Study to Evaluate the Antiviral Efficacy, Safety and Tolerability of Tenofovir Disoproxil Fumarate Versus Placebo in Pediatric Participants With Chronic Hepatitis B Infection

A Randomized, Double-Blind Evaluation of the Antiviral Efficacy, Safety, and Tolerability of Tenofovir Disoproxil Fumarate Versus Placebo in Pediatric Patients With Chronic Hepatitis B Infection

The primary objective of this study is to evaluate the antiviral efficacy of tenofovir disoproxil fumarate (tenofovir DF; TDF) versus placebo in pediatric population (aged 2 to < 12 years at the time of enrollment) with chronic hepatitis B (CHB) infection.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: Tenofovir DF; Drug: TDF Placebo

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • Bangalore, India, 560034
    • St. John Hospital & Medical Center
  • Gujarat
    • Surat, Gujarat, India, 395 002
      • Nirmal Hospital Private Limited
  • Haryana
    • Gurgaon, Haryana, India, 122 001
      • Medanta -The Medicity
  • Maharashtra
    • Nagpur, Maharashtra, India, 440012
      • Colors Children Hospital
  • Rajasthan
    • Jaipur, Rajasthan, India, 302004
      • SMS Medical College and Hospital
  • Uttar Pradesh
    • Lucknow, Uttar Pradesh, India, 226003
      • M.V. Hospital and Research Centre 314/30 Mirza Mandi Chowk
• Romania
  • Bucharest, Romania, 011743
    • Grigore Alexandrescu Emergency Clinical Hospital for Children
  • Bucharest, Romania, 022328
    • Fundeni Clinical Institute - Constantinesco
  • Craiova, Romania, 200515
    • Victor Babes Clinical Hospital of Infectious Diseases and Pneumophtisology
• South Korea
  • Daegu, South Korea, 41944
    • Kyungpook National University
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 120-752
    • Severance Children's Hospital
  • Gyeongsangnam-do
    • Yangsan, Gyeongsangnam-do, South Korea, 50612
      • Pusan National University Yangsan Hospital
• Taiwan
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 11 years (Child)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Male or Female, 2 to < 12 years of age
• Weight ≥ 10 kg
• Chronic HBV infection ≥ 6 months
• Hepatitis B e antigen (HBeAg)-positive or HBeAg-negative
• HBV Viral Load ≥ 100,000 copies/mL
• Alanine aminotransferase (ALT) ≥ 1.5 x the upper limit of the normal range (ULN) at screening
• Creatinine Clearance ≥ 80 mL/min/1.73m^2
• Absolute neutrophil count (ANC) ≥ 1,500/mm^3, hemoglobin ≥ 10 g/dL
• Negative pregnancy test at screening
• No prior tenofovir DF therapy (participants may have received prior interferon-alfa and/or other oral anti-HBV nucleoside/nucleotide therapy; participants must have discontinued interferon-alfa therapy ≥ 6 months prior to screening; participants 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)

Key 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 > 50 ng/mL
• Evidence of hepatocellular carcinoma (HCC)
• Co-infection with human immunodeficiency virus (HIV), acute hepatitis A virus (HAV), hepatitis C virus (HCV), or hepatitis D virus (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

Note: Other protocol defined Inclusion/Exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tenofovir DF (Blinded Randomized Treatment); Participants will receive tenofovir disoproxil fumarate (tenofovir DF; TDF) for 72 weeks (protocol amendment 2) or 48 weeks (protocol amendment 3).	Drug: Tenofovir DF; Participants weighing ≥ 17 kg will receive TDF one tablet administered orally once daily (150, 200, 250 or 300 mg tablets based on body weight).; Participants weighing < 17 kg or ≥ 17 kg who are unable to swallow a tablet will receive TDF oral powder in a dose of 8 mg/kg once daily up to a maximum dose of 300 mg.; Other Names: Viread®
Placebo Comparator: Placebo to match TDF (Blinded Randomized Treatment); Participants will receive TDF placebo for 72 weeks (protocol amendment 2) or 48 weeks (protocol amendment 3).	Drug: TDF Placebo; Participants weighing ≥ 17 kg will receive TDF placebo tablet administered orally once daily.; Participants weighing < 17 kg or ≥ 17 kg who are unable to swallow a tablet will receive TDF placebo oral powder once daily.
Experimental: Tenofovir DF (Open-label Treatment); Following 72 weeks (protocol amendment 2) or 48 weeks (protocol amendment 3) of blinded randomized treatment, participants will switch to open-label TDF treatment for an additional 120 weeks (protocol amendment 2) or 144 weeks (protocol amendment 3).	Drug: Tenofovir DF; Participants weighing ≥ 17 kg will receive TDF one tablet administered orally once daily (150, 200, 250 or 300 mg tablets based on body weight).; Participants weighing < 17 kg or ≥ 17 kg who are unable to swallow a tablet will receive TDF oral powder in a dose of 8 mg/kg once daily up to a maximum dose of 300 mg.; Other Names: Viread®
Experimental: Tenofovir DF (Open-label Extension Phase); Following the completion of study at Week 192, participants may have the option to receive open-label TDF until it is commercially available in that country for treatment of chronic HBV in participants of their age and weight.	Drug: Tenofovir DF; Participants weighing ≥ 17 kg will receive TDF one tablet administered orally once daily (150, 200, 250 or 300 mg tablets based on body weight).; Participants weighing < 17 kg or ≥ 17 kg who are unable to swallow a tablet will receive TDF oral powder in a dose of 8 mg/kg once daily up to a maximum dose of 300 mg.; Other Names: Viread®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants With Serum HBV DNA < 400 Copies/mL (69 IU/mL) at Week 48 (Missing = Failure Approach)	Week 48
Percentage of Participants With Serum HBV DNA < 400 Copies/mL (69 IU/mL) at Week 48 (Missing = Excluded Approach)	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Seroconversion at Week 48	HBeAg seroconversion was defined as HBeAg loss and a change from HBeAb negative or missing at baseline to HBeAb positive.	Week 48
Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Week 48, Based on the American Association for the Study of Liver Diseases (AASLD) Normal Range	Normal ALT was defined as ≤ 30 U/L for males and females 0-12 years based on the AASLD pediatric normal range.	Week 48
Percentage of Participants With Normal ALT at Week 192, Based on the AASLD Normal Range	Normal ALT was defined as ≤ 30 U/L for males and females 0-12 years based on the AASLD pediatric normal range.	Week 192
Percentage of Participants With Normal ALT at Week 48, Based on the Central Lab Normal Range	Normal ALT was defined as ≤ 34 U/L for females aged 2-15 years old or males aged 1-9 years old, and ≤ 43 U/L for males aged 10-15 years old based on the central lab normal range.	Week 48
Percentage of Participants With Normal ALT at Week 192, Based on the Central Lab Normal Range	Normal ALT was defined as ≤ 34 U/L for females aged 2-15 years old or males aged 1-9 years old, and ≤ 43 U/L for males aged 10-15 years old based on the central lab normal range.	Week 192
Percentage of Participants With Normalized ALT at Week 48, Based on the AASLD Normal Range	Normal ALT was defined as ≤ 30 U/L for males and females 0-12 years based on the AASLD pediatric normal range. ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit.	Week 48
Percentage of Participants With Normalized ALT at Week 192, Based on the AASLD Normal Range	Normal ALT was defined as ≤ 30 U/L for males and females 0-12 years based on the AASLD pediatric normal range. ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit.	Week 192
Percentage of Participants With Normalized ALT at Week 48, Based on the Central Lab Normal Range	Normal ALT was defined as ≤ 34 U/L for females aged 2-15 years old or males aged 1-9 years old, and ≤ 43 U/L for males aged 10-15 years old based on the central lab normal range. ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit.	Week 48
Percentage of Participants With Normalized ALT at Week 192, Based on the Central Lab Normal Range	Normal ALT was defined as ≤ 34 U/L for females aged 2-15 years old or males aged 1-9 years old, and ≤ 43 U/L for males aged 10-15 years old based on the central lab normal range. ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit.	Week 192
Composite Endpoint of Percentage of Participants With HBV DNA < 400 Copies/mL (69 IU/mL) and Normalized ALT (Based on AASLD Normal Range) at Week 48	Normal ALT was defined as ≤ 30 U/L for males and females 0-12 years based on the AASLD pediatric normal range. ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit.	Week 48
Composite Endpoint of Percentage of Participants With HBV DNA < 400 Copies/mL (69 IU/mL) and Normalized ALT (Based on AASLD Normal Range) at Week 192	Normal ALT was defined as ≤ 30 U/L for males and females 0-12 years based on the AASLD pediatric normal range. ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit.	Week 192
Composite Endpoint of Percentage of Participants With HBV DNA < 400 Copies/mL (69 IU/mL) and Normalized ALT (Based on Central Lab Normal Range) at Week 48	Normal ALT was defined as ≤ 34 U/L for females aged 2-15 years old or males aged 1-9 years old, and ≤ 43 U/L for males aged 10-15 years old based on the central lab normal range. ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit.	Week 48
Composite Endpoint of Percentage of Participants With HBV DNA < 400 Copies/mL (69 IU/mL) and Normalized ALT (Based on Central Lab Normal Range) at Week 192	Normal ALT was defined as ≤ 34 U/L for females aged 2-15 years old or males aged 1-9 years old, and ≤ 43 U/L for males aged 10-15 years old based on the central lab normal range. ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit.	Week 192
Percentage of Participants With HBV DNA < 169 Copies/mL (29 IU/mL) at Week 48		Week 48
Percentage of Participants With HBV DNA < 169 Copies/mL (29 IU/mL) at Week 192		Week 192
Percentage of Participants With HBsAg Loss at Week 48	HBsAg Loss was defined as a change from HBsAg positive or missing at baseline to HBsAg negative.	Week 48
Percentage of Participants With HBsAg Loss at Week 192	HBsAg Loss was defined as a change from HBsAg positive or missing at baseline to HBsAg negative.	Week 192
Percentage of Participants With HBsAg Seroconversion at Week 48	HBsAg seroconversion was defined as HBsAg loss and a change from HBsAb negative or missing at baseline to HBsAb positive.	Week 48
Percentage of Participants With HBsAg Seroconversion at Week 192	HBsAg seroconversion was defined as HBsAg loss and a change from HBsAb negative or missing at baseline to HBsAb positive.	Week 192
Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase for Participants Who Were Viremic (HBV DNA ≥ 400 Copies/mL [69 IU/mL]) Including Participants With Confirmed Virologic Breakthrough at Week 48		Baseline; Week 48
Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase for Participants Who Were Viremic (HBV DNA ≥ 400 Copies/mL [69 IU/mL]) Including Participants With Confirmed Virologic Breakthrough at Week 96		Baseline; Week 96
Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase for Participants Who Were Viremic (HBV DNA ≥ 400 Copies/mL [69 IU/mL]) Including Participants With Confirmed Virologic Breakthrough at Week 144		Baseline; Week 144
Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase for Participants Who Were Viremic (HBV DNA ≥ 400 Copies/mL [69 IU/mL]) Including Participants With Confirmed Virologic Breakthrough at Week 192		Baseline; Week 192
Percentage of Participants With ≥ 4% Decrease From Baseline in Spine Bone Mineral Density (BMD) at Week 48		Baseline; Week 48
Percentage of Participants With ≥ 4% Decrease From Baseline in Spine BMD at Week 192		Baseline; Week 192
Percent Change From Baseline in BMD of Spine at Week 48		Baseline; Week 48
Percent Change From Baseline in BMD of Spine at Week 192		Baseline; Week 192

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

General Publications

• (Oral Presentation) Mei-Hwei Chang, Jae Hong Park, Jorge A. Bezerra, Daniela Pacura, Sandeep Nijhawan, Byung-Ho Choe, et al. Randomized, Double-Blind, Placebo-Controlled Trial of Tenofovir Disoproxil Fumarate (TDF) in Children with Chronic Hepatitis B (CHB). Hepatology, 2018; 68 (Suppl 1): 49A.

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2012
• Primary Completion (Actual): August 7, 2017
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: July 25, 2012
• First Submitted That Met QC Criteria: July 25, 2012
• First Posted (Estimated): July 27, 2012

Study Record Updates

• Last Update Posted (Actual): January 30, 2026
• Last Update Submitted That Met QC Criteria: January 14, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Pathologic Processes; Chronic Disease; Disease Attributes; Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Communicable Diseases; DNA Virus Infections; Hepadnaviridae Infections; Hepatitis, Chronic; Hepatitis; Pathological Conditions, Signs and Symptoms; Hepatitis B; Hepatitis B, Chronic; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Purines; Organophosphorus Compounds; Organophosphonates; Adenine; Tenofovir
• Other Study ID Numbers: GS-US-174-0144; 2012-000586-20 (EudraCT Number); 2024-517526-26 (Other Identifier: CTIS Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No