Pharmacoepidemiology study to define the long-term safety profile of tenofovir disoproxil fumarate (Tenofovir DF, Viread®) and describe the management of Tenofovir DF-associated renal and bone toxicity in Chronic Hepatitis B (CHB)-infected adolescents aged 12 to <18 years in Europe (Viread HBV PASS)

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Clinical trial

Clinical trials

• Clinical trial regulatory scope:
  Post-authorisation interventional clinical trial
• Clinical trial phase:
  Therapeutic use (Phase IV)
• Clinical trial randomisation:
  Randomised clinical trial

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (J05AF) Nucleoside and nucleotide reverse transcriptase inhibitors

  Nucleoside and nucleotide reverse transcriptase inhibitors
• Medical condition to be studied:
  Chronic hepatitis B

Population studied

• Short description of the study population:
  Patients with following criteria were included:; 1. Aged 12 to <16 years; 2. Weight ≥ 35 kg; 3. Documented chronic HBV infection (e.g. positive serum HBsAg ≥ 6 months); 4) Able to swallow oral tablets; 5) Negative serum β-HCG pregnancy test (for females of childbearing potential); 6) Estimated glomerular filtration rate (creatinine clearance) ≥ 80 mL/min/1.73m2 ; 7) Parent or legal guardian of potential study subjects able to provide written informed consent prior to any screening evaluations and willing to comply with study requirements or subject able to provide written assent as determined by IEC/local requirements and at the Investigator’s discretion.
• Age groups:
  • Paediatric Population (< 18 years)

    • Adolescents (12 to < 18 years)
• Special population of interest:
  Hepatic impaired
• Estimated number of subjects:
  30

Study design details

• Main study objective:
  To characterize the long term (i.e. 96 weeks of follow up) bone safety profile of open-label Tenofovir DF treatment in CHB-infected adolescents. This includes prospectively evaluating and comparing the bone mineral density (BMD) change between CHB- infected adolescents 12 to < 18 years of age treated with Tenofovir DF.
• Outcomes:
  The identification of bone AEs occurring in subjects taking Tenofovir DF between Baseline and Week 96 of treatment including the identification of ≥ 4% reduction in BMD within subjects and between monitoring groups from Baseline. Documentation of renal or bone AEs and outcomes among subjects receiving Tenofovir DF, including time to medication withdrawal or discontinuation.Subjects’ cumulative exposure time on Tenofovir DF at the time renal or bone AEs are detected up to and including Week 96 or to study discontinuation.
• Data analysis plan:
  All individual subject data will be listed as measured. All statistical summaries and analyses will be performed using SAS® software or other standard software tools including the STATA software. An efficacy analysis will be conducted after the last assigned subject reaches Week 96. The analysis will evaluate the difference in the proportion of subjects (Group 1 and 2 data will be pooled, as subjects have exposure to a single mode of therapy) achieving a composite endpoint of HBV DNA  400 copies/mL and ALT normal at Week 96, using a two-sided Fisher exact test with a non-completer equals failure approach.