Evaluating the Efficacy, Safety and Tolerability of Tenofovir DF in Pediatric Patients With Chronic Hepatitis B Infection

• Proportion of patients with HBeAg seroconversion at week 72 [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
• Cumulative Incidence of at least 4% decrease from baseline in bone mineral density of lumbar spine [ Time Frame: Week 72 ] [ Designated as safety issue: Yes ]
• Percent change from baseline in bone mineral density of lumbar spine [ Time Frame: Week 72 ] [ Designated as safety issue: Yes ]
• Safety and Tolerability of Therapy [ Time Frame: Up to Week 192 ] [ Designated as safety issue: Yes ]
  Safety and tolerability is measured by the frequency of laboratory abnormalities reported as adverse events.
• Biochemical and serological responses [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
  Biochemical and serological responses as measured by normal/normalization of ALT, proportion of subjects with HBV DNA < 400 copies/mL and normal ALT, proportion of subjects with HBV DNA < 169 copies/mL, proportion of subjects with HBsAg loss and seroconversion
• Viral Resistance [ Time Frame: Weeks 72, 144, 192 or Early Discontinuation ] [ Designated as safety issue: No ]
  Genotypic changes from baseline within the HBV polymerase for patients who were viremic (HBV DNA > or equal 400 copies/mL) with confirmed virologic breakthrough

This placebo-controlled study evaluates the efficacy, safety and tolerability of TDF in patients 2 to <12 years old with chronic Hepatitis B infection. While studies have shown significant virologic response in adults and adolescents, the effect in children is not well established. This study will provide valuable data that can help establish the efficacy and safety profiles of TDF in children.

• Drug: Tenofovir DF

  Tenofovir disoproxil fumarate oral tablet / oral powder

  • subjects ≥ 17 kg: one tablet once daily (150, 200, 250 or 300 mg tablets based on body weight) or oral powder if unable to swallow a tablet.

  Other Names:

  • VIREAD
  • Tenofovir disoproxil fumarate
  • TDF
  • Tenofovir
  • Tenofovir DF
• Drug: Tenofovir DF Placebo

  Matching placebo oral tablet / oral powder

  • subjects ≥ 17 kg: one tablet once daily (matching of physical appearance as the corresponding active tablet) or matching oral placebo powder
  • subjects < 17 kg and subjects ≥ 17 kg who are unable to swallow a tablet will receive once daily matching oral placebo powder
  Other Names:

  • VIREAD
  • Tenofovir disoproxil fumarate
  • TDF
  • Tenofovir
  • Tenofovir DF

• Experimental: Tenofovir DF
  Tenofovir disoproxil fumarate oral tablet / oral powder
  Intervention: Drug: Tenofovir DF
• Placebo Comparator: Tenofovir DF Placebo
  Intervention: Drug: Tenofovir DF Placebo

Inclusion Criteria:

• Male or Female, 2 to <12 years of age
• Weight ≥ 10kg
• Chronic HBV infection ≥ 6 months
• HBeAg-positive or HBeAg-negative
• HBV Viral Load ≥ 100,000 copies/mL
• ALT ≥ 1.5 x ULN at screening
• Creatinine Clearance ≥ 80mL/min
• ANC ≥ 1,500/mm^3, hemoglobin ≥ 10g/dL
• Negative pregnancy test at screening
• No prior tenofovir DF therapy (subjects may have received prior interferon‑alfa and/or other oral anti‑HBV nucleoside/nucleotide therapy; subjects must have discontinued interferon-alfa therapy ≥ 6 months prior to screening; subjects experienced on other 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 or lactating
• Decompensated liver disease
• Received interferon therapy within 6 months of Screening
• Received anti-HBV nucleoside/nucleotide therapy within 16 weeks of Screening
• Alpha-fetoprotein levels > 50ng/mL
• Evidence of hepatocellular carcinoma (HCC)
• Co-infection with HIV, acute HAV, HCV, or HDV
• Chronic liver disease not due to HBV
• History of significant renal, cardiovascular, pulmonary, neurological or bone disease
• Long term non-steroidal, anti-inflammatory drug therapy