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

Gilead Sciences

Status and phase: Active, not recruiting; Phase 2

Conditions: Chronic Hepatitis B

Treatments: Drug: TAF; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02932150

GS-US-320-1092

2016-000785-37 (EudraCT Number)

2023-506143-42 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 150 estimated patients

Sex: All

Ages: 2 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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150 participants in 7 patient groups, including a placebo group

TAF (Cohort 1)

Experimental group

Description:

Participants (12 to \< 18 years) weighing ≥ 35 kg will receive TAF 25 mg tablet for 24 weeks

Treatment:

Drug: TAF

Placebo (Cohort 1)

Placebo Comparator group

Description:

Participants (12 to \< 18 years) weighing ≥ 35 kg will receive placebo tablet for 24 weeks

Treatment:

Drug: Placebo

TAF (Cohort 2 Group 1)

Experimental group

Description:

Participants (6 to \< 12 years) weighing ≥ 25 kg will receive TAF 25 mg tablet for 24 weeks

Treatment:

Drug: TAF

TAF (Cohort 2 Group 2)

Experimental group

Description:

Participants (6 to \< 12 years) weighing ≥ 14 kg to \< 25 kg will receive TAF 15 mg oral granules for 24 weeks

Treatment:

Drug: TAF

TAF (Cohort 2 Group 3)

Experimental group

Description:

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)

Treatment:

Drug: TAF

Cohort 2 Placebo

Placebo Comparator group

Description:

Participants will receive matching placebo of TAF (tablet or oral granules) for 24 weeks.

Treatment:

Drug: Placebo

Open-Label TAF

Experimental group

Description:

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.

Treatment:

Drug: TAF