Study of Tenofovir Alafenamide (TAF) in Children and Teen Participants With Chronic Hepatitis B Virus Infection

A Randomized, Double-Blind Evaluation of the Pharmacokinetics, Safety, and Antiviral Efficacy of Tenofovir Alafenamide (TAF) in Children and Adolescent Subjects With Chronic Hepatitis B Virus Infection

The goals of this clinical study are to compare the effectiveness, safety and tolerability of study drug, tenofovir alafenamide (TAF), versus placebo in teens and children with CHB and to learn more about the dosing levels in children.

Study Overview

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

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint-Luc UCL
• Hong Kong
  • Shatin, Hong Kong
    • Prince of Wales Hospital
• India
  • Kolkata, India, 700020
    • Institute of Post Graduation Medical Education & Research
  • Lucknow, India, 226003
    • M. V Hospital and Research Center
  • Mumbai, India, 400012
    • Seth GS medical college and KEM Hospital
  • Mumbai, India, 400022
    • LTMMC & LTMG Hospital
  • Nagpur, India, 440009
    • Khalatkar Hospital
  • New Delhi, India, 110029
    • All India Institute of Medical Sciences
  • Surat, India, 395002
    • SIDS Hospital and Research Centre
  • Varanasi, India, 221005
    • Samvedna Hospital
• Romania
  • Bucharest, Romania, 11743
    • Spitalul Grigore Alexandrescu-Sectia Pediatrie III
  • Bucharest, Romania, 21105
    • Institutul National de Boli Infectioase "Prof.Dr. Matei Bals"
• Russia
  • Moscow, Russia, 115446
    • Federal Research Centre of Nutrition, Biotechnology and Food Safety
  • Saint Petersburg, Russia, 197022
    • Federal State-Financed Institution Pediatric Research and Clinical Center for Infectious Diseases
  • Tatarstan, Russia, 420110
    • Republican Clinical Hospital of Infectious Diseases named after A.F. Agafonov
  • Tolyatti, Russia, 445009
    • Limited Medical Company Hepatolog
• South Korea
  • Daegu, South Korea, 41944
    • Kyungpook National University Hospital
  • Seoul, South Korea, 5505
    • Asan Medical Center
  • Seoul, South Korea, 6351
    • Samsung Medical Center
• Taiwan
  • Kaohsiung City, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Kaohsiung City, Taiwan, 83301
    • Chang Gung Medical Foundation, Kaohsiung Chang Gung Memorial Hospital
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taoyuan, Taiwan, 33305
    • Chang Gung Medical Foundation, Chang Gung Memorial Hospital, Linkou
• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital of Los Angeles
    • San Diego, California, United States, 92123
      • Rady Childrens Hospital
    • San Francisco, California, United States, 94158
      • University of California, San Francisco (UCSF)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
  • New York
    • The Bronx, New York, United States, 10467
      • The Children's Hospital at Montefiore
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Monroe Carell Jr. Children's Hospital at Vanderbilt
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital - Main Hospital
    • San Antonio, Texas, United States, 78215
      • American Research Corporation at Texas Liver Institute
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Key Inclusion criteria:

• Males and non-pregnant, non-lactating females

• Weight at screening as follows:

  • Cohort 1 = ≥ 35 kg (≥ 77 lbs)
  • Cohort 2 Group 1 = ≥ 25 kg (≥ 55 lbs)
  • Cohort 2 Group 2 = ≥ 14 kg to < 25 kg (≥ 30 lbs to <55 lbs)

  • Cohort 2 Group 3 = ≥ 10 kg to < 14 kg (≥ 22 lbs to < 30 lbs) or

    • 14 kg to < 25 kg (≥ 30 lbs to < 55 lbs)
• Willing and able to provide written informed consent/assent (child and parent/legal guardian)
• Documented evidence of CHB (eg, HBsAg-positive for ≥ 6 months)

• HBeAg-positive, or HBeAg-negative, chronic HBV infection with all of the following:

  • Screening HBV DNA ≥ 2 × 10^4 IU/mL
  • Screening serum ALT > 45 U/L (> 1.5 × ULN: 30 U/L) and ≤ 10 × ULN (by central laboratory range)
• Treatment-naive or treatment-experienced will be eligible for enrollment.
• Estimated creatinine clearance (CLCr) ≥ 80 mL/min/1.73m^2 (using the Schwartz formula)
• Normal ECG

Key Exclusion criteria:

• Females who are pregnant or breastfeeding
• Males and females of reproductive potential who are unwilling to use an "effective", protocol-specified method(s) of contraception during the study.
• Coinfection with hepatitis C virus (HCV), HIV, or hepatitis D virus (HDV)
• Evidence of hepatocellular carcinoma (Note: if screening alpha-fetoprotein (AFP) is < 50 ng/mL no imaging study is needed; however, if the screening AFP is > 50 ng/mL an imaging study is required)
• Any history of, or current evidence of, clinical hepatic decompensation
• Abnormal hematological and biochemical parameters
• Chronic liver disease of non-HBV etiology (e.g., hemochromatosis, alpha-1 antitrypsin deficiency, cholangitis)
• Received solid organ or bone marrow transplant
• Currently receiving therapy with immunomodulators (eg, corticosteroids), or immunosuppressants
• Significant renal, cardiovascular, pulmonary, or neurological disease in the opinion of the Investigator
• Malignancy within the 5 years prior to screening. Individuals under evaluation for possible malignancy are not eligible.
• Current alcohol or substance abuse judged by the investigator to potentially interfere with subject compliance.

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: Double

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TAF (Cohort 1); Participants (12 to < 18 years) weighing ≥ 35 kg will receive TAF 25 mg tablet for 24 weeks	Drug: TAF; Administered orally once daily
Placebo Comparator: Placebo (Cohort 1); Participants (12 to < 18 years) weighing ≥ 35 kg will receive placebo tablet for 24 weeks	Drug: Placebo; Administered orally once daily
Experimental: TAF (Cohort 2 Group 1); Participants (6 to < 12 years) weighing ≥ 25 kg will receive TAF 25 mg tablet for 24 weeks	Drug: TAF; Administered orally once daily
Experimental: TAF (Cohort 2 Group 2); Participants (6 to < 12 years) weighing ≥ 14 kg to < 25 kg will receive TAF 15 mg oral granules for 24 weeks	Drug: TAF; Administered orally once daily
Placebo Comparator: Cohort 2 Placebo; Participants will receive matching placebo of TAF (tablet or oral granules) for 24 weeks.	Drug: Placebo; Administered orally once daily
Experimental: Open-Label TAF; Following 24 weeks of blinded randomized treatment, participants will be eligible to participate in an open-label extension phase to receive TAF for an additional 216 weeks.	Drug: TAF; Administered orally once daily
Experimental: TAF (Cohort 2 Group 3); Participants (2 to < 6 years) will receive TAF for 24 weeks as follows: weight ≥ 10 kg to < 14 kg (7.5 mg oral granules); weight ≥ 14 kg to < 25 kg (15 mg oral granules) The study has reopened and recruitment is initiated only for this cohort for ≥ 10 to < 14 kg at this time.	Drug: TAF; Administered orally once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Serious Adverse Events (SAEs) at Week 24		Week 24
Incidence of Treatment-Emergent Adverse Events (AEs) at Week 24		Week 24
Percentage of participants with plasma HBV DNA < 20 IU/mL at Week 24		Week 24
PK Parameter: AUCtau of TAF for participants from Cohort 2 Part A	AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).	Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 or 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants experiencing graded laboratory abnormalities		Weeks 24, 48, 96, and 240
Development as measured by Tanner Stage Assessment		Weeks 24, 48, 96, and 240
Percentage change from baseline in bone mineral density (BMD) of whole body (minus head) by dual imaging x-ray absorptiometry (DXA)		Baseline; Weeks 24, 48, 96, and 240
Percentage change from baseline in BMD of lumbar spine by DXA		Baseline; Weeks 24, 48, 96, and 240
Change from baseline in serum creatinine		Baseline; Weeks 4, 8, 12, 24, 48, 96, and 240
Change from baseline in estimated glomerular filtration rate (eGFR) by the Schwartz formula		Baseline; Weeks 24, 48, 96, and 240
Incidence of treatment-emergent SAEs in participants treated with TAF or placebo for 24 weeks followed by open-label TAF at Weeks 48, 96 and 240		Weeks 48, 96, and 240
Incidence of treatment-emergentAEs in participants treated with TAF or placebo for 24 weeks followed by open-label TAF at Weeks 48, 96 and 240		Weeks 48, 96, and 240
Change from baseline in retinol-binding protein to creatine ratio at Weeks 4, 8, 12, 24, and 48		Baseline; Weeks 4, 8, 12, 24, and 48
Change from baseline in beta-2-microglobulin to creatine ratio at Weeks 4, 8, 12, 24, and 48		Baseline; Weeks 4, 8, 12, 24, and 48
Change from baseline in glucose at Weeks 4, 8, 12, 24, and 48		Baseline; Weeks 4, 8, 12, 24, and 48
Change from baseline in phosphate at Weeks 4, 8, 12, 24, and 48		Baseline; Weeks 4, 8, 12, 24, and 48
Percentage of participants with plasma HBV DNA < 20 IU/mL at Weeks 48, 96, and 240		Weeks 48, 96, and 240
Proportion of participants with plasma HBV DNA < 20 IU/mL (target not detected) at Weeks 24, 48, 96, and 240		Weeks 24, 48, 96, and 240
Percentage of participants with alanine aminotransferase (ALT) normalization at Weeks 24, 48, 96, and 240		Weeks 24, 48, 96, and 240
Composite endpoint of percentage of participants with ALT normalization and HBV DNA < 20 IU/mL at Weeks 24, 48, 96 and 240		Weeks 24, 48, 96 and 240
Change from baseline in fibrosis as assessed by FibroTest at Weeks 24, 48, 96, and 240		Baseline; Weeks 24, 48, 96, and 240
Percentage of participants with hepatitis B e antigen (HBeAg) loss and seroconversion to anti-HBe (HBeAG-positive participants only) at Weeks 24, 48, 96, and 240		Weeks 24, 48, 96, and 240
Percentage of participants with composite endpoint of HBeAg seroconversion and HBV DNA < 20 IU/mL at Weeks 24, 48, 96, and 240 (in HBeAg-positive participants only)		Weeks 24, 48, 96, and 240
Percentage of participants with composite endpoint of ALT normalization, HBeAg seroconversion and HBV DNA < 20 IU/mL at Weeks 24, 48, 96, and 240 (in HBeAg-positive participants only)		Weeks 24, 48, 96, and 240
Percentage of participants with hepatitis B surface antigen (HBsAg) loss and seroconversion to anti-HBs at Weeks 24, 48, 96, and 240		Weeks 24, 48, 96, and 240
Percentage of participants with qHBsAg log10 IU/mL at Weeks 24, 48, 96, and 240		Weeks 24, 48, 96, and 240
Incidence of resistance mutations at Weeks 24, 48, 96, and 240		Weeks 24, 48, 96, and 240
Acceptability of study drug	To assess acceptability of study drug, the investigator will ask participants if they were able to taste the medication on a scale of 1-5, how much they like the taste of the medication (1 = dislike very much to 5 = like very much).	Baseline; Weeks 4, 24, and 36
Palatability of study drug	To assess palatability of study drug, the investigator will ask participants on a scale of 0-3 how easy it was to swallow the pill (0 = poor to 3 = excellent).	Baseline; Weeks 4, 24, and 36
PK Parameter: AUCtau of tenofovir (TFV)	AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).	Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 (Cohort 1), and Week 4, 8, or 12 (Cohort 2)
PK Parameter: AUClast of TAF and TFV	AUClast is defined as the concentration of drug from time zero to the last observable concentration.	Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 (Cohort 1), and Week 4, 8, or 12 (Cohort 2)
PK Parameter: Ctau of TFV	Ctau is defined as the observed drug concentration at the end of the dosing interval.	Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 (Cohort 1), and Week 4, 8, or 12 (Cohort 2)
PK Parameter: Cmax of TAF and TFV	Cmax is defined as the maximum observed concentration of drug.	Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 (Cohort 1), and Week 4, 8, or 12 (Cohort 2)
PK Parameter: Clast of TAF and TFV	Clast is defined as the last observable concentration of drug.	Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 (Cohort 1), and Week 4, 8, or 12 (Cohort 2)
PK Parameter: Tmax of TAF and TFV	Tmax is defined as the time of Cmax (the maximum concentration of drug).	Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 (Cohort 1), and Week 4, 8, or 12 (Cohort 2)
PK Parameter: Tlast of TAF and TFV	Tlast is defined as the time (observed time point) of Clast.	Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 (Cohort 1), and Week 4, 8, or 12 (Cohort 2)
PK Parameter: λz of TAF and TFV	λz is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug.	Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 (Cohort 1), and Week 4, 8, or 12 (Cohort 2)
PK Parameter: CL/F of TAF and TFV	CL/F is defined as the apparent oral clearance following administration of the drug.	Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 (Cohort 1), and Week 4, 8, or 12 (Cohort 2)
PK Parameter: Vz/F of TAF and TFV	Vz/F is defined as the apparent volume of distribution of the drug.	Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 (Cohort 1), and Week 4, 8, or 12 (Cohort 2)
PK Parameter: t1/2 of TAF and TFV	t1/2 is defined as the estimate of the terminal elimination half-life of the drug.	Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 (Cohort 1), and Week 4, 8, or 12 (Cohort 2)

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2016
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): October 1, 2029

Study Registration Dates

• First Submitted: September 16, 2016
• First Submitted That Met QC Criteria: October 11, 2016
• First Posted (Estimated): October 13, 2016

Study Record Updates

• Last Update Posted (Actual): June 18, 2026
• Last Update Submitted That Met QC Criteria: June 16, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: HBV; CHB
• 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
• Other Study ID Numbers: GS-US-320-1092; 2016-000785-37 (EudraCT Number); 2023-506143-42 (Other Identifier: European Medicines Agency)

Drug and device information, study documents

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