Evaluation of Tenofovir Disoproxil Fumarate in Adolescents With Chronic Hepatitis B Infection

NCT ID: NCT00734162

Last Updated: 2016-09-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 106 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2015-12-31

Brief Summary

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

The optimal treatment for adolescents with chronic HBV infection is currently unknown. Treatment with interferon alfa, lamivudine, and adefovir dipivoxil 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 TDF in adolescents (ages 12-17) was 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 (PK) and resistance profiles of TDF. Through their participation, study participants 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 TDF versus placebo in adolescents with chronic HBV infection. TDF treatment-naive participants were randomized in a 1:1 ratio to TDF or placebo. After 72 weeks of blinded treatment, participants were to switch to open-label TDF for an additional 2.5 years of treatment, provided that no safety concerns are identified by the Independent Data Monitoring Committee monitoring the study.

Conditions

Hepatitis B Virus (HBV)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Tenofovir disoproxil fumarate (TDF)

Group Type: EXPERIMENTAL

Tenofovir disoproxil fumarate (TDF)

Intervention Type: DRUG

TDF administered as a 300-mg tablet once daily

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

TDF placebo tablet once daily

Interventions

Tenofovir disoproxil fumarate (TDF)

TDF administered as a 300-mg tablet once daily

Intervention Type: DRUG

Placebo

TDF placebo tablet once daily

Intervention Type: DRUG

Other Intervention Names

Viread®

Eligibility 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 or HBeAg negative
• Weight > 35 kg
• Able to swallow oral tablets
• HBV DNA > 100,000 copies/mL (polymerase chain reaction (PCR) method)
• Alanine aminotransferase (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 postmenarchal females only)
• Estimated glomerular filtration rate (creatinine clearance [using the Schwartz formula]) > 80 mL/min/1.73m^2
• Adequate hematologic function (absolute neutrophil count ≥ 1,500/mm^3; hemoglobin ≥ 10.0 g/dL)
• No prior TDF therapy (participants may have received prior interferon or oral anti-HBV nucleoside/nucleotide therapy; participants must have discontinued interferon therapy ≥ 6 months prior to screening; participants 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)
• Coinfection with 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, 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), or other immunomodulating or 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 participants unsuitable for the study or unable to comply with dosing requirements

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Benedetta Massetto, MD, PhD

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

Children's Hospital & Research Center at Oakland

Oakland, California, United States

Riley Hospital for Children

Indianapolis, Indiana, United States

Children's Hospital & Regional Medical Center, d/b/a Seattle Children's Research Institute

Seattle, Washington, United States

Multiprofile Hospital for Active Treatment Sveti Georgi

Plovdiv, , Bulgaria

Clinic of Gastroenterology, Specialized Hospital for Active Treatment of Pediatric Diseases, Sofia

Sofia, , Bulgaria

Hopital Femmes Meres Enfants

Bron, , France

Hôpital Claude Huriez

Lille, , France

Samodzielny Publiczny Dzieciecy Szpital Kliniczny Akademii Medycznej w Bialymstoku

Bialystok, , Poland

Wojewodzki Specjalistyczny Szpital im Bieganskiego

Bydgoszcz, , Poland

Wojewodzki Szpital Obserwacyjno-Zakazny im. T. Browicza

Bydgoszcz, , Poland

Krakowski Szpital Specjalistyczny im. Jana Pawla II

Krakow, , Poland

Samodzielny Publiczny Szpital Kliniczny im. Karola Johschera

Poznan, , Poland

Specjalistyczny Zespol Opieki Zdrowotnej nad Matka i Dzieckiem

Poznan, , Poland

Wojewodzki Szpital Zakazny

Warsaw, , Poland

Samodzielny Publiczny Szpital Kliniczny Nr 1

Wroclaw, , Poland

Fundeni Clinical Institute

Bucharest, , Romania

Institute for Infectious Diseases

Bucharest, , Romania

Cluj Childrens Emergency Hospital

Napaco, , Romania

Hosp Univ y Politecnico La Fe de Valencia

Madrid, , Spain

Hospital Universitario De Getafe

Madrid, , Spain

Ege Universitesi Tip Fakultesi Hastanesi

Izmir, , Turkey (Türkiye)

Countries

United States; Bulgaria; France; Poland; Romania; Spain; Turkey (Türkiye)

References

Murray KF, Szenborn L, Wysocki J, Rossi S, Corsa AC, Dinh P, McHutchison J, Pang PS, Luminos LM, Pawlowska M, Mizerski J. Randomized, placebo-controlled trial of tenofovir disoproxil fumarate in adolescents with chronic hepatitis B. Hepatology. 2012 Dec;56(6):2018-26. doi: 10.1002/hep.25818. Epub 2012 Aug 27.

Reference Type: RESULT

PMID: 22544804 (View on PubMed)

Other Identifiers

GS-US-174-0115

Identifier Type: -

Identifier Source: org_study_id