A study in children with long-lasting Hepatitis B infection to assess the effectiveness and safety of the drug Viread

INTERVENTION: Trade Name: VIREAD Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: TENOFOVIR DISOPROXIL (as FUMARATE) CAS Number: 202138‐50‐9 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 300‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use Product Name: Tenofovir Disoproxil Fumarate Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: TENOFOVIR DISOPROXIL (as FUMARATE) CAS Number: 202138‐50‐9 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 250‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use Product Name: Tenofovir Disoproxil Fumarate Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: TENOFOVIR DISOPROXIL (as FUMARATE) CAS Number: 202138‐50‐9 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 200‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use Product Name: Tenofovir Disoproxil Fumarate Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: TENOFOVIR DISOPROXIL (as FUMARATE) CAS Number: 202138‐50‐9 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 150‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use Product Name: Tenofovir Disoproxil Fumarate Pharmaceutical Form: Oral powder INN or Proposed INN: TENOFOVIR DISOPROXIL (as FUMARATE) CAS Number: 202138‐50‐9 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 300‐ Pharmaceutical form of the placebo: Oral powder Route of administration of the placebo: Oral use CONDITION: Chronic Hepatitis B ; MedDRA version: 14.1 Level: PT Classification code 10008910 Term: Chronic hepatitis B System Organ Class: 10021881 ‐ Infections and infestations Therapeutic area: Diseases [C] ‐ Virus Diseases [C02] PRIMARY OUTCOME: Main Objective: The primary objective of this study is to evaluate the antiviral efficacy of tenofovir DF versus; placebo in pediatric patients (aged 2 to < 12 years, at the time; of enrollment) with chronic hepatitis B infection Primary end point(s): The primary efficacy endpoint is the proportion of patients with; serum HBV DNA < 400 copies/mL at Week 72 in each arm. Secondary Objective: To evaluate the proportion of subjects with HBeAg seroconversion at Week 72 (in subjects with baseline HBeAg sero‐positivity); ; To characterize the safety and tolerability profile of tenofovir; DF in pediatric patients (aged 2 to < 12 years, at the time of; enrollment) with chronic hepatitis B infection; ; To evaluate the biochemical and serological responses to; tenofovir DF versus placebo; ; To evaluate the incidence of potential resistance mutations to; tenofovir DF in the hepatitis B virus polymerase/reverse; transcriptase (pol/RT); ; To assess the pharmacokinetics of tenofovir in subjects receiving the tablet formulation and those receiving the oral powder formulation Timepoint(s) of evaluation of this end point: Week 72 SECONDARY OUTCOME: Secondary end point(s): The proportion of subjects with; HBeAg seroconversion (in subjects with baseline HBeAg; sero‐positivity only) at Week 72; ; The proportion of subjects with normal ALT and normalization of; ALT; ; The composite endpoint of proportion of subjects with HBV DNA; < 400 copies/mL and normal ALT; ; The proportion of subjects with HBV DNA < 169 copies/mL; ; The proportions of subjects with HBsAg loss and seroconversion; ; The genotypic changes from baseline within the HBV polymerase; for subjects who were viremic (HBV DNA = 400 copies/mL); at Weeks 72, 144, 192 or Early Discontinuation; with; confirmed virologic breakthrough; ; Cumulative incidence of at least a 4% decrease from baseline in bone mineral density of lumbar spine ; ; Percent change from baseline in bone mineral density of lumbar spine; Timepoint(s) of evaluation of this end point: Weeks 72, 96 and / or 192 INCLUSION CRITERIA: • Male or female • 2 years to < 12 years of age (consent of parent or legal guardian required) • Body weigh = 10kg • Documented chronic HBV infection, defined as positive serum HBsAg = 6 months • HBeAg‐positive or HBeAg‐negative • HBV DNA = 105 copies/mL (PCR method) • ALT = 1.5 × ULN at screening, • Estimated glomerular filtration rate (creatinine clearance) = 80 mL/min/1.73m2 ‐Estimated creatinine clearance using Schwartz Formula (mL/min/1.73m2) = k × L/Scr ‐[(k is a proportionality constant: pediatric males/females = 2 years to < 12 years k = 0.55; for adolescent females = 12 years old, k = 0.55, and for adolescent males = 12 years, k = 0.70); L is height in centimeters (cm); and Scr is serum creatinine (mg/dL)] • Adequate hematologic function (absolute neutrophil count = 1,500/mm3; hemoglobin = 10.0 g/dL) • Negative serum ß‐HCG pregnancy test (for females of childbearing potential only) • Male and female subjects of