Trial record 1 of 2 for:
entecavir and chronic hepatitis B and pediatric subjects
A Phase III Study of the Safety and Efficacy of Entecavir in Pediatric Patients With Chronic Hepatitis B Virus Infection
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT01079806 |
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Recruitment Status :
Completed
First Posted : March 3, 2010
Results First Posted : April 21, 2014
Last Update Posted : May 9, 2019
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Sponsor:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Bristol-Myers Squibb
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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
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Chronic Hepatitis B Virus, Pediatric | Drug: Entecavir Drug: Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 180 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, 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 |
| Actual Study Start Date : | June 30, 2010 |
| Actual Primary Completion Date : | March 31, 2013 |
| Actual Study Completion Date : | March 31, 2018 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Entecavir
| Arm | Intervention/treatment |
|---|---|
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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
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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:
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Placebo Comparator: Placebo
Participants received placebo, 0 mg, once daily, for 48 to 96 weeks, depending on response
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Drug: Placebo
Tablets/oral solution, 0 mg, administered orally, once daily, for 48 to 96 weeks, depending on response |
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 ]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 ]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 ]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 ]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 Hepatitis B e Antigen (HBeAg) Seroconversion at Week 48 (Undetectable HBeAg and Presence of Anti-HBeAb) [ Time Frame: 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 Who Achieved Sustained HBeAg Seroconversion During Off-treatment Follow up Among Participants Who Achieved HBeAg Seroconversion at End of Dosing (EOD). [ Time Frame: 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.
- Number of Participants With Adverse Events (Including Palatability Issues), SAEs, Discontinuous Due to Adverse Events, and HBV Disease Progression Through Week 48 [ Time Frame: 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.
- 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 ]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 ]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 With HBeAg Seroconversion on ETV Over-time at Week 96 (All ETV Cohort) [ Time Frame: 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 Who Maintained HBeAg Seroconversion at Week 96 (End of Blinded Therapy) Among Participants With HBeAg Seroconversion at Week 48 [ Time Frame: At Week 96 ]Participants who achieved HBeAg seroconversion by Week 48 and maintained seroconversion to week 96
- 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 [ Time Frame: 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.
- Percentage of Participants With HBeAg Seroconversion (Undetectable HBeAg and Presence of Anti-HBeAb) up to Week 96 [ Time Frame: 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.)
- Histological Analysis (Percentage) Among Participants With Available Liver Biopsy Data [ Time Frame: 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 HbeAg Loss at Weeks 48 and 96 [ Time Frame: 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.
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| Ages Eligible for Study: | 2 Years to 17 Years (Child) |
| Sexes Eligible for Study: | All |
| 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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01079806
Locations
Show 44 study locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
Study Documents (Full-Text)
Documents provided by Bristol-Myers Squibb:
Documents provided by Bristol-Myers Squibb:
Statistical Analysis Plan [PDF] December 5, 2016
Study Protocol [PDF] September 4, 2012
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Bristol-Myers Squibb |
| ClinicalTrials.gov Identifier: | NCT01079806 |
| Other Study ID Numbers: |
AI463-189 ST |
| First Posted: | March 3, 2010 Key Record Dates |
| Results First Posted: | April 21, 2014 |
| Last Update Posted: | May 9, 2019 |
| Last Verified: | April 2019 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Hepatitis A Hepatitis B Hepatitis B, Chronic Hepatitis Hepatitis, Chronic Hepatitis, Viral, Human Entecavir Infections Liver Diseases Digestive System Diseases |
Virus Diseases Enterovirus Infections Picornaviridae Infections RNA Virus Infections Blood-Borne Infections Communicable Diseases Hepadnaviridae Infections DNA Virus Infections Antiviral Agents Anti-Infective Agents |