Clinical trial NCT00410072: Entecavir Plus Tenofovir Combination Therapy Versus Entecavir Monotherapy in Naive Subjects With Chronic Hepatitis B
Official title: A Comparative Study of Chronic Hepatitis B Subjects Treated With Entecavir Plus Tenofovir Combination Therapy vs. Entecavir Monotherapy in Adults Who Are Treatment-Naive to Nucleosides and Nucleotides: The BE-LOW Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis B, Chronic
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2006-12-12
Enrollment: 669
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the effectiveness of entecavir plus tenofovir combination therapy with that of entecavir monotherapy. Safety will also be studied.


Eligibility criteria: Inclusion Criteria:

* Chronic hepatitis B virus (HBV) infection (hepatitis B e antigen \[HbeAg\]-positive or negative) disease
* Nucleoside- and nucleotide-naive
* Males or females ≥16 years of age (or minimum age of consent in a given country)
* Compensated liver function
* HBV DNA \>1.72\*10\*5\*IU/mL (approximately 10\*6\*copies/mL) for HbeAg-positive participants
* HBV DNA \>1.72\*10\*4\*IU/mL (approximately 10\*5\*copies/mL) for Hbe-Ag-negative participants
* Alanine aminotransferase level ≥\*upper limit of normal (ULN) and ≤10\*ULN

Exclusion Criteria:

* Evidence of decompensated cirrhosis
* Coinfection with human immunodeficiency virus, hepatitis C virus, or hepatitis D virus
* Laboratory values out of protocol-specified range

Primary outcomes:
measure: Percentage of Participants Who Achieved Hepatitis B Virus DNA (HBV DNA) Levels <50 IU/mL by Polymerase Chain Reaction (PCR) at Week 96
timeFrame: At Week 96
Secondary outcomes:
measure: Percentage of Participants Who Achieved HBV DNA Levels <50 IU/mL by PCR at Week 48 and Week 96 by Hepatitis B e Antigen (HBeAg) Status
timeFrame: At Weeks 48 and 96
measure: Percentage of Participants Who Achieved HBV DNA Levels <LOQ by PCR at Weeks 48 and 96
timeFrame: At Weeks 48 and 96
measure: Percentage of Participants Who Achieved HBV DNA Levels <LOD by PCR at Weeks 48 and 96
timeFrame: At Weeks 48 and 96
measure: Mean Log 10 HBV DNA at Weeks 48 and 96
timeFrame: Baseline, Weeks 48 and 96
measure: Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 48 and 96
timeFrame: At Weeks 48 and 96
measure: Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 48 and 96
timeFrame: At Weeks 48 and 96
measure: Percentage of Participants With HBeAg Seroconversion [( at Weeks 48 and 96
timeFrame: At Weeks 48 and 96
measure: Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48 and 96
timeFrame: At Weeks 48 and 96
measure: Percentage of Participants With HBsAg Seroconversion at Weeks 48 and 96
timeFrame: At Weeks 48 and 96
measure: Number of Participants With HBV DNA in Relevant Categories at Weeks 48 and 96
timeFrame: At Weeks 48 and 96
measure: Number of Participants With Adverse Events, Serious Adverse Events, and Discontinuations From Study Drug Due to Adverse Events or Laboratory Abnormalities
timeFrame: From enrollment through Week 100 + 24-week follow-up
measure: Number of Participants With HBV Resistance Through Week 48
timeFrame: Week 48
measure: Number of Participants With HBV Resistance at Week 96
timeFrame: Week 96
measure: Number of Participants With Virologic Breakthrough at Week 48
timeFrame: Week 48
measure: Number of Participants With Virologic Breakthrough at Week 96
timeFrame: Week 96
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Sergio E. Rojter
state: California
city: San Diego
country: United States
facility: Tuan Nguyen, Md
state: California
city: San Jose
country: United States
facility: San Jose Gastroenterology
state: California
city: New Haven
country: United States
facility: Yale University School Of Medicine
state: Connecticut
city: Miami
country: United States
facility: University Of Miami
state: Florida
city: Atlanta
country: United States
facility: Atlanta Gastroenterology Associates
state: Georgia
city: Atlanta
country: United States
facility: Digestive Healthcare Of Georgia
state: Georgia
city: Baltimore
country: United States
facility: Digestive Disease Associates, P.A.
state: Maryland
city: Laurel
country: United States
facility: Maryland Digestive Disease Research, Llc
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University Of Michigan Health System
state: Michigan
city: Flushing
country: United States
facility: Sing Chan, Md
state: New York
city: Manhasset
country: United States
facility: North Shore University
state: New York
city: New York
country: United States
facility: Beth Israel Medical Center
state: New York
city: New York
country: United States
facility: Concorde Medical Group
state: New York
city: New York
country: United States
facility: Mount Sinai School Of Medicine
state: New York
city: Ciudad De Buenos Aires
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Ciudad De Buenos Aires
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Ciudad De Buenos Aires
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Rosario
country: Argentina
facility: Local Institution
state: Prov De Santa
city: Westmead Nsw
country: Australia
facility: Local Institution
state: New South Wales
city: Clayton Vic
country: Australia
facility: Local Institution
state: Victoria
city: Fitzroy
country: Australia
facility: Local Institution
state: Victoria
city: Heidelberg
country: Australia
facility: Local Institution
state: Victoria
city: Prahan
country: Australia
facility: Local Institution
state: Victoria
city: Belo Horizonte
country: Brazil
facility: Local Institution
state: Minas Gerais
city: Porto Alegre Rs
country: Brazil
facility: Local Institution
state: Rio Grande Do Sul
city: Calgary
country: Canada
facility: Local Institution
state: Alberta
city: Vancouver
country: Canada
facility: Local Institution
state: British Columbia
city: Winnipeg
country: Canada
facility: Local Institution
state: Manitoba
city: Toronto
country: Canada
facility: Local Institution
state: Ontario
city: Toronto
country: Canada
facility: Local Institution
state: Ontario
city: Toronto
country: Canada
facility: Local Institution
state: Ontario
city: Grenoble Cedex 09
country: France
facility: Local Institution
city: Marseille Cedex 08
country: France
facility: Local Institution
city: Paris Cedex 12
country: France
facility: Local Institution
city: Paris Cedex 13
country: France
facility: Local Institution
city: Paris
country: France
facility: Local Institution
city: Strasbourg
country: France
facility: Local Institution
city: Hyderabad
country: India
facility: Local Institution
state: Andhra Pradesh
city: Lucknow
country: India
facility: Local Institution
city: Ludhiana
country: India
facility: Local Institution
city: Vellore
country: India
facility: Local Institution
city: Antella Firenze
country: Italy
facility: Local Institution
city: Brescia
country: Italy
facility: Local Institution
city: Pisa
country: Italy
facility: Local Institution
city: Roma
country: Italy
facility: Local Institution
city: Durango
country: Mexico
facility: Local Institution
city: Bialystok
country: Poland
facility: Local Institution
city: Chorzow
country: Poland
facility: Local Institution
city: Krakow
country: Poland
facility: Local Institution
city: Lublin
country: Poland
facility: Local Institution
city: Warszawa
country: Poland
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Smolensk
country: Russian Federation
facility: Local Institution
city: St. Petersburg
country: Russian Federation
facility: Local Institution
city: St. Petersburg
country: Russian Federation
facility: Local Institution
city: St. Petersburg
country: Russian Federation
facility: Local Institution
city: St. Petersburg
country: Russian Federation
facility: Local Institution
city: Pretoria
country: South Africa
facility: Local Institution
state: Gauteng
city: Bellville
country: South Africa
facility: Local Institution
state: Western Cape
city: N1 City Goodwood
country: South Africa
facility: Local Institution
state: Western Cape
city: Bornova Izmir
country: Turkey
facility: Local Institution
city: Cebeci Ankara
country: Turkey
facility: Local Institution
city: Sihhiye Ankara
country: Turkey
facility: Local Institution
city: Trabzon
country: Turkey
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Lok AS, Trinh H, Carosi G, Akarca US, Gadano A, Habersetzer F, Sievert W, Wong D, Lovegren M, Cohen D, Llamoso C. Efficacy of entecavir with or without tenofovir disoproxil fumarate for nucleos(t)ide-naive patients with chronic hepatitis B. Gastroenterology. 2012 Sep;143(3):619-628.e1. doi: 10.1053/j.gastro.2012.05.037. Epub 2012 May 27.