Health Condition 1: null- Pediatric Subjects ( 12 to 18 yrs ) with Chronic Hepatitis B Virus (HBV) Infection who are HBeAg-Positive
Conditions
Interventions
Intervention1: entecavir (BMS-200475) 0.5 mg tablets or Oral Solution: Entecavir : Tablets or Oral Solution, Oral, 0.015 mg/kg up to 0.5 mg, once daily, 96-144 weeks, depending on response
Placebo : T
Sponsors
The pharmaceutical company sponsoring this study is BristolMyers Squibb
Eligibility
Inclusion criteria
Inclusion criteria: Inclusion Criteria 1) Signed Written Informed Consent a) Freely given informed consent must be obtained prior to clinical trial participation, including informed consent for any screening procedures conducted to establish subject eligibility for the trial. Minor?s parents or legally acceptable representatives must give fully informed written consent. Assent should be obtained when the minor is judged to be of an age of reason (see Appendix 1); 2) Target Population a) History of CHB infection defined as HBsAg-positive at the Screening visit and on at least one other occasion ≥ 24 weeks prior to screening; b) Detectable HBeAg AND no detectable anti-HBe antibodies at screening and at least once ≥ 4 weeks prior to screening; c) Serum ALT 1.5 to within 8 to 24 weeks prior to screening; d) HBV DNA by PCR ≥ 105 copies/mL at screening and evidence of the presence of HBV DNA at least once ≥ 4 weeks prior to screening; 3) Age and Sex a) Male and females, 2 to Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 6 weeks after the last dose of investigational product in such a manner that the risk of pregnancy is minimized. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal. Post menopause is defined as: ? Amenorrhea ≥ 12 consecutive months without another cause or ? For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) at screening AND within 72 hours prior to the start of investigational product.
Exclusion criteria
Exclusion criteria: Sex and Reproductive Status a) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 6 weeks after the last dose of investigational product b) WOCBP using a prohibited contraceptive method. At this time there are no known contraindicated contraceptives to entecavir c) Women who are pregnant or breastfeeding d) Women with a positive pregnancy test on enrollment or prior to investigational product administration e) Sexually active fertile men not using effective birth control if their partners are WOCBP Target Disease Exceptions a) Co-infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis D virus (HDV) b) Other forms of acute and chronic conditions which may cause increased ALT as determined by the investigators (eg, acute viral illness, Wilson Disease, other metabolic disorders, autoimmune hepatitis, alcoholic liver disease) c) Liver transplant recipients Medical History and Concurrent Diseases a) Current evidence of, or history of variceal bleeding, hepatic encephalopathy, or ascites requiring diuretics or paracentesis or evidence of these on physical examination performed for this study; b) Current evidence of, or history of pancreatitis c) Received bone marrow or organ transplant or therapy with an immunomodulatory, cytotoxic, or systemic corticosteroid therapies within 2 months of enrollment d)Evidence of current pre-malignant lesions and malignancies including HCC(to be excluded by screening and evaluation practices standard in the country of enrollment) e)Other serious medical conditions that might preclude completion of this study 4) Physical and Laboratory Test Findings a) Hemoglobin 10.0 g/dL b) Platelet count 70,000/mm3 c) Inadequate renal function with estimated glomerular filtration rate of 50 mL/min/1.73m2 d) Total serum bilirubin 2.5 mg/dL ( 42.75 ¦Ìmol/L) e) INR 1.5 f) Serum albumin 3.0 g/dL ( 30 g/L) g) Alpha Fetoprotein ¡Ý 50 ng/mL 5) Allergies and Adverse Drug Reactions a) Known allergy to nucleoside analogues 6) Prohibited Treatments and/or Therapies a) ¡Ý 12 weeks of prior therapy with any nucleoside or nucleotide antiviral agent with activity against hepatitis B virus (including but not limited to adefovir, tenofovir famciclovir, clevudine, lamivudine, telbivudine, or emtricitabine) b) Therapy with interferon alpha, thymosin alpha or any nucleos[t]ide antiviral agent with activity against hepatitis B virus within 24 weeks of screening c) Any prior therapy with ETV; d) Any use of illegal drugs OR use of alcoholic beverages which in the investigator¡¯s opinion is sufficient to prevent adequate compliance with study procedures or increase the risk pancreatitis or hepatotoxicty; e) Concomitant medications which may cause immunosuppression, nephrotoxicity or hepatotoxicity or affect renal excretion or hepatic metabolism are not permitted f) Concomitant use of Traditional Chinese Medicines or other herbal products purported to have antiviral activity or intended for use in improving/protecting liver function g) During the treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To compare the proportion of subjects in each treatment group who achieve a combination of HBV DNA suppression and HBeAg seroconversion (undetectable HBeAg AND detectable anti-HBe antibodies) at Week 48.Timepoint: To compare the proportion of subjects in each treatment group who achieve a combination of HBV DNA suppression and HBeAg seroconversion (undetectable HBeAg AND detectable anti-HBe antibodies) at Week 48. | — |
Secondary
| Measure | Time frame |
|---|---|
| Assess the serologic response rates (defined as HBsAg loss and/or seroconversion; and HBeAg loss and/or seroconversion) including durability of response off treatment; â?¢ Assess the virological response rates; â?¢ Assess the biochemical response rates; â?¢ Assess ETV resistance rates; â?¢ Evaluate the long-term safety of ETV use in pediatric patients.Timepoint: Week 48 | — |
Countries
Argentina, Belgium, Brazil, Canada, Democratic People's Republic of Korea, Germany, Greece, India, Israel, Poland, Romania, Russian Federation, Taiwan, United Kingdom, United States of America
Contacts
Public ContactSubashri Shivkumar
Bristol Myers Squibb India Pvt. Ltd.
Outcome results
None listed