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

Chronic Hepatitis B Clinical Trial

Official title:

A Randomized, Double-Blind Evaluation of the Pharmacokinetics, Safety, and Antiviral Efficacy of Tenofovir Alafenamide (TAF) in Children and Adolescent Subjects With Chronic Hepatitis B Virus Infection

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02932150
• Other study ID #: GS-US-320-1092
• Secondary ID: 2016-000785-3720
• Status: Recruiting
• Phase: Phase 2
• Start date: November 2016
• Est. completion date: October 2029

Study information

• Verified date: June 2024
• Source: Gilead Sciences
• Contact: Gilead Study Team
• Email: GS-US-320-1092[@]gilead.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: October 2029
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic
• Herpesviridae Infections
• Virus Diseases

Intervention

Drug:
• TAF
Administered orally once daily
• Placebo
Administered orally once daily

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Hong Kong,  India,  Italy,  Korea, Republic of,  New Zealand,  Romania,  Russian Federation,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment-Emergent Serious Adverse Events (SAEs) at Week 24		Week 24
Primary	Incidence of Treatment-Emergent Adverse Events (AEs) at Week 24		Week 24
Primary	Percentage of participants with plasma HBV DNA < 20 IU/mL at Week 24		Week 24
Primary	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).	Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 or 12
Secondary	Percentage of participants experiencing graded laboratory abnormalities		Weeks 24, 48, 96, and 240
Secondary	Development as measured by Tanner Stage Assessment		Weeks 24, 48, 96, and 240
Secondary	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
Secondary	Percentage change from baseline in BMD of lumbar spine by DXA		Baseline; Weeks 24, 48, 96, and 240
Secondary	Change from baseline in serum creatinine		Baseline; Weeks 4, 8, 12, 24, 48, 96, and 240
Secondary	Change from baseline in estimated glomerular filtration rate (eGFR) by the Schwartz formula		Baseline; Weeks 24, 48, 96, and 240
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change from baseline in glucose at Weeks 4, 8, 12, 24, and 48		Baseline; Weeks 4, 8, 12, 24, and 48
Secondary	Change from baseline in phosphate at Weeks 4, 8, 12, 24, and 48		Baseline; Weeks 4, 8, 12, 24, and 48
Secondary	Percentage of participants with plasma HBV DNA < 20 IU/mL at Weeks 48, 96, and 240		Weeks 48, 96, and 240
Secondary	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
Secondary	Percentage of participants with alanine aminotransferase (ALT) normalization at Weeks 24, 48, 96, and 240		Weeks 24, 48, 96, and 240
Secondary	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
Secondary	Change from baseline in fibrosis as assessed by FibroTest at Weeks 24, 48, 96, and 240		Baseline; Weeks 24, 48, 96, and 240
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Percentage of participants with qHBsAg log10 IU/mL at Weeks 24, 48, 96, and 240		Weeks 24, 48, 96, and 240
Secondary	Incidence of resistance mutations at Weeks 24, 48, 96, and 240		Weeks 24, 48, 96, and 240
Secondary	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).	Baseline; Weeks 4, 24, and 36
Secondary	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).	Baseline; Weeks 4, 24, and 36
Secondary	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).	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)
Secondary	PK Parameter: AUClast of TAF and TFV	AUClast is defined as the concentration of drug from time zero to the last observable concentration.	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)
Secondary	PK Parameter: Ctau of TFV	Ctau is defined as the observed drug concentration at the end of the dosing interval.	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)
Secondary	PK Parameter: Cmax of TAF and TFV	Cmax is defined as the maximum observed concentration of drug.	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)
Secondary	PK Parameter: Clast of TAF and TFV	Clast is defined as the last observable concentration of drug.	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)
Secondary	PK Parameter: Tmax of TAF and TFV	Tmax is defined as the time of Cmax (the maximum concentration of drug).	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)
Secondary	PK Parameter: Tlast of TAF and TFV	Tlast is defined as the time (observed time point) of Clast.	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)
Secondary	PK Parameter: ?z of TAF and TFV	?z 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.	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)
Secondary	PK Parameter: CL/F of TAF and TFV	CL/F is defined as the apparent oral clearance following administration of the drug.	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)
Secondary	PK Parameter: Vz/F of TAF and TFV	Vz/F is defined as the apparent volume of distribution of the drug.	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)
Secondary	PK Parameter: t1/2 of TAF and TFV	t1/2 is defined as the estimate of the terminal elimination half-life of the drug.	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)

External Links

•   Gilead Clinical Trials Website