Clinical trial NCT00736190: A Study to Evaluate Tenofovir Disoproxil Fumarate (DF) in Asian-American Adults With Chronic Hepatitis B Infection
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Hepatitis B
Keywords: Hepatitis B
Hepatitis
Tenofovir disoproxil fumarate
Tenofovir DF
Asian-American
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2008-08-15
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Number of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) <400 Copies/mL (<69 IU/mL)
timeFrame: Week 48
Secondary outcomes:
measure: Number of Participants With Alanine Aminotransferase (ALT) Normal at Week 48
timeFrame: Week 48
measure: Number of Participants With ALT Normalized (Baseline Values > ULN [34 U/L] and <= ULN at a Subsequent Visit) at Week 48
timeFrame: Week 48
measure: Number of Participants With Composite Endpoint of Hepatitis B Virus (HBV) DNA <400 Copies/mL (<69 IU/mL) and Normal ALT at Week 48
timeFrame: Week 48
measure: Change From Baseline in FibroTest Value
timeFrame: Baseline and Week 48
measure: Number of Participants With HBeAg/Hepatitis B Surface Antigen (HBsAg) Loss and Seroconversion
timeFrame: Week 48
measure: Number of Participants With HBV DNA < 169 Copies/mL (<29 IU/mL) at Week 48
timeFrame: Week 48
measure: Number of Participants With Composite Endpoint of HBV DNA <400 Copies/mL (<69 IU/mL), Normal ALT, and HBeAg Loss
timeFrame: Week 48
measure: Number of Participants With Composite Endpoint of HBV DNA <400 Copies/mL (<69 IU/mL), Normal ALT, and Seroconversion to Anti-HBe
timeFrame: Week 48
measure: Summary of Resistance Surveillance for Participants Without Virologic Breakthrough
timeFrame: Week 48
measure: Summary of Resistance Surveillance for Participants With Virologic Breakthrough
timeFrame: Week 48
measure: Summary of Resistance Surveillance for Participants Who Discontinued the Study Early
timeFrame: Week 48
Other outcomes:
Locations:
city: Fountain Valley
country: United States
state: California
city: Hacienda Heights
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Monterey Park
country: United States
state: California
city: Mountain View
country: United States
state: California
city: Oakland
country: United States
state: California
city: Palo Alto
country: United States
state: California
city: San Jose
country: United States
state: California
city: Hamden
country: United States
state: Connecticut
city: Baltimore
country: United States
state: Maryland
city: Laurel
country: United States
state: Maryland
city: Silver Spring
country: United States
state: Maryland
city: Englewood
country: United States
state: New Jersey
city: Brooklyn
country: United States
state: New York
city: Flushing
country: United States
state: New York
city: New York
country: United States
state: New York
city: New York
country: United States
state: New York
city: Philadelphia
country: United States
state: Pennsylvania
city: Fairfax
country: United States
state: Virginia
city: Falls Church
country: United States
state: Virginia
city: Bellevue
country: United States
state: Washington
Study officials:
References:
citation: 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.
citation: 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.