Evaluation of Tenofovir Disoproxil Fumarate in Adolescents With Chronic Hepatitis B Infection
Condition: Hepatitis B Virus (HBV)
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic
Intervention: Tenofovir disoproxil fumarate (TDF); Placebo
Intervention description: TDF administered as a 300-mg tablet once daily; TDF placebo tablet once daily
Intervention MeSH terms: Tenofovir
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 106.0
Sex: All
Minimum age: 12 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: tenofovir; adolescents; chronic hepatitis B

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.
    

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