A Study to Evaluate Tenofovir Disoproxil Fumarate (DF) in Asian-American Adults With Chronic Hepatitis B Infection

A Phase IV Study to Evaluate the Efficacy, Safety and Tolerability of Tenofovir DF in Asian-American Adults With Chronic Hepatitis B Infection

The purpose of this study is to evaluate the antiviral activity and safety of tenofovir disoproxil fumarate (TDF) in Asian-American adults (self-reported Asian descent, living in the United States) with chronic hepatitis B infection. All participants will receive active treatment with TDF for 48 weeks.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: Tenofovir disoproxil fumarate

Detailed Description

Efficacy of TDF will be evaluated for reductions in serum HBV DNA, changes in liver enzymes, and the generation of antibody to the virus. Safety will be assessed by evaluating adverse events, laboratory abnormalities, and the development of drug resistance mutations.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Fountain Valley, California, United States, 92708
    • Hacienda Heights, California, United States, 91745
    • Los Angeles, California, United States, 90057
    • Monterey Park, California, United States, 91754
    • Mountain View, California, United States, 94040
    • Oakland, California, United States, 94609
    • Palo Alto, California, United States, 94304
    • San Jose, California, United States, 95128
  • Connecticut
    • Hamden, Connecticut, United States, 06518
  • Maryland
    • Baltimore, Maryland, United States, 21234
    • Laurel, Maryland, United States, 20707
    • Silver Spring, Maryland, United States, 20902
  • New Jersey
    • Englewood, New Jersey, United States, 07631
  • New York
    • Brooklyn, New York, United States, 11219
    • Flushing, New York, United States, 11355
    • New York, New York, United States, 10013
    • New York, New York, United States, 10038
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
  • Virginia
    • Fairfax, Virginia, United States, 22030
    • Falls Church, Virginia, United States, 22044
  • Washington
    • Bellevue, Washington, United States, 98004

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female
• Asian-American, defined as a person of self-reported Asian ancestry who is residing in the United States (US)
• 18 through 75 years of age, inclusive
• Documented chronic HBV infection, defined as positive serum HBsAg =/> 6 months
• HBV DNA =/> 10,000 copies/mL (PCR method)
• ALT > ULN and </= 10 × ULN at screening or within the past 12 months prior to screening
• Willing and able to provide written informed consent
• Negative serum beta-human chorionic gonadotropin (HCG) pregnancy test (females of child-bearing potential)
• Estimated glomerular filtration rate (creatinine clearance) =/> 60 mL/min/1.73m^2 by the Cockcroft-Gault equation
• Adequate hematologic function (absolute neutrophil count =/> 1,500/mm^3; hemoglobin =/> 10.0 g/dL)
• No prior TDF therapy; participants may have taken < 12 weeks of oral anti-HBV therapy, with the last dose =/> 16 weeks prior to screening; participants may have received prior interferon, but must have discontinued interferon therapy =/> 6 months prior to screening

Exclusion Criteria:

Participants who meet any of the following exclusion criteria are not to be enrolled in this study.

• Pregnant women, women who are breast feeding or who believe they may wish to become pregnant during the course of the study.
• Males and females of reproductive potential who are not willing to use an effective method of contraception during the study. For males, condoms should be used and for females, a barrier contraception method should be used in combination with one other form of contraception.
• Decompensated liver disease defined as direct (conjugated) bilirubin > 1.2 X ULN, prothrombin time (PT) > 1.2 X ULN, platelets < 150,000/mm3, or serum albumin < 3.5 g/dL
• Prior history of clinical hepatic decompensation (eg, ascites, jaundice, encephalopathy) or variceal hemorrhage
• Receipt of prior TDF treatment
• Receipt of =/> 12 weeks of oral anti-HBV nucleoside/nucleotide therapy, or receipt of ANY oral anti-HBV treatment < 16 weeks prior to screening
• Receipt of interferon (pegylated or not) therapy within 6 months of the Screening Visit
• alpha-fetoprotein > 50 ng/mL
• Evidence of hepatocellular carcinoma (HCC)
• Co-infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis D virus (HDV)
• History of significant renal disease (eg, nephrotic syndrome, renal dysgenesis, polycystic kidney disease, congenital nephrosis, acute tubular necrosis, other renal disease)
• History of significant bone disease (eg, osteomalacia, chronic osteomyelitis, osteogenesis imperfecta, osteochrondroses, multiple bone fractures)
• Significant cardiovascular, pulmonary or neurological disease
• Evidence of a gastrointestinal malabsorption syndrome that may interfere with absorption of orally administered medications
• History of solid organ or bone marrow transplantation
• Ongoing therapy with any of the following: nephrotoxic agents, competitors of renal excretion (eg, probenecid), systemic chemotherapeutic agents, systemic corticosteroids, Interleukin-2 (IL-2) and other immunomodulating agents, investigational agents (except with the expressed approval of the Sponsor); administration of any of the above medications must be discontinued at least 30 days prior to the Baseline Visit and for the duration of the study period
• Known hypersensitivity to the study drugs, the metabolites, or formulation excipients
• Any other condition (including alcohol or substance abuse) or prior therapy that, in the opinion of the Investigator, would make the participant unsuitable for the study or unable to comply with dosing requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TDF; 300-mg tablet (marketed formulation) taken orally once daily	Drug: Tenofovir disoproxil fumarate; 300-mg tablet (marketed formulation) taken orally once daily; Other Names: Viread

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) <400 Copies/mL (<69 IU/mL)	Blood samples were collected from study participants for measuring HBV DNA via polymerase chain reaction (PCR) method.	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Alanine Aminotransferase (ALT) Normal at Week 48	Number of participants with normal ALT (at or below the upper limit of normal [ULN] for the central laboratory [34 U/L])at Week 48	Week 48
Number of Participants With ALT Normalized (Baseline Values > ULN [34 U/L] and <= ULN at a Subsequent Visit) at Week 48	A normal value at Week 48 after having elevated ALT at baseline; normal ALT is defined as being at or below the ULN for the central laboratory (34 U/L)	Week 48
Number of Participants With Composite Endpoint of Hepatitis B Virus (HBV) DNA <400 Copies/mL (<69 IU/mL) and Normal ALT at Week 48	Blood samples were collected for evaluating serum chemistry, including determination of ALT, and for measuring HBV DNA via PCR method. Composite endpoints proposed in the protocol included the percentage of participants with HBV DNA < 400 copies/mL (<69 IU/mL) and normal ALT (ALT <= ULN [34 U/L]); and with HBV DNA < 400 copies/mL, normal ALT, and HBeAg loss/seroconversion. Because so few participants lost hepatitis B e antigen (HBeAg) or developed antibody to hepatitis B e antigen (anti-HBe), only the composite endpoint of HBV DNA < 400 copies/mL and normal ALT was analyzed.	Week 48
Change From Baseline in FibroTest Value	The FibroTest score is used to assess liver fibrosis and is calculated based on a formula including the participant's age and sex and 5 laboratory parameters: alpha 2 macroglobulin, haptoglobin, gamma-glutamyl transferase (GGT), bilirubin, and apolipoprotein A1. Scores can range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis.	Baseline and Week 48
Number of Participants With HBeAg/Hepatitis B Surface Antigen (HBsAg) Loss and Seroconversion	HBeAg/HBsAg loss is defined for an individual participant as HBeAg+/HBsAg+ at baseline and HBeAg-/HBsAg- at Week 48. HBeAg/HBsAg serocoversion is defined for an individual participant as HBeAg+/HBsAg+ at baseline and HBeAg-/HBsAg- and anti-HBe+/antibody to hepatitis B surface antigen+ (anti-HBs+) at Week 48.	Week 48
Number of Participants With HBV DNA < 169 Copies/mL (<29 IU/mL) at Week 48	Blood samples from study participants were collected for measuring HBV DNA via PCR method.	Week 48
Number of Participants With Composite Endpoint of HBV DNA <400 Copies/mL (<69 IU/mL), Normal ALT, and HBeAg Loss	Composite endpoints proposed in the protocol included the percentage of participants with HBV DNA < 400 copies/mL (<69 IU/mL) and normal ALT (ALT <= ULN [34 U/L]); and with HBV DNA < 400 copies/mL, normal ALT, and HBeAg loss/seroconversion. Because so few participants lost HBeAg or seroconverted to anti-HBe, only the composite endpoint of HBV DNA < 400 copies/mL and normal ALT was analyzed.	Week 48
Number of Participants With Composite Endpoint of HBV DNA <400 Copies/mL (<69 IU/mL), Normal ALT, and Seroconversion to Anti-HBe	Composite endpoints proposed in the protocol included the percentage of participants with HBV DNA < 400 copies/mL (<69 IU/mL) and normal ALT (ALT <= ULN); and with HBV DNA < 400 copies/mL, normal ALT, and HBeAg loss/seroconversion. Because so few participants lost HBeAg or seroconverted to anti-HBe, only the composite endpoint of HBV DNA < 400 copies/mL and normal ALT was analyzed.	Week 48
Summary of Resistance Surveillance for Participants Without Virologic Breakthrough	Serum was collected for HBV resistance surveillance, and sequence analysis of the HBV polymerase was assessed through di-deoxy sequencing of baseline and postbaseline samples.	Week 48
Summary of Resistance Surveillance for Participants With Virologic Breakthrough	Serum was collected for HBV resistance surveillance, and sequence analysis of the HBV polymerase was assessed through di-deoxy sequencing of baseline and postbaseline samples.	Week 48
Summary of Resistance Surveillance for Participants Who Discontinued the Study Early	Serum was collected for HBV resistance surveillance, and sequence analysis of the HBV polymerase was assessed through di-deoxy sequencing of baseline and postbaseline samples.	Week 48

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Pan CQ, Chan S, Trinh H, Yao A, Bae H, Lou L. Similar efficacy and safety of tenofovir in Asians and non-Asians with chronic hepatitis B. World J Gastroenterol. 2015 May 14;21(18):5524-31. doi: 10.3748/wjg.v21.i18.5524.
• Pan CQ, Trinh H, Yao A, Bae H, Lou L, Chan S; Study 123 Group. Efficacy and safety of tenofovir disoproxil fumarate in Asian-Americans with chronic hepatitis B in community settings. PLoS One. 2014 Mar 4;9(3):e89789. doi: 10.1371/journal.pone.0089789. eCollection 2014. Erratum In: PLoS One. 2014;9(5):e98723.

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: August 13, 2008
• First Submitted That Met QC Criteria: August 14, 2008
• First Posted (Estimate): August 15, 2008

Study Record Updates

• Last Update Posted (Estimate): December 5, 2011
• Last Update Submitted That Met QC Criteria: November 30, 2011
• Last Verified: November 1, 2011

More Information

Terms related to this study

• Keywords: Hepatitis; Hepatitis B; Tenofovir disoproxil fumarate; Tenofovir DF; Asian-American
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir
• Other Study ID Numbers: GS-US-174-0123