Evaluation of Tenofovir Disoproxil Fumarate in Adolescents With Chronic Hepatitis B Infection - Full Text View

Sponsor:	Gilead Sciences
Information provided by:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT00734162

Purpose

The primary purpose of the study is to evaluate the effectiveness, safety, and tolerability of tenofovir DF in adolescents (aged 12-17 years) with chronic hepatitis B infection.

Condition	Intervention	Phase
Hepatitis B	Drug: tenofovir disoproxil fumarate Drug: placebo	Phase II Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Randomized, Double-Blind Evaluation of the Antiviral Efficacy, Safety, and Tolerability of Tenofovir Disoproxil Fumarate Versus Placebo in Adolescents With Chronic Hepatitis B Infection

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis B

Drug Information available for: Tenofovir Tenofovir disoproxil Tenofovir Disoproxil Fumarate Recombinant hepatitis B vaccine Hepatitis B Vaccines Hepatitis A Vaccines

U.S. FDA Resources

Further study details as provided by Gilead Sciences:

Primary Outcome Measures:

The primary efficacy endpoint is a composite endpoint of HBV DNA < 400 copies/mL and ALT normal [ Time Frame: After 72 weeks of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Adverse events and clinical laboratory tests will be collected at every visit throughout the study. [ Time Frame: Throughout entire 192 weeks of study duration ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	100
Study Start Date:	September 2008
Estimated Study Completion Date:	April 2013
Estimated Primary Completion Date:	March 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: B Blinded tenofovir placebo PO once daily	Drug: placebo placebo tablet to match active drug (tenofovir)
Experimental: A Blinded tenofovir DF 300 mg PO once daily	Drug: tenofovir disoproxil fumarate 300 mg tablet, once daily Other Name: Viread

Detailed Description:

The optimal treatment for adolescents with chronic HBV infection is currently unknown. Treatment with interferon alfa, lamivudine and adefovir in pediatric populations has been shown to be less than optimal. Further, the safety and efficacy of entecavir and telbivudine have not been established in patients < 16 years of age. A study evaluating tenofovir DF in adolescents (ages 12-17) is needed to assess the safety and efficacy of this agent in the treatment of chronic hepatitis B in this patient population. In addition, the study will help to further elucidate the pharmacokinetic and resistance profiles of tenofovir DF. Through their participation, study subjects will help generate critical new information to help guide the most optimal treatment of chronic HBV infection in adolescents.

This is a randomized, double-blind study to evaluate the antiviral efficacy, safety and tolerability of tenofovir DF versus placebo in adolescents with chronic HBV infection. One hundred (100) tenofovir DF-naïve subjects will be randomized in a 1:1 ratio to treatment arm A or B:

Treatment A: Blinded tenofovir DF 300 mg PO once daily Treatment B: Blinded matching placebo PO once daily

After 72 weeks of blinded treatment, all subjects will switch to open-label tenofovir DF for an additional 2.5 years of treatment, provided that no safety concerns are identified by the independent Data Monitoring Committee monitoring the study.

Eligibility

Ages Eligible for Study:	12 Years to 17 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria

Male or female, 12 through 17 years of age, inclusive (consent of parent/legal guardian required)
Documented chronic HBV infection
HBeAg positive
Weight > 35 kg
Able to swallow oral tablets
HBV DNA > 100,000 copies/mL (PCR method)
ALT > 2 × upper limit of normal (ULN) at screening, OR any history of ALT > 2 × ULN over the past 24 months
Willing and able to provide written informed consent/assent (child and parent/legal guardian)
Negative serum pregnancy test (for post-menarchal females only)
Estimated glomerular filtration rate (creatinine clearance) > 80 mL/min/1.73m2
Adequate hematologic function (absolute neutrophil count >/= 1,500/mm3; hemoglobin >/= 10.0 g/dL)
No prior tenofovir DF therapy (subjects may have received prior interferon or oral anti-HBV nucleoside/nucleotide therapy; subjects must have discontinued interferon therapy >/= 6 months prior to screening; subjects experienced on anti-HBV nucleoside/nucleotide therapy must have discontinued therapy >/= 16 weeks prior to screening to avoid flare if randomized to the placebo arm)

Exclusion Criteria

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.
Decompensated liver disease
Receipt of interferon (pegylated or not) therapy within 6 months of the Screening Visit
Receipt of anti-HBV nucleoside/nucleotide therapy within 16 weeks of the Screening Visit
alpha fetoprotein > 50 ng/mL
Evidence of hepatocellular carcinoma (HCC)
Co infection with HIV, HCV, or HDV
History of significant renal disease (e.g., nephrotic syndrome, renal dysgenesis, polycystic kidney disease, congenital nephrosis, acute tubular necrosis, other renal disease)
History of significant bone disease (e.g., osteomalacia, chronic osteomyelitis, osteogenesis imperfecta, osteochondroses, 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 nephrotoxic agents, competitors of renal excretion, systemic chemotherapeutic agents, systemic corticosteroids, interleukin 2 (IL 2) and other immunomodulating agents, investigational agents.
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 subject unsuitable for the study or unable to comply with dosing requirements

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00734162

Show 31 Study Locations

Sponsors and Collaborators

Gilead Sciences

Investigators

Study Director:

Stephen J Rossi, PharmD

Gilead Sciences

More Information

No publications provided

Responsible Party:	Stephen Rossi, PharmD/ Sr. Director, Clinical Research, Gilead Sciences
ClinicalTrials.gov Identifier:	NCT00734162 History of Changes
Other Study ID Numbers:	GS-US-174-0115
Study First Received:	August 13, 2008
Last Updated:	January 5, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Gilead Sciences:

tenofovir
adolescents
chronic hepatitis B

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 disoproxil
Tenofovir
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 February 09, 2012