Effect of Entecavir in Blacks/African Americans and Hispanics With Chronic Hepatitis B Virus (HBV) Infection

Phase 4

Completed

Conditions: Hepatitis B Infection

Interventions: Drug: Entecavir

Registration Number: NCT00371150

Lead Sponsor: Bristol-Myers Squibb

Brief Summary: The purpose of this clinical research study is to develop observational clinical experience with the use of entecavir in participants who are either of Black/African-American race or of Hispanic ethnicity.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 131

Inclusion Criteria

Chronic HBV infection, with either HBeAg-positive (HBeAb-negative) or HBeAg-negative (HBeAb-positive) disease
Black/African American Race and/or Hispanic ethnicity
Nucleoside/tide-naive
Males or females ≥ 16 years of age (or minimum age required in a given country)
Compensated liver function
ALT of 1.3 to 10 x upper limit of normal (ULN)
No Co-infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis D virus (HDV)

Exclusion Criteria

Women of childbearing potential (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 study medication has been discontinued
Women who are pregnant or breastfeeding
Women with a positive pregnancy test on enrollment or prior to study drug administration
Evidence of decompensated cirrhosis including but not limited to: variceal bleeding; hepatic encephalopathy; or ascites requiring management with diuretics or paracentesis
Recent history of pancreatitis (resolution of any recent pancreatitis must be documented by normal lipase at least 12 weeks prior to the first dose of study medication)
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
Other serious medical conditions that might preclude completion of this study or that require chronic administration of prohibited medications
Serum creatinine > 1.5 mg/dL
Hemoglobin < 10.0 g/dL
Platelet count < 70,000/mm3
Absolute neutrophil count < 1200 cells/mm3
Serum alpha fetoprotein (AFP) level > 100 ng/mL. If the AFP level is between 21 and 100 ng/mL, it must be repeated. 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
Known history of allergy to nucleoside analogues
Any prior therapy with Entecavir
Any prior or concomitant use of nucleoside or nucleotide analogue antiviral agents with activity against hepatitis B (e.g., ETV, lamivudine (LVD), tenofovir [TDF], emtricitabine (FTC), clevudine, telbivudine [LdT], famciclovir), or any other experimental anti-HBV antiviral agent
Therapy with interferon, thymosin alpha or other immunostimulators within 24 weeks of enrollment (i.e., dosing) into this study
Subjects who require chronic administration of concomitant medications which cause immunosuppression or which are associated with a high rate of nephrotoxicity or hepatotoxicity, or which affect renal excretion, should not be enrolled in this study
Unable to tolerate oral medication
Poor peripheral venous access
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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm1	Entecavir	-

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With HBV Deoxyribonucleic Acid (DNA) < 50 IU/mL by Polymerase Chain Reaction (PCR) at Week 48	Week 48 of ETV treatment	HBV DNA assessments were performed using the Roche COBAS® TaqMan AmpliPrep assay. HBV DNA \< 50 IU/mL = approximately \<300 copies/mL.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieve HBV DNA < Lower Limit of Quantitation (LOQ = 29 IU/mL [Approximately 169 Copies/mL]) at Week 48	Week 48	HBV DNA assessments were performed using the Roche COBAS® TaqMan AmpliPrep assay. LOQ is the level above which quantitative results may be obtained with a specified degree of confidence. The LOQ is mathematically defined as equal to 10 times the standard deviation of the results for a series of replicates used to determine a justifiable limit of detection.
Percentage of Participants With HBV DNA by PCR Category at Week 48	Week 48	HBV DNA assessments were performed using the Roche COBAS® TaqMan AmpliPrep assay.
Percentage of Participants With Virologic Rebound Through Week 48 While on Continued Dosing With ETV	through Week 48	Virologic rebound is defined as a confirmed increase of ≥ 1 log10 in HBV DNA from the participant's nadir value (2 sequential HBV DNA measurements or last on-treatment measurement)
Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48	Week 48	ALT normalization=ALT level being less than or equal to 1 times the upper limit of normal (ULN). ULN for ALT is 37 U/L.
Percentage of Participants With Confirmed HBeAg Loss at Week 48 (for HBeAg-positive Participants Only)	Week 48	HBeAg is a hepatitis B viral protein. HBeAg loss = HBeAg-negative at the specified analysis week
Percentage of Participants With HBeAg Seroconversion at Week 48 (for HBeAg-positive Participants Only)	Week 48	HBeAg is a hepatitis B viral protein. HBeAg Seroconversion = HBeAg Loss and Presence of Hepatitis B e Antibody (HBeAb).
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48	Week 48	HBsAg = a part of the hepatitis B virus that, when in the blood, is a marker of infection. HBsAg loss = HBsAg-negative at the specified analysis week.
Percentage of Participants With HBsAg Seroconversion at Week 48	Week 48	HBsAg = a part of the hepatitis B virus that, when in the blood, is a of infection. HBs seroconversion is defined as HBsAg loss with positive HBsAb.
Mean log10 Reduction From Baseline in HBV DNA at Week 48	baseline, Week 48	HBV DNA was analyzed by PCR, using the Roche COBAS®TaqMan TaqMan AmpliPrep assay. Reduction in log10 HBV count=reduced viral load.
Percentage of Participants With HBV DNA < Other IU Cut-off Points That May be Clinically Relevant at the Time of Data Analysis	Week 48
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations From Study Drug Due to Adverse Events	From enrollment through Week 52 + 5 days	AE: any new untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued the study due to any AEs were recorded.
Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF): Hematology	OT: From start of study therapy through Week 52 + 5 days; OF= End of OT period + 24-week follow-up	Criteria for hematology abnormalities were graded using the modified WHO grading system. Hemoglobin: \<=11.0 g/dL; White Blood Cells: \<4000/mm\^3; Absolute Neutrophils (includes absolute bands): \<1500/mm\^3; Platelets: \<=99,000/mm\^3; International Normalized Ratio: ≥ 1.5 and ≥ 0.5 from baseline.
Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) : Serum Chemistry	OT: From start of study therapy through Week 52 + 5 days; OF= End of OT period + 24-week follow-up	The modified World Health Oranization(WHO)grading system was used to grade the abnormalities. ULN=upper limit of normal. Alanine aminotransferase:\>1.25xULN, Aspartate aminotransferase:\>1.25xULN, Alkaline Phosphatase:\>1.25xULN, Total Bilirubin:\>1.1xULN, Serum Lipase:\>1.10xULN, Creatinine:\>1.1xULN, Blood Urea Nitrogen:1.25xULN, Hyperglycemia:\>116 mg/dL, Hypoglycemia:\<64 mg/dL, Hyponatremia:\<132meq/L, Hypokalemia:\<3.4 meq/L, Albumin:≥1g/dL decrease from baseline, \<3 g/dL; Hypernatremia:\>148 meq/L, Hyperkalemia:\>5.6 meq/L, Hypokalemia:\<3.4 meq/L, Hyperchloremia:\>113 meq/L, Hypochloremia:\<93 meq/L

Trial Locations

Locations (15): Alabama Liver & Digestive Specialists (Alds)
🇺🇸
Montgomery, Alabama, United States
University Of Arizona
🇺🇸
Tucson, Arizona, United States
Empire International Research
🇺🇸
Miami, Florida, United States
University Of Miami
🇺🇸
Miami, Florida, United States
Banks Hepatology Institute, Pc
🇺🇸
College Park, Maryland, United States
Va New York Harbor Healthcare System
🇺🇸
New York, New York, United States
Brigham And Women'S Hospital
🇺🇸
Boston, Massachusetts, United States
Albert Einstein Healthcare Network
🇺🇸
Philadelphia, Pennsylvania, United States
Westchester Digestive Disease Group, Llp
🇺🇸
Yonkers, New York, United States
Alamo Medical Research
🇺🇸
San Antonio, Texas, United States
Local Institution
🇿🇦
Goodwood, Western Cape, South Africa
University Of Chicago
🇺🇸
Chicago, Illinois, United States
Hunter Holmes Mcguire D V A M C
🇺🇸
Richmond, Virginia, United States
L L C Bda The Research Institute
🇺🇸
Springfield, Massachusetts, United States
George Washington University Medical Center
🇺🇸
Washington, District of Columbia, United States