Utilization and Efficacy of Tenofovir DF in Adolescents With Chronic Hepatitis B Virus Infection

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

The primary objective of this study is to characterize the long term (ie, 96 weeks of follow up) bone safety profile of open-label tenofovir disoproxil fumarate (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 in European treatment centers who are assigned to one of two schedules for renal and bone laboratory monitoring and BMD measurement.

Study Overview

• Status: Terminated
• Conditions: Hepatitis B
• Intervention / Treatment: Drug: Tenofovir DF; Radiation: DEXA Scan

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Cliniques Universitaries Saint- Luc, Departem Pediatrie
• France
  • Bron, France, 69677
    • Hopital Femmes Meres Enfants
• Greece
  • Chaidari, Greece, 12462
    • Attikon General Hospital of Athens
• Italy
  • Bologna, Italy, 40138
    • Azienda Ospedaliero-Universitaria di Bologna
• Romania
  • Bucharest, Romania, 11743
    • Grigore Alexandrescu Childrens Emergency Clinical Hospital
  • Constanta, Romania, 900708
    • Spitatul Clinic de Boli Infectioase Constanta
  • Iaşi, Romania, 700111
    • Institutul de Gastrenterologie si Hepatologie Iasi
• Spain
  • Barcelona, Spain, 8950
    • Hospital Sant Joan de Déu
  • Vigo, Spain, 36200
    • Hospital de Meixoeiro
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol
• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • Birmingham Children's Hospital NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

1. 12 to <16 years of age
2. Documented chronic hepatitis B virus (HBV) infection
3. Weight ≥ 35 kg
4. Able to swallow oral tablets
5. Negative pregnancy test for females of childbearing potential
6. Adequate kidney (renal) function
7. Parent or legal guardian of potential study subjects able to provide written informed consent

Key Exclusion Criteria:

1. Previously received tenofovir DF
2. Sexually-active males or females of reproductive potential who are not willing to use an effective method of contraception during the study
3. Females who are pregnant or breastfeeding, or females who wish to become pregnant during the course of the study
4. Known hypersensitivity to tenofovir DF, the metabolites or formulation excipients
5. Any condition (including alcohol or substance abuse) or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with treatment requirements

Note: Other protocol defined Inclusion/Exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Tenofovir DF + increased bone/renal monitoring; Participants will receive tenofovir DF, plus laboratory bone biomarker testing and lumbar spine and whole-body DEXA scans every 24 weeks from baseline to Week 96 (5 scans), and monitoring of renal function at 4 and 12 weeks after baseline and every 12 weeks thereafter. With the exception of an enhanced monitoring protocol for bone and renal outcomes, participants will be managed according to local standards of care.	Drug: Tenofovir DF; 300 mg tablet administered orally once daily for up to 96 weeks; Other Names: Viread®; Radiation: DEXA Scan; Dual energy x-ray absorptiometry (DEXA) scans administered at protocol-specified time points
Other: Tenofovir DF + prespecified bone monitoring; Participants will receive tenofovir DF, plus laboratory bone biomarker testing and lumbar spine and whole-body DEXA scans at baseline, Week 48, and Week 96. With the exception of pre-specified bone monitoring, participants will be managed according to local standards of care.	Drug: Tenofovir DF; 300 mg tablet administered orally once daily for up to 96 weeks; Other Names: Viread®; Radiation: DEXA Scan; Dual energy x-ray absorptiometry (DEXA) scans administered at protocol-specified time points

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants With Bone-Related Adverse Events and/or a ≥ 4% Reduction in Bone Mineral Density (BMD) From Baseline to Week 96	Baseline to Week 96

Collaborators and Investigators

• Sponsor: Gilead Sciences

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2015
• Primary Completion (Actual): February 28, 2018
• Study Completion (Actual): April 11, 2018

Study Registration Dates

• First Submitted: June 17, 2015
• First Submitted That Met QC Criteria: June 23, 2015
• First Posted (Estimate): June 24, 2015

Study Record Updates

• Last Update Posted (Actual): May 20, 2019
• Last Update Submitted That Met QC Criteria: February 21, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir
• Other Study ID Numbers: GS-EU-174-1403; 2014-004939-39 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No