Study of Tenofovir Alafenamide (TAF) in Children and Teen Participants With Chronic Hepatitis B Virus Infection
- Registration Number
- NCT02932150
- Lead Sponsor
- Gilead Sciences
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 150
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Open-Label TAF 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. TAF (Cohort 1) TAF Participants (12 to \< 18 years) weighing ≥ 35 kg will receive TAF 25 mg tablet for 24 weeks Placebo (Cohort 1) Placebo Participants (12 to \< 18 years) weighing ≥ 35 kg will receive placebo tablet for 24 weeks TAF (Cohort 2 Group 1) TAF Participants (6 to \< 12 years) weighing ≥ 25 kg will receive TAF 25 mg tablet for 24 weeks TAF (Cohort 2 Group 3) TAF 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) Cohort 2 Placebo Placebo Participants will receive matching placebo of TAF (tablet or oral granules) for 24 weeks. TAF (Cohort 2 Group 2) TAF Participants (6 to \< 12 years) weighing ≥ 14 kg to \< 25 kg will receive TAF 15 mg oral granules for 24 weeks
- Primary Outcome Measures
Name Time Method 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 Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 or 12 AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Incidence of Treatment-Emergent Serious Adverse Events (SAEs) at Week 24 Week 24
- Secondary Outcome Measures
Name Time Method 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 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 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 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 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 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 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 Change from baseline in estimated glomerular filtration rate (eGFR) by the Schwartz formula Baseline; 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 Baseline; Weeks 4, 24, and 36 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).
Palatability of study drug Baseline; Weeks 4, 24, and 36 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).
PK Parameter: AUCtau of tenofovir (TFV) 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) AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
PK Parameter: AUClast of TAF and TFV 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) AUClast is defined as the concentration of drug from time zero to the last observable concentration.
PK Parameter: Ctau of TFV 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) Ctau is defined as the observed drug concentration at the end of the dosing interval.
PK Parameter: Cmax of TAF and TFV 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) Cmax is defined as the maximum observed concentration of drug.
PK Parameter: Clast of TAF and TFV 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) Clast is defined as the last observable concentration of drug.
PK Parameter: Tmax of TAF and TFV 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) Tmax is defined as the time of Cmax (the maximum concentration of drug).
PK Parameter: Tlast of TAF and TFV 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) Tlast is defined as the time (observed time point) of Clast.
PK Parameter: λz of TAF and TFV 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) 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.
PK Parameter: CL/F of TAF and TFV 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) CL/F is defined as the apparent oral clearance following administration of the drug.
PK Parameter: Vz/F of TAF and TFV 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) Vz/F is defined as the apparent volume of distribution of the drug.
PK Parameter: t1/2 of TAF and TFV 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) t1/2 is defined as the estimate of the terminal elimination half-life of the drug.
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 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 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 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
Trial Locations
- Locations (39)
Children's Hospital of Los Angeles
🇺🇸Los Angeles, California, United States
Rady Childrens Hospital
🇺🇸San Diego, California, United States
University of California, San Francisco (UCSF)
🇺🇸San Francisco, California, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Indiana University School of Medicine
🇺🇸Indianapolis, Indiana, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
The Children's Hospital at Montefiore
🇺🇸Bronx, New York, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Scroll for more (29 remaining)Children's Hospital of Los Angeles🇺🇸Los Angeles, California, United States