Clinical trial NCT02932150: Study of Tenofovir Alafenamide (TAF) in Children and Teen Participants With Chronic Hepatitis B Virus Infection
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Chronic Hepatitis B
Keywords: CHB
HBV
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2016-10-13
Enrollment: 150
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Incidence of Treatment-Emergent Serious Adverse Events (SAEs) at Week 24
timeFrame: Week 24
measure: Incidence of Treatment-Emergent Adverse Events (AEs) at Week 24
timeFrame: Week 24
measure: Percentage of participants with plasma HBV DNA < 20 IU/mL at Week 24
timeFrame: Week 24
measure: PK Parameter: AUCtau of TAF for participants from Cohort 2 Part A
timeFrame: 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:
measure: Percentage of participants experiencing graded laboratory abnormalities
timeFrame: Weeks 24, 48, 96, and 240
measure: Development as measured by Tanner Stage Assessment
timeFrame: Weeks 24, 48, 96, and 240
measure: Percentage change from baseline in bone mineral density (BMD) of whole body (minus head) by dual imaging x-ray absorptiometry (DXA)
timeFrame: Baseline; Weeks 24, 48, 96, and 240
measure: Percentage change from baseline in BMD of lumbar spine by DXA
timeFrame: Baseline; Weeks 24, 48, 96, and 240
measure: Change from baseline in serum creatinine
timeFrame: Baseline; Weeks 4, 8, 12, 24, 48, 96, and 240
measure: Change from baseline in estimated glomerular filtration rate (eGFR) by the Schwartz formula
timeFrame: Baseline; Weeks 24, 48, 96, and 240
measure: 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
timeFrame: Weeks 48, 96, and 240
measure: 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
timeFrame: Weeks 48, 96, and 240
measure: Change from baseline in retinol-binding protein to creatine ratio at Weeks 4, 8, 12, 24, and 48
timeFrame: Baseline; Weeks 4, 8, 12, 24, and 48
measure: Change from baseline in beta-2-microglobulin to creatine ratio at Weeks 4, 8, 12, 24, and 48
timeFrame: Baseline; Weeks 4, 8, 12, 24, and 48
measure: Change from baseline in glucose at Weeks 4, 8, 12, 24, and 48
timeFrame: Baseline; Weeks 4, 8, 12, 24, and 48
measure: Change from baseline in phosphate at Weeks 4, 8, 12, 24, and 48
timeFrame: Baseline; Weeks 4, 8, 12, 24, and 48
measure: Percentage of participants with plasma HBV DNA < 20 IU/mL at Weeks 48, 96, and 240
timeFrame: Weeks 48, 96, and 240
measure: Proportion of participants with plasma HBV DNA < 20 IU/mL (target not detected) at Weeks 24, 48, 96, and 240
timeFrame: Weeks 24, 48, 96, and 240
measure: Percentage of participants with alanine aminotransferase (ALT) normalization at Weeks 24, 48, 96, and 240
timeFrame: Weeks 24, 48, 96, and 240
measure: Composite endpoint of percentage of participants with ALT normalization and HBV DNA < 20 IU/mL at Weeks 24, 48, 96 and 240
timeFrame: Weeks 24, 48, 96 and 240
measure: Change from baseline in fibrosis as assessed by FibroTest at Weeks 24, 48, 96, and 240
timeFrame: Baseline; Weeks 24, 48, 96, and 240
measure: 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
timeFrame: Weeks 24, 48, 96, and 240
measure: 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)
timeFrame: Weeks 24, 48, 96, and 240
measure: 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)
timeFrame: Weeks 24, 48, 96, and 240
measure: Percentage of participants with hepatitis B surface antigen (HBsAg) loss and seroconversion to anti-HBs at Weeks 24, 48, 96, and 240
timeFrame: Weeks 24, 48, 96, and 240
measure: Percentage of participants with qHBsAg log10 IU/mL at Weeks 24, 48, 96, and 240
timeFrame: Weeks 24, 48, 96, and 240
measure: Incidence of resistance mutations at Weeks 24, 48, 96, and 240
timeFrame: Weeks 24, 48, 96, and 240
measure: Acceptability of study drug
timeFrame: Baseline; Weeks 4, 24, and 36
measure: Palatability of study drug
timeFrame: Baseline; Weeks 4, 24, and 36
measure: PK Parameter: AUCtau of tenofovir (TFV)
timeFrame: 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)
measure: PK Parameter: AUClast of TAF and TFV
timeFrame: 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)
measure: PK Parameter: Ctau of TFV
timeFrame: 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)
measure: PK Parameter: Cmax of TAF and TFV
timeFrame: 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)
measure: PK Parameter: Clast of TAF and TFV
timeFrame: 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)
measure: PK Parameter: Tmax of TAF and TFV
timeFrame: 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)
measure: PK Parameter: Tlast of TAF and TFV
timeFrame: 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)
measure: PK Parameter: λz of TAF and TFV
timeFrame: 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)
measure: PK Parameter: CL/F of TAF and TFV
timeFrame: 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)
measure: PK Parameter: Vz/F of TAF and TFV
timeFrame: 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)
measure: PK Parameter: t1/2 of TAF and TFV
timeFrame: 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)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: San Diego
country: United States
facility: Rady Childrens Hospital
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco (UCSF)
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Miami
country: United States
facility: University of Miami/Schiff Center for Liver Diseases
state: Florida
city: Orlando
country: United States
facility: AdventHealth Medical Group
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Minneapolis
country: United States
facility: University of Minnesota Masonic Children's Hospital
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Omaha
country: United States
facility: Children's Hospital & Medical Center
state: Nebraska
city: Bronx
country: United States
facility: The Children's Hospital at Montefiore
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Nashville
country: United States
facility: Monroe Carell Jr. Children's Hospital at Vanderbilt
state: Tennessee
city: Dallas
country: United States
facility: Children's Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital - Main Hospital
state: Texas
city: San Antonio
country: United States
facility: American Research Corporation at Texas Liver Institute
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Morgantown
country: United States
facility: West Virginia University Hospitals
state: West Virginia
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-LUC UCL
city: Toronto
country: Canada
facility: The Hospital for Sick Children
city: Vancouver
country: Canada
facility: BC Children's Hospital
city: Shatin
country: Hong Kong
facility: Prince of Wales Hospital
city: Ahmedabad
country: India
facility: GCS Medical Hospital & Research Center
city: Jaipur
country: India
facility: SR Kalla Memorial Gastro And General Hospital
city: Kanpur
country: India
facility: Pratha Gastro Liver Center
city: Kolkata
country: India
facility: Institute of Post Graduation Medical Education & Research
city: Lucknow
country: India
facility: M. V Hospital and Research Center
city: Mumbai
country: India
facility: Seth GS Medical College and KEM Hospital
city: Mumbai
country: India
facility: LTMMC & LTMG Hospital
city: Nagpur
country: India
facility: Nandita Hospital and Research Centre
city: Nagpur
country: India
facility: Khalatkar Hospital
city: Nagpur
country: India
facility: Midas Multispecility Hospital PVT. LTD.
city: New Delhi
country: India
facility: All India Institute of Medical Sciences
city: Surat
country: India
facility: SIDS Hospital and Research Centre
city: Varanasi
country: India
facility: Samvedna Hospital
city: Bologna
country: Italy
facility: AOU di Bologna - Policlinico S. Orsola Malpighi - Dipartimento Malattic dell'Apparato Digerente e Medicina Intema
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Auckland
country: New Zealand
facility: Auckland Clinical Studies Limited
city: Bucharest
country: Romania
facility: Spitalul Grigore Alexandrescu-Sectia Pediatrie III
city: Bucharest
country: Romania
facility: Institutul National de Boli Infectioase "Prof.Dr. Matei Bals"
city: Krasnoyarsk
country: Russian Federation
facility: Krasnoyarsk Regional Clinical Center of Maternal and Child Welfare
city: Moscow
country: Russian Federation
facility: Federal Budgetary Institution of Science "Central Scientific-Research Institute of Epidemiology"
city: Moscow
country: Russian Federation
facility: Federal Research Centre of Nutrition, Biotechnology and Food Safety
city: Moscow
country: Russian Federation
facility: Scientific Center of Children's Health of the Ministry of Health of the Russian Federation
city: Saint-Petersburg
country: Russian Federation
facility: Federal State-Financed Institution Pediatric Research and Clinical Center for Infectious Diseases
city: Saint-Petersburg
country: Russian Federation
facility: Federal Budgetary Scientific Institution Pasteur St. Petersburg Scientific Research Institute of Epidemiology and Microbiology
city: Tatarstan
country: Russian Federation
facility: Republican Clinical Hospital of Infectious Diseases named after A.F. Agafonov
city: Tolyatti
country: Russian Federation
facility: Limited Medical Company Hepatolog
city: Kaohsiung City
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: Chang Gung Medical Foundation, Kaohsiung Chang Gung Memorial Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Mackay Memorial Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation, Chang Gung Memorial Hospital, Linkou
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: