A Comparative Study of Chronic Hepatitis B Subjects Treated with Entecavir PlusTenofovir Combination Therapy vs Entecavir Monotherapy in Adults who are Treatment-Naïve to Nucleosides and Nucleotides: The BE-LOW Study.Revised Protocol 01, incorporating protocol amendment 02 (Version 2.0, Date 22-Jan-07). - The BE-LOW Study

Active, not recruiting

Conditions: CHRONIC HEPATITIS B VIRUS,TREATMENT-NAIV
MedDRA version: 8.1Level: LLTClassification code 10019743Term: Hepatitis B virus (HBV)

Registration Number: EUCTR2006-000421-62-GR

Lead Sponsor: Bristol-Myers Squibb International Corporation

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Not Recruiting

Sex: All

Target Recruitment: 462

Inclusion Criteria

1) Signed written informed consent
2) Nucleoside- and nucleotide-naïve subjects with chronic HBV infection (detectable
HBsAg at screening and for at least 24 weeks prior to screening, or detectable
HBsAg for < 24 weeks and negative for IgM core antibody);
3) Subjects must have compensated liver function and must meet ALL of the
following criteria:
• International Normalization Ratio (INR) =< 1.5
• Serum albumin >= 3 g/dL (>= 30 g/L)
• Serum total bilirubin =< 2.5 mg/dL (=< 42.75 µmol/L)
4) For HBeAg-positive subjects, HBV DNA >= 172,000 IU/mL (approximately 1,000,000 copies/mL) by PCR at screening; OR For HBeAg-negative subjects, HBV DNA >=17,200 IU/mL (approximately 100,000 copies/mL) by PCR at screening;
5) ALT >= 1.3 x the ULN at screening and at least once >= 12 weeks prior to screening;
6) Males and females >= 16 years of age (or minimum age of consent in a given
country)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1) 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;
2) WOCBP using a prohibited contraceptive method. At this time there are no
known contraindicated contraceptives to entecavir or tenofovir;
3) Women who are pregnant or breastfeeding;
4) Women with a positive pregnancy test on enrollment or prior to investigational
product administration;
5) Sexually active fertile men not using effective birth control if their partners are
WOCBP;
6) Evidence of decompensated cirrhosis including but not limited to: variceal
bleeding; hepatic encephalopathy; or ascites requiring management with diuretics
or paracentesis;
7) Coinfection with HIV, hepatitis C virus ([HCV]; coinfection is defined as HCV
Ab-positive with detectable HCV ribonucleic acid [RNA] by PCR), or hepatitis D
virus (HDV);
8) Recent history of pancreatitis (within 24 weeks prior to the first dose of study
medication);
9) Currently abusing illegal drugs or alcohol sufficient, in the Investigator’s opinion,
to prevent adequate compliance with study therapy or to increase the risk of
hepatotoxicity or pancreatitis;
10) Other serious medical conditions that might preclude completion of this study or
that require chronic administration of prohibited medications (see Exclusion
Criterion 19);
11) Serum creatinine > 1.5 mg/dL;
12) Hemoglobin < 10.0 g/dL;
13) Platelet count < 70,000/mm³;
14) Absolute neutrophil count < 1500 cells/mm³;
15) Serum alpha fetoprotein (AFP) level > 100 ng/mL;
• If the AFP level is between 21 and 100 ng/mL, it must be repeated prior to
randomization. If the repeat AFP level is between 21 and 100 ng/mL, and if
ultrasonography or computerized tomography (CT) of the liver performed
prior to the first dose of study medication does not demonstrate a focal lesion
suggestive of carcinoma, the subject may be dosed in the study;
16) Known history of allergy to nucleoside or nucleotide analogues;
17) Any prior therapy with nucleoside or nucleotide analogue antiviral agents with
activity against hepatitis B (e.g., adefovir, entecavir, famciclovir, tenofovir,
telbivudine, clevudine, emtracitabine), or any other experimental anti-HBV
antiviral;
18) Therapy with interferon; thymosin alpha or other immuno-stimulators within
24 weeks of randomization into this study;
19) Required chronic administration of medications which cause immunosuppression
or which are associated with a high risk of nephrotoxicity or hepatotoxicity or
which affect renal excretion (See Protocol Section 5.5.1 for examples);
20)Prisoners or subjects who are compulsorily detained (involuntarily incarcerated)
for treatment of either a psychiatric or physical (e.g., infectious disease) illness
must not be enrolled into this study;
21) Unable to tolerate oral medication;
22) Poor peripheral venous access.