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.
Brief Title
Study of Tenofovir Alafenamide (TAF) in Children and Teen Participants With Chronic Hepatitis B Virus Infection
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Email
GS-US-320-1092@gilead.com
Completion Date
Completion Date Type
Estimated
Conditions
Chronic Hepatitis B
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.
* 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.
Inclusion Criteria
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
Inclusion/
* 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
Inclusion/
Gender
All
Gender Based
false
Keywords
CHB
HBV
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
17 Years
Minimum Age
2 Years
NCT Id
NCT02932150
Org Class
Industry
Org Full Name
Gilead Sciences
Org Study Id
GS-US-320-1092
Overall Status
Recruiting
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Estimated
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
Primary Outcomes
Outcome Measure
Incidence of Treatment-Emergent Serious Adverse Events (SAEs) at Week 24
Outcome Time Frame
Week 24
Outcome Measure
Incidence of Treatment-Emergent Adverse Events (AEs) at Week 24
Outcome Time Frame
Week 24
Outcome Measure
Percentage of participants with plasma HBV DNA < 20 IU/mL at Week 24
Outcome Time Frame
Week 24
Outcome Description
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Outcome Measure
PK Parameter: AUCtau of TAF for participants from Cohort 2 Part A
Outcome Time Frame
Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 or 12
Secondary Ids
Secondary Id
2016-000785-37
Secondary Id
2023-506143-42
Secondary Outcomes
Outcome Time Frame
Weeks 24, 48, 96, and 240
Outcome Measure
Percentage of participants experiencing graded laboratory abnormalities
Outcome Time Frame
Weeks 24, 48, 96, and 240
Outcome Measure
Development as measured by Tanner Stage Assessment
Outcome Time Frame
Baseline; Weeks 24, 48, 96, and 240
Outcome Measure
Percentage change from baseline in bone mineral density (BMD) of whole body (minus head) by dual imaging x-ray absorptiometry (DXA)
Outcome Time Frame
Baseline; Weeks 24, 48, 96, and 240
Outcome Measure
Percentage change from baseline in BMD of lumbar spine by DXA
Outcome Time Frame
Baseline; Weeks 4, 8, 12, 24, 48, 96, and 240
Outcome Measure
Change from baseline in serum creatinine
Outcome Time Frame
Baseline; Weeks 24, 48, 96, and 240
Outcome Measure
Change from baseline in estimated glomerular filtration rate (eGFR) by the Schwartz formula
Outcome Time Frame
Weeks 48, 96, and 240
Outcome 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
Outcome Time Frame
Weeks 48, 96, and 240
Outcome 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
Outcome Time Frame
Baseline; Weeks 4, 8, 12, 24, and 48
Outcome Measure
Change from baseline in retinol-binding protein to creatine ratio at Weeks 4, 8, 12, 24, and 48
Outcome Time Frame
Baseline; Weeks 4, 8, 12, 24, and 48
Outcome Measure
Change from baseline in beta-2-microglobulin to creatine ratio at Weeks 4, 8, 12, 24, and 48
Outcome Time Frame
Baseline; Weeks 4, 8, 12, 24, and 48
Outcome Measure
Change from baseline in glucose at Weeks 4, 8, 12, 24, and 48
Outcome Time Frame
Baseline; Weeks 4, 8, 12, 24, and 48
Outcome Measure
Change from baseline in phosphate at Weeks 4, 8, 12, 24, and 48
Outcome Time Frame
Weeks 48, 96, and 240
Outcome Measure
Percentage of participants with plasma HBV DNA < 20 IU/mL at Weeks 48, 96, and 240
Outcome Time Frame
Weeks 24, 48, 96, and 240
Outcome Measure
Proportion of participants with plasma HBV DNA < 20 IU/mL (target not detected) at Weeks 24, 48, 96, and 240
Outcome Time Frame
Weeks 24, 48, 96, and 240
Outcome Measure
Percentage of participants with alanine aminotransferase (ALT) normalization at Weeks 24, 48, 96, and 240
Outcome Time Frame
Weeks 24, 48, 96 and 240
Outcome Measure
Composite endpoint of percentage of participants with ALT normalization and HBV DNA < 20 IU/mL at Weeks 24, 48, 96 and 240
Outcome Time Frame
Baseline; Weeks 24, 48, 96, and 240
Outcome Measure
Change from baseline in fibrosis as assessed by FibroTest at Weeks 24, 48, 96, and 240
Outcome Time Frame
Weeks 24, 48, 96, and 240
Outcome 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
Outcome Time Frame
Weeks 24, 48, 96, and 240
Outcome 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)
Outcome Time Frame
Weeks 24, 48, 96, and 240
Outcome 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)
Outcome Time Frame
Weeks 24, 48, 96, and 240
Outcome Measure
Percentage of participants with hepatitis B surface antigen (HBsAg) loss and seroconversion to anti-HBs at Weeks 24, 48, 96, and 240
Outcome Time Frame
Weeks 24, 48, 96, and 240
Outcome Measure
Percentage of participants with qHBsAg log10 IU/mL at Weeks 24, 48, 96, and 240
Outcome Time Frame
Weeks 24, 48, 96, and 240
Outcome Measure
Incidence of resistance mutations at Weeks 24, 48, 96, and 240
Outcome Description
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).
Outcome Time Frame
Baseline; Weeks 4, 24, and 36
Outcome Measure
Acceptability of study drug
Outcome Description
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).
Outcome Time Frame
Baseline; Weeks 4, 24, and 36
Outcome Measure
Palatability of study drug
Outcome Description
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Outcome Time Frame
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)
Outcome Measure
PK Parameter: AUCtau of tenofovir (TFV)
Outcome Description
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Outcome Time Frame
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)
Outcome Measure
PK Parameter: AUClast of TAF and TFV
Outcome Description
Ctau is defined as the observed drug concentration at the end of the dosing interval.
Outcome Time Frame
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)
Outcome Measure
PK Parameter: Ctau of TFV
Outcome Description
Cmax is defined as the maximum observed concentration of drug.
Outcome Time Frame
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)
Outcome Measure
PK Parameter: Cmax of TAF and TFV
Outcome Description
Clast is defined as the last observable concentration of drug.
Outcome Time Frame
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)
Outcome Measure
PK Parameter: Clast of TAF and TFV
Outcome Description
Tmax is defined as the time of Cmax (the maximum concentration of drug).
Outcome Time Frame
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)
Outcome Measure
PK Parameter: Tmax of TAF and TFV
Outcome Description
Tlast is defined as the time (observed time point) of Clast.
Outcome Time Frame
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)
Outcome Measure
PK Parameter: Tlast of TAF and TFV
Outcome Description
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.
Outcome Time Frame
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)
Outcome Measure
PK Parameter: λz of TAF and TFV
Outcome Description
CL/F is defined as the apparent oral clearance following administration of the drug.
Outcome Time Frame
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)
Outcome Measure
PK Parameter: CL/F of TAF and TFV
Outcome Description
Vz/F is defined as the apparent volume of distribution of the drug.
Outcome Time Frame
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)
Outcome Measure
PK Parameter: Vz/F of TAF and TFV
Outcome Description
t1/2 is defined as the estimate of the terminal elimination half-life of the drug.
Outcome Time Frame
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)
Outcome Measure
PK Parameter: t1/2 of TAF and TFV
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Child
Locked Fields
Render the field
Maximum Age Number (converted to Years and rounded down)
17
Minimum Age Number (converted to Years and rounded down)
2
Investigators
Investigator Type
Principal Investigator
Investigator Name
Debra Pan
Investigator Email
dpan@montefiore.org
Investigator Phone
718-741-2332