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
- 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 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.
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: 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 (62)
Auckland Clinical Studies Limited
🇳🇿Auckland, New Zealand
Spitalul Grigore Alexandrescu-Sectia Pediatrie III
🇷🇴Bucharest, Romania
Institutul National de Boli Infectioase "Prof.Dr. Matei Bals"
🇷🇴Bucharest, Romania
Krasnoyarsk Regional Clinical Center of Maternal and Child Welfare
🇷🇺Krasnoyarsk, Russian Federation
Federal Budgetary Institution of Science "Central Scientific-Research Institute of Epidemiology"
🇷🇺Moscow, Russian Federation
Federal Research Centre of Nutrition, Biotechnology and Food Safety
🇷🇺Moscow, Russian Federation
Scientific Center of Children's Health of the Ministry of Health of the Russian Federation
🇷🇺Moscow, Russian Federation
Federal State-Financed Institution Pediatric Research and Clinical Center for Infectious Diseases
🇷🇺Saint-Petersburg, Russian Federation
Federal Budgetary Scientific Institution Pasteur St. Petersburg Scientific Research Institute of Epidemiology and Microbiology
🇷🇺Saint-Petersburg, Russian Federation
Republican Clinical Hospital of Infectious Diseases named after A.F. Agafonov
🇷🇺Tatarstan, Russian Federation
Limited Medical Company Hepatolog
🇷🇺Tolyatti, Russian Federation
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung City, Taiwan
Chang Gung Medical Foundation, Kaohsiung Chang Gung Memorial Hospital
🇨🇳Kaohsiung, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Taipei Mackay Memorial Hospital
🇨🇳Taipei, Taiwan
Chang Gung Medical Foundation, Chang Gung Memorial Hospital, Linkou
🇨🇳Taoyuan, Taiwan
Children's Hospital of Los Angeles
🇺🇸Los Angeles, California, United States
University of Miami/Schiff Center for Liver Diseases
🇺🇸Miami, Florida, United States
Rady Childrens Hospital
🇺🇸San Diego, California, United States
AdventHealth Medical Group
🇺🇸Orlando, Florida, United States
Children's Healthcare of Atlanta
🇺🇸Atlanta, Georgia, United States
Indiana University School of Medicine
🇺🇸Indianapolis, Indiana, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
University of California, San Francisco (UCSF)
🇺🇸San Francisco, California, United States
Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
University of Minnesota Masonic Children's Hospital
🇺🇸Minneapolis, Minnesota, United States
Children's Hospital & Medical Center
🇺🇸Omaha, Nebraska, 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
Monroe Carell Jr. Children's Hospital at Vanderbilt
🇺🇸Nashville, Tennessee, United States
Children's Medical Center
🇺🇸Dallas, Texas, United States
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Texas Children's Hospital - Main Hospital
🇺🇸Houston, Texas, United States
American Research Corporation at Texas Liver Institute
🇺🇸San Antonio, Texas, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
West Virginia University Hospitals
🇺🇸Morgantown, West Virginia, United States
Cliniques Universitaires Saint-LUC UCL
🇧🇪Brussels, Belgium
The Hospital for Sick Children
🇨🇦Toronto, Canada
BC Children's Hospital
🇨🇦Vancouver, Canada
GCS Medical Hospital & Research Center
🇮🇳Ahmedabad, India
SR Kalla Memorial Gastro And General Hospital
🇮🇳Jaipur, India
Pratha Gastro Liver Center
🇮🇳Kanpur, India
Prince of Wales Hospital
🇭🇰Shatin, Hong Kong
Institute of Post Graduation Medical Education & Research
🇮🇳Kolkata, India
M. V Hospital and Research Center
🇮🇳Lucknow, India
Seth GS Medical College and KEM Hospital
🇮🇳Mumbai, India
LTMMC & LTMG Hospital
🇮🇳Mumbai, India
Nandita Hospital and Research Centre
🇮🇳Nagpur, India
Khalatkar Hospital
🇮🇳Nagpur, India
Midas Multispecility Hospital PVT. LTD.
🇮🇳Nagpur, India
All India Institute of Medical Sciences
🇮🇳New Delhi, India
SIDS Hospital and Research Centre
🇮🇳Surat, India
Samvedna Hospital
🇮🇳Varanasi, India
AOU di Bologna - Policlinico S. Orsola Malpighi - Dipartimento Malattic dell'Apparato Digerente e Medicina Intema
🇮🇹Bologna, Italy
Kyungpook National University Hospital
🇰🇷Daegu, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of