Purpose

The primary objective of Cohort 1 of this study is to evaluate the safety, tolerability, and antiviral activity (HBV DNA < 20 IU/mL) of tenofovir alafenamide (TAF) 25 mg once daily versus placebo through Week 24 in treatment-naive and treatment-experienced adolescents (aged 12 to < 18 years) with chronic hepatitis B (CHB). Cohort 2 will consist of 2 parts: Part A and Part B. Intensive pharmacokinetic (PK) data will be collected from all participants in Part A to confirm the dose of TAF in each dose group and the remaining participants will be enrolled into Part B once dose confirmation is achieved. The primary objectives of Part A are to evaluate the steady-state PK of TAF and tenofovir (TFV) and confirm the dose of TAF given once daily in children (aged 2 to < 12 years) with CHB. The primary objective of Part B is to evaluate the safety and tolerability of TAF at Week 48 and the antiviral activity (HBV DNA < 20 IU/mL) of TAF at Week 24 in children (aged 2 to < 12 years) with CHB.

Condition

Eligibility

Eligible Ages
Between 2 Years and 17 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 = ≥ 17 kg to < 25 kg (≥ 37 lbs to <55 lbs)
  • Cohort 2 Group 3 = < 17 kg (< 37 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)
  • 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

Exclusion Criteria

  • Females who are 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 Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
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 ≥ 17 kg to < 25 kg will receive TAF 15 mg tablet for 24 weeks
  • Drug: TAF
    Administered orally once daily
Experimental
TAF (Cohort 2 Group 3)
Participants (2 to < 6 years) weighing < 17 kg who are unable to swallow a tablet will receive oral granules of TAF (dose to be determined) for 24 weeks.
  • Drug: TAF
    Administered orally once daily
Experimental
TAF (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

Recruiting Locations

Nashville, Tennessee 37232

More Details

NCT ID
NCT02932150
Status
Recruiting
Sponsor
Gilead Sciences

Study Contact

Gilead Study Team
GS-US-320-1092@gilead.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.