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

Hepatitis B Infection Clinical Trial

Official title:

A Study to Describe the Antiviral Effect of Entecavir (ETV) in Blacks/African Americans and Hispanics With Chronic Hepatitis B Virus (HBV) Infection Who Are Nucleoside-Naive

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00371150
• Other study ID #: AI463-085
• Status: Completed
• Phase: Phase 4
• First received: August 29, 2006
• Last updated: March 22, 2012
• Start date: November 2006
• Est. completion date: March 2011

Study information

• Verified date: March 2012
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 131
• Est. completion date: March 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B Infection
• Hepatitis B, Chronic
• Hepatitis, Chronic
• Infection

Intervention

Drug:
• Entecavir
Tablets, Oral, 0.5 mg, once daily, up to 52 weeks

Locations

Country	Name	City	State
Brazil	Local Institution	Belo Horizonte - Mg	Minas Gerais
Brazil	Local Institution	Campinas	Sao Paulo
Brazil	Local Institution	Rio De Janeiro - Rj	Rio De Janeiro
Brazil	Local Institution	Salvador	Bahia
Brazil	Local Institution	Sao Paulo - Sp	Sao Paulo
Mexico	Local Institution	Df	Distrito Federal
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Zapopan	Jalisco
Puerto Rico	Local Institution	Santurce
South Africa	Local Institution	Belville	Western Cape
South Africa	Local Institution	Goodwood	Western Cape
United States	Brigham And Women'S Hospital	Boston	Massachusetts
United States	University Of Chicago	Chicago	Illinois
United States	Banks Hepatology Institute, Pc	College Park	Maryland
United States	Empire International Research	Miami	Florida
United States	University Of Miami	Miami	Florida
United States	Alabama Liver & Digestive Specialists (Alds)	Montgomery	Alabama
United States	Va New York Harbor Healthcare System	New York	New York
United States	Albert Einstein Healthcare Network	Philadelphia	Pennsylvania
United States	Hunter Holmes Mcguire D V A M C	Richmond	Virginia
United States	Alamo Medical Research	San Antonio	Texas
United States	L L C Bda The Research Institute	Springfield	Massachusetts
United States	University Of Arizona	Tucson	Arizona
United States	George Washington University Medical Center	Washington	District of Columbia
United States	Westchester Digestive Disease Group, Llp	Yonkers	New York

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Brazil,  Mexico,  Puerto Rico,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With HBV Deoxyribonucleic Acid (DNA) < 50 IU/mL by Polymerase Chain Reaction (PCR) at Week 48	HBV DNA assessments were performed using the Roche COBAS® TaqMan AmpliPrep assay. HBV DNA < 50 IU/mL = approximately <300 copies/mL.	Week 48 of ETV treatment	No
Secondary	Percentage of Participants Who Achieve HBV DNA < Lower Limit of Quantitation (LOQ = 29 IU/mL [Approximately 169 Copies/mL]) at 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.	Week 48	No
Secondary	Percentage of Participants With HBV DNA by PCR Category at Week 48	HBV DNA assessments were performed using the Roche COBAS® TaqMan AmpliPrep assay.	Week 48	No
Secondary	Percentage of Participants With Virologic Rebound Through Week 48 While on Continued Dosing With ETV	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)	through Week 48	No
Secondary	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at 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.	Week 48	No
Secondary	Percentage of Participants With Confirmed HBeAg Loss at Week 48 (for HBeAg-positive Participants Only)	HBeAg is a hepatitis B viral protein. HBeAg loss = HBeAg-negative at the specified analysis week	Week 48	No
Secondary	Percentage of Participants With HBeAg Seroconversion at Week 48 (for HBeAg-positive Participants Only)	HBeAg is a hepatitis B viral protein. HBeAg Seroconversion = HBeAg Loss and Presence of Hepatitis B e Antibody (HBeAb).	Week 48	No
Secondary	Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at 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.	Week 48	No
Secondary	Percentage of Participants With HBsAg Seroconversion at 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.	Week 48	No
Secondary	Mean log10 Reduction From Baseline in HBV DNA at Week 48	HBV DNA was analyzed by PCR, using the Roche COBAS®TaqMan TaqMan AmpliPrep assay. Reduction in log10 HBV count=reduced viral load.	baseline, Week 48	No
Secondary	Percentage of Participants With HBV DNA < Other IU Cut-off Points That May be Clinically Relevant at the Time of Data Analysis		Week 48	No
Secondary	Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations From Study Drug Due to Adverse Events	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.	From enrollment through Week 52 + 5 days	Yes
Secondary	Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF): Hematology	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.	OT: From start of study therapy through Week 52 + 5 days; OF= End of OT period + 24-week follow-up	Yes
Secondary	Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) : Serum Chemistry	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	OT: From start of study therapy through Week 52 + 5 days; OF= End of OT period + 24-week follow-up	Yes

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form