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

Phase 2RecruitingNCT02932150

Gilead Sciences150 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

150

Conditions

Chronic Hepatitis B

Interventions

TAFDRUG

Administered orally once daily

PlaceboDRUG

Administered orally once daily

Eligibility

Sex: ALLMin age: 2 YearsMax age: 17 Years

Medical Language ↔ Plain English

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.

Locations (62)

Outcomes

Primary Outcomes

Incidence of Treatment-Emergent Serious Adverse Events (SAEs) at Week 24

Time frame: Week 24

Incidence of Treatment-Emergent Adverse Events (AEs) at Week 24

Time frame: Week 24

Percentage of participants with plasma HBV DNA < 20 IU/mL at Week 24

Time frame: 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).

Time frame: Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 or 12

Secondary Outcomes

Percentage of participants experiencing graded laboratory abnormalities

Time frame: Weeks 24, 48, 96, and 240

Development as measured by Tanner Stage Assessment

Time frame: 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)

Time frame: Baseline; Weeks 24, 48, 96, and 240

Percentage change from baseline in BMD of lumbar spine by DXA

Time frame: Baseline; Weeks 24, 48, 96, and 240

Change from baseline in serum creatinine

Time frame: Baseline; Weeks 4, 8, 12, 24, 48, 96, and 240

Change from baseline in estimated glomerular filtration rate (eGFR) by the Schwartz formula

Central Contacts

Gilead Study Team

CONTACT

GS-US-320-1092@gilead.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Children's Hospital of Los Angeles

Los Angeles, California, United States

RECRUITING

Rady Childrens Hospital

San Diego, California, United States

RECRUITING

University of California, San Francisco (UCSF)

San Francisco, California, United States

ACTIVE_NOT_RECRUITING

Children's Hospital Colorado

Aurora, Colorado, United States

ACTIVE_NOT_RECRUITING

University of Miami/Schiff Center for Liver Diseases

Miami, Florida, United States

WITHDRAWN

AdventHealth Medical Group

Orlando, Florida, United States

WITHDRAWN

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

WITHDRAWN

Indiana University School of Medicine

Indianapolis, Indiana, United States

RECRUITING

Johns Hopkins University

Baltimore, Maryland, United States

RECRUITING

University of Minnesota Masonic Children's Hospital

Minneapolis, Minnesota, United States

WITHDRAWN

...and 52 more locations

Time frame: 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

Time frame: 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

Time frame: Weeks 48, 96, and 240

Change from baseline in retinol-binding protein to creatine ratio at Weeks 4, 8, 12, 24, and 48

Time frame: 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

Time frame: Baseline; Weeks 4, 8, 12, 24, and 48

Change from baseline in glucose at Weeks 4, 8, 12, 24, and 48

Time frame: Baseline; Weeks 4, 8, 12, 24, and 48

Change from baseline in phosphate at Weeks 4, 8, 12, 24, and 48

Time frame: Baseline; Weeks 4, 8, 12, 24, and 48

Percentage of participants with plasma HBV DNA < 20 IU/mL at Weeks 48, 96, and 240

Time frame: 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

Time frame: Weeks 24, 48, 96, and 240

Percentage of participants with alanine aminotransferase (ALT) normalization at Weeks 24, 48, 96, and 240

Time frame: 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

Time frame: Weeks 24, 48, 96 and 240

Change from baseline in fibrosis as assessed by FibroTest at Weeks 24, 48, 96, and 240

Time frame: 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

Time frame: 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)

Time frame: 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)

Time frame: 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

Time frame: Weeks 24, 48, 96, and 240

Percentage of participants with qHBsAg log10 IU/mL at Weeks 24, 48, 96, and 240

Time frame: Weeks 24, 48, 96, and 240

Incidence of resistance mutations at Weeks 24, 48, 96, and 240

Time frame: 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).

Time frame: 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).

Time frame: 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).