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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00736190
First received: August 13, 2008
Last updated: November 30, 2011
Last verified: November 2011
  Purpose

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.


Condition Intervention Phase
Chronic Hepatitis B
Drug: Tenofovir disoproxil fumarate
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase IV Study to Evaluate the Efficacy, Safety and Tolerability of Tenofovir DF in Asian-American Adults With Chronic Hepatitis B Infection

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Number of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) <400 Copies/mL (<69 IU/mL) [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Blood samples were collected from study participants for measuring HBV DNA via polymerase chain reaction (PCR) method.


Secondary Outcome Measures:
  • Number of Participants With Alanine Aminotransferase (ALT) Normal at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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

  • Number of Participants With ALT Normalized (Baseline Values > ULN [34 U/L] and <= ULN at a Subsequent Visit) at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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)

  • Number of Participants With Composite Endpoint of Hepatitis B Virus (HBV) DNA <400 Copies/mL (<69 IU/mL) and Normal ALT at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in FibroTest Value [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With HBeAg/Hepatitis B Surface Antigen (HBsAg) Loss and Seroconversion [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With HBV DNA < 169 Copies/mL (<29 IU/mL) at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Blood samples from study participants were collected for measuring HBV DNA via PCR method.

  • Number of Participants With Composite Endpoint of HBV DNA <400 Copies/mL (<69 IU/mL), Normal ALT, and HBeAg Loss [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Composite Endpoint of HBV DNA <400 Copies/mL (<69 IU/mL), Normal ALT, and Seroconversion to Anti-HBe [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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.

  • Summary of Resistance Surveillance for Participants Without Virologic Breakthrough [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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.

  • Summary of Resistance Surveillance for Participants With Virologic Breakthrough [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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.

  • Summary of Resistance Surveillance for Participants Who Discontinued the Study Early [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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.


Enrollment: 90
Study Start Date: August 2008
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Viread

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00736190

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
United States, Connecticut
Hamden, Connecticut, United States, 06518
United States, Maryland
Baltimore, Maryland, United States, 21234
Laurel, Maryland, United States, 20707
Silver Spring, Maryland, United States, 20902
United States, New Jersey
Englewood, New Jersey, United States, 07631
United States, New York
Brooklyn, New York, United States, 11219
Flushing, New York, United States, 11355
New York, New York, United States, 10038
New York, New York, United States, 10013
United States, Pennsylvania
Philadelphia, Pennsylvania, United States, 19107
United States, Virginia
Fairfax, Virginia, United States, 22030
Falls Church, Virginia, United States, 22044
United States, Washington
Bellevue, Washington, United States, 98004
Sponsors and Collaborators
Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT00736190     History of Changes
Other Study ID Numbers: GS-US-174-0123
Study First Received: August 13, 2008
Results First Received: July 7, 2011
Last Updated: November 30, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
Hepatitis B
Hepatitis
Tenofovir disoproxil fumarate
Tenofovir DF
Asian-American

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Tenofovir
Tenofovir disoproxil
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on April 17, 2014