded therapy 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 Adverse Events (Including Palatability Issues), SAEs, Discontinuous Due to Adverse Events, and HBV Disease Progression Through Week 48 Day 1 through Week 48 on blinded therapy 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.
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 Day 1 through Week 96 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) (Continued) Day 1 through Week 48 on blinded therapy 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.
Percentage of Participants Who Maintained HBeAg Seroconversion at Week 96 (End of Blinded Therapy) Among Participants With HBeAg Seroconversion at Week 48 At Week 96 Participants who achieved HBeAg seroconversion by Week 48 and maintained seroconversion to week 96
Percentage of Participants With HBeAg Seroconversion on ETV Over-time at Week 96 (All ETV Cohort) At Week 96 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.
Percentage of Participants With HBeAg Seroconversion (Undetectable HBeAg and Presence of Anti-HBeAb) up to Week 96 up to week 96 On Treatment through week 96 - 2 year cohort NC = F: (The numerator was based on participants meeting the response criteria. The denominator was based on treated participants. Participants who had missing data at the analysis week were considered failures.)
Percentage of Participants With HbeAg Loss at Weeks 48 and 96 At 48 and 96 weeks HBeAg Loss (NC = F and NC = M) - On Treatment through Week 96 - Year 2 Efficacy Cohort Non-Completer - Failure (NC=F): The numerator was based on participants meeting the response criteria. The denominator was based on treated participants. Participants who had missing data at the analysis week were considered failures. Non-Completer - Missing (NC=M): The numerator was based on participants meeting the response criteria. The denominator was based on participants with data at the analysis week. Participants who had missing data at the analysis week were excluded.
Trial Locations
- Locations (16)
Children'S National Medical Center
🇺🇸Washington, District of Columbia, United States
Shah, Uzma
🇺🇸Boston, Massachusetts, United States
Children'S Hospital Of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Boston Childrens Hospital
🇺🇸Boston, Massachusetts, United States
Inova Fairfax Hospital For Children
🇺🇸Fairfax, Virginia, United States
University Of Florida
🇺🇸Gainesville, Florida, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
Texas Children'S Hospital
🇺🇸Houston, Texas, United States
Local Institution
🇬🇧Birmingham, West Midlands, United Kingdom
Romero, Rene
🇺🇸Atlanta, Georgia, United States
Connecticut Children'S Medical Center
🇺🇸Hartford, Connecticut, United States
Levine Children'S Hospital At Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
Johns Hopkins School Of Medicine
🇺🇸Baltimore, Maryland, United States
University Of California, San Francisco
🇺🇸San Francisco, California, United States
Indiana University School Of Medicine / Riley Hospital
🇺🇸Indianapolis, Indiana, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States