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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02932150




Registration number
NCT02932150
Ethics application status
Date submitted
16/09/2016
Date registered
13/10/2016
Date last updated
3/07/2024

Titles & IDs
Public title
Study of Tenofovir Alafenamide (TAF) in Children and Teen Participants With Chronic Hepatitis B Virus Infection
Scientific 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
Secondary ID [1] 0 0
2016-000785-37
Secondary ID [2] 0 0
GS-US-320-1092
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Hepatitis B 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - TAF
Treatment: Drugs - Placebo

Experimental: TAF (Cohort 1) - Participants (12 to \< 18 years) weighing = 35 kg will receive TAF 25 mg tablet for 24 weeks

Placebo comparator: Placebo (Cohort 1) - Participants (12 to \< 18 years) weighing = 35 kg will receive placebo tablet for 24 weeks

Experimental: TAF (Cohort 2 Group 1) - Participants (6 to \< 12 years) weighing = 25 kg will receive TAF 25 mg tablet for 24 weeks

Experimental: TAF (Cohort 2 Group 2) - Participants (6 to \< 12 years) weighing = 14 kg to \< 25 kg will receive TAF 15 mg oral granules for 24 weeks

Experimental: TAF (Cohort 2 Group 3) - 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)

Placebo comparator: Cohort 2 Placebo - Participants will receive matching placebo of TAF (tablet or oral granules) for 24 weeks.

Experimental: Open-Label 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.


Treatment: Drugs: TAF
Administered orally once daily

Treatment: Drugs: Placebo
Administered orally once daily

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Treatment-Emergent Serious Adverse Events (SAEs) at Week 24
Timepoint [1] 0 0
Week 24
Primary outcome [2] 0 0
Incidence of Treatment-Emergent Adverse Events (AEs) at Week 24
Timepoint [2] 0 0
Week 24
Primary outcome [3] 0 0
Percentage of participants with plasma HBV DNA < 20 IU/mL at Week 24
Timepoint [3] 0 0
Week 24
Primary outcome [4] 0 0
PK Parameter: AUCtau of TAF for participants from Cohort 2 Part A
Timepoint [4] 0 0
Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 or 12
Secondary outcome [1] 0 0
Percentage of participants experiencing graded laboratory abnormalities
Timepoint [1] 0 0
Weeks 24, 48, 96, and 240
Secondary outcome [2] 0 0
Development as measured by Tanner Stage Assessment
Timepoint [2] 0 0
Weeks 24, 48, 96, and 240
Secondary outcome [3] 0 0
Percentage change from baseline in bone mineral density (BMD) of whole body (minus head) by dual imaging x-ray absorptiometry (DXA)
Timepoint [3] 0 0
Baseline; Weeks 24, 48, 96, and 240
Secondary outcome [4] 0 0
Percentage change from baseline in BMD of lumbar spine by DXA
Timepoint [4] 0 0
Baseline; Weeks 24, 48, 96, and 240
Secondary outcome [5] 0 0
Change from baseline in serum creatinine
Timepoint [5] 0 0
Baseline; Weeks 4, 8, 12, 24, 48, 96, and 240
Secondary outcome [6] 0 0
Change from baseline in estimated glomerular filtration rate (eGFR) by the Schwartz formula
Timepoint [6] 0 0
Baseline; Weeks 24, 48, 96, and 240
Secondary outcome [7] 0 0
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
Timepoint [7] 0 0
Weeks 48, 96, and 240
Secondary outcome [8] 0 0
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
Timepoint [8] 0 0
Weeks 48, 96, and 240
Secondary outcome [9] 0 0
Change from baseline in retinol-binding protein to creatine ratio at Weeks 4, 8, 12, 24, and 48
Timepoint [9] 0 0
Baseline; Weeks 4, 8, 12, 24, and 48
Secondary outcome [10] 0 0
Change from baseline in beta-2-microglobulin to creatine ratio at Weeks 4, 8, 12, 24, and 48
Timepoint [10] 0 0
Baseline; Weeks 4, 8, 12, 24, and 48
Secondary outcome [11] 0 0
Change from baseline in glucose at Weeks 4, 8, 12, 24, and 48
Timepoint [11] 0 0
Baseline; Weeks 4, 8, 12, 24, and 48
Secondary outcome [12] 0 0
Change from baseline in phosphate at Weeks 4, 8, 12, 24, and 48
Timepoint [12] 0 0
Baseline; Weeks 4, 8, 12, 24, and 48
Secondary outcome [13] 0 0
Percentage of participants with plasma HBV DNA < 20 IU/mL at Weeks 48, 96, and 240
Timepoint [13] 0 0
Weeks 48, 96, and 240
Secondary outcome [14] 0 0
Proportion of participants with plasma HBV DNA < 20 IU/mL (target not detected) at Weeks 24, 48, 96, and 240
Timepoint [14] 0 0
Weeks 24, 48, 96, and 240
Secondary outcome [15] 0 0
Percentage of participants with alanine aminotransferase (ALT) normalization at Weeks 24, 48, 96, and 240
Timepoint [15] 0 0
Weeks 24, 48, 96, and 240
Secondary outcome [16] 0 0
Composite endpoint of percentage of participants with ALT normalization and HBV DNA < 20 IU/mL at Weeks 24, 48, 96 and 240
Timepoint [16] 0 0
Weeks 24, 48, 96 and 240
Secondary outcome [17] 0 0
Change from baseline in fibrosis as assessed by FibroTest at Weeks 24, 48, 96, and 240
Timepoint [17] 0 0
Baseline; Weeks 24, 48, 96, and 240
Secondary outcome [18] 0 0
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
Timepoint [18] 0 0
Weeks 24, 48, 96, and 240
Secondary outcome [19] 0 0
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)
Timepoint [19] 0 0
Weeks 24, 48, 96, and 240
Secondary outcome [20] 0 0
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)
Timepoint [20] 0 0
Weeks 24, 48, 96, and 240
Secondary outcome [21] 0 0
Percentage of participants with hepatitis B surface antigen (HBsAg) loss and seroconversion to anti-HBs at Weeks 24, 48, 96, and 240
Timepoint [21] 0 0
Weeks 24, 48, 96, and 240
Secondary outcome [22] 0 0
Percentage of participants with qHBsAg log10 IU/mL at Weeks 24, 48, 96, and 240
Timepoint [22] 0 0
Weeks 24, 48, 96, and 240
Secondary outcome [23] 0 0
Incidence of resistance mutations at Weeks 24, 48, 96, and 240
Timepoint [23] 0 0
Weeks 24, 48, 96, and 240
Secondary outcome [24] 0 0
Acceptability of study drug
Timepoint [24] 0 0
Baseline; Weeks 4, 24, and 36
Secondary outcome [25] 0 0
Palatability of study drug
Timepoint [25] 0 0
Baseline; Weeks 4, 24, and 36
Secondary outcome [26] 0 0
PK Parameter: AUCtau of tenofovir (TFV)
Timepoint [26] 0 0
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 outcome [27] 0 0
PK Parameter: AUClast of TAF and TFV
Timepoint [27] 0 0
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 outcome [28] 0 0
PK Parameter: Ctau of TFV
Timepoint [28] 0 0
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 outcome [29] 0 0
PK Parameter: Cmax of TAF and TFV
Timepoint [29] 0 0
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 outcome [30] 0 0
PK Parameter: Clast of TAF and TFV
Timepoint [30] 0 0
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 outcome [31] 0 0
PK Parameter: Tmax of TAF and TFV
Timepoint [31] 0 0
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 outcome [32] 0 0
PK Parameter: Tlast of TAF and TFV
Timepoint [32] 0 0
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 outcome [33] 0 0
PK Parameter: ?z of TAF and TFV
Timepoint [33] 0 0
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 outcome [34] 0 0
PK Parameter: CL/F of TAF and TFV
Timepoint [34] 0 0
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 outcome [35] 0 0
PK Parameter: Vz/F of TAF and TFV
Timepoint [35] 0 0
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 outcome [36] 0 0
PK Parameter: t1/2 of TAF and TFV
Timepoint [36] 0 0
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)

Eligibility
Key inclusion 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
Minimum age
2 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
Nebraska
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Tennessee
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Washington
Country [15] 0 0
United States of America
State/province [15] 0 0
West Virginia
Country [16] 0 0
Belgium
State/province [16] 0 0
Brussels
Country [17] 0 0
Canada
State/province [17] 0 0
Toronto
Country [18] 0 0
Canada
State/province [18] 0 0
Vancouver
Country [19] 0 0
Hong Kong
State/province [19] 0 0
Shatin
Country [20] 0 0
India
State/province [20] 0 0
Ahmedabad
Country [21] 0 0
India
State/province [21] 0 0
Jaipur
Country [22] 0 0
India
State/province [22] 0 0
Kanpur
Country [23] 0 0
India
State/province [23] 0 0
Kolkata
Country [24] 0 0
India
State/province [24] 0 0
Lucknow
Country [25] 0 0
India
State/province [25] 0 0
Mumbai
Country [26] 0 0
India
State/province [26] 0 0
Nagpur
Country [27] 0 0
India
State/province [27] 0 0
New Delhi
Country [28] 0 0
India
State/province [28] 0 0
Surat
Country [29] 0 0
India
State/province [29] 0 0
Varanasi
Country [30] 0 0
Italy
State/province [30] 0 0
Bologna
Country [31] 0 0
Korea, Republic of
State/province [31] 0 0
Daegu
Country [32] 0 0
Korea, Republic of
State/province [32] 0 0
Seoul
Country [33] 0 0
New Zealand
State/province [33] 0 0
Auckland
Country [34] 0 0
Romania
State/province [34] 0 0
Bucharest
Country [35] 0 0
Russian Federation
State/province [35] 0 0
Krasnoyarsk
Country [36] 0 0
Russian Federation
State/province [36] 0 0
Moscow
Country [37] 0 0
Russian Federation
State/province [37] 0 0
Saint-Petersburg
Country [38] 0 0
Russian Federation
State/province [38] 0 0
Tatarstan
Country [39] 0 0
Russian Federation
State/province [39] 0 0
Tolyatti
Country [40] 0 0
Taiwan
State/province [40] 0 0
Kaohsiung City
Country [41] 0 0
Taiwan
State/province [41] 0 0
Kaohsiung
Country [42] 0 0
Taiwan
State/province [42] 0 0
Tainan
Country [43] 0 0
Taiwan
State/province [43] 0 0
Taipei
Country [44] 0 0
Taiwan
State/province [44] 0 0
Taoyuan

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gilead Study Director
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Gilead Study Team
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.