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

Primary Purpose

Chronic Hepatitis B

Status

Recruiting

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

TAF

Placebo

About this trial

This is an interventional treatment trial for Chronic Hepatitis B focused on measuring CHB, HBV

Eligibility Criteria

2 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Children's Hospital of Los AngelesRecruiting
Rady Childrens HospitalRecruiting
University of California, San Francisco (UCSF)Recruiting
Children's Hospital ColoradoRecruiting
University of Miami/Schiff Center for Liver Diseases
AdventHealth Medical Group
Children's Healthcare of Atlanta
Indiana University School of MedicineRecruiting
Johns Hopkins UniversityRecruiting
University of Minnesota Masonic Children's Hospital
Children's Mercy HospitalRecruiting
Children's Hospital & Medical Center
The Children's Hospital at MontefioreRecruiting
Cincinnati Children's Hospital Medical CenterRecruiting
Nationwide Children's HospitalRecruiting
Monroe Carell Jr. Children's Hospital at VanderbiltRecruiting
Children's Medical Center
Cook Children's Medical CenterRecruiting
Texas Children's Hospital - Main HospitalRecruiting
American Research Corporation at Texas Liver Institute
Seattle Children's HospitalRecruiting
West Virginia University Hospitals
Cliniques Universitaires Saint-LUC UCL
The Hospital for Sick Children
BC Children's Hospital
Prince of Wales HospitalRecruiting
SR Kalla Memorial Gastro And General Hospital
Pratha Gastro Liver Center
Institute of Post Graduation Medical Education & ResearchRecruiting
M. V Hospital and Research CenterRecruiting
Seth GS Medical College and KEM hospital, ParelRecruiting
Nandita Hospital and Research Centre
Khalatkar HospitalRecruiting
Midas Multispecility Hospital PVT. LTD.
All India Institute of Medical SciencesRecruiting
Surat Institute of Digestive SciencesRecruiting
Samvedna HospitalRecruiting
AOU di Bologna - Policlinico S. Orsola Malpighi - Dipartimento Malattic dell'Apparato Digerente e Medicina Intema
Kyungpook National University HospitalRecruiting
Seoul National University Hospital
Asan Medical CenterRecruiting
Samsung Medical CenterRecruiting
Severance Hospital, Yonsei University Health System
Auckland Clinical Studies LimitedRecruiting
Spitalul Grigore Alexandrescu-Sectia Pediatrie IIIRecruiting
Institutul National de Boli Infectioase "Prof.Dr. Matei Bals"Recruiting
Krasnoyarsk Regional Clinical Center of Maternal and Child Welfare
Federal Budgetary Institution of Science "Central Scientific-Research Institute of Epidemiology"
Federal Research Centre of Nutrition, Biotechnology and Food Safety
Scientific Center of Children's Health of the Ministry of Health of the Russian Federation
Federal State-Financed Institution Pediatric Research and Clinical Center for Infectious Diseases
Federal Budgetary Scientific Institution Pasteur St. Petersburg Scientific Research Institute of Epidemiology and Microbiology
Republican Clinical Hospital of Infectious Diseases named after A.F. Agafonov
Limited Medical Company Hepatolog
Kaohsiung Medical University Chung-Ho Memorial HospitalRecruiting
Chang Gung Medical Foundation, Kaohsiung Chang Gung Memorial Hospital
National Cheng Kung University HospitalRecruiting
National Taiwan University HospitalRecruiting
Taipei Mackay Memorial Hospital
Chang Gung Medical Foundation, Chang Gung Memorial Hospital, LinkouRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Arm Label

TAF (Cohort 1)

Placebo (Cohort 1)

TAF (Cohort 2 Group 1)

TAF (Cohort 2 Group 2)

TAF (Cohort 2 Group 3)

Cohort 2 Placebo

Open-Label TAF

Arm Description

Participants (12 to < 18 years) weighing ≥ 35 kg will receive TAF 25 mg tablet for 24 weeks

Participants (12 to < 18 years) weighing ≥ 35 kg will receive placebo tablet for 24 weeks

Participants (6 to < 12 years) weighing ≥ 25 kg will receive TAF 25 mg tablet for 24 weeks

Participants (6 to < 12 years) weighing ≥ 14 kg to < 25 kg will receive TAF 15 mg oral granules for 24 weeks

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)

Participants will receive matching placebo of TAF (tablet or oral granules) for 24 weeks.

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.

Outcomes

Primary Outcome Measures

Incidence of Treatment-Emergent Serious Adverse Events (SAEs) at Week 24

Incidence of Treatment-Emergent Adverse Events (AEs) at Week 24

Percentage of participants with plasma HBV DNA < 20 IU/mL at Week 24

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).

Secondary Outcome Measures

Percentage of participants experiencing graded laboratory abnormalities

Development as measured by Tanner Stage Assessment

Percentage change from baseline in bone mineral density (BMD) of whole body (minus head) by dual imaging x-ray absorptiometry (DXA)

Percentage change from baseline in BMD of lumbar spine by DXA

Change from baseline in serum creatinine

Change from baseline in estimated glomerular filtration rate (eGFR) by the Schwartz formula

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

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

Change from baseline in retinol-binding protein to creatine ratio at Weeks 4, 8, 12, 24, and 48

Change from baseline in beta-2-microglobulin to creatine ratio at Weeks 4, 8, 12, 24, and 48

Change from baseline in glucose at Weeks 4, 8, 12, 24, and 48

Change from baseline in phosphate at Weeks 4, 8, 12, 24, and 48

Percentage of participants with plasma HBV DNA < 20 IU/mL at 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

Percentage of participants with alanine aminotransferase (ALT) normalization at Weeks 24, 48, 96, and 240

Composite endpoint of percentage of participants with ALT normalization and HBV DNA < 20 IU/mL at Weeks 24, 48, 96 and 240

Change from baseline in fibrosis as assessed by FibroTest at 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

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)

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)

Percentage of participants with hepatitis B surface antigen (HBsAg) loss and seroconversion to anti-HBs at Weeks 24, 48, 96, and 240

Percentage of participants with qHBsAg log10 IU/mL at Weeks 24, 48, 96, and 240

Incidence of resistance mutations at Weeks 24, 48, 96, and 240

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).

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).

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).

PK Parameter: AUClast of TAF and TFV

AUClast is defined as the concentration of drug from time zero to the last observable concentration.

PK Parameter: Ctau of TFV

Ctau is defined as the observed drug concentration at the end of the dosing interval.

PK Parameter: Cmax of TAF and TFV

Cmax is defined as the maximum observed concentration of drug.

PK Parameter: Clast of TAF and TFV

Clast is defined as the last observable concentration of drug.

PK Parameter: Tmax of TAF and TFV

Tmax is defined as the time of Cmax (the maximum concentration of drug).

PK Parameter: Tlast of TAF and TFV

Tlast is defined as the time (observed time point) of Clast.

PK Parameter: λz of TAF and TFV

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

CL/F is defined as the apparent oral clearance following administration of the drug.

PK Parameter: Vz/F of TAF and TFV

Vz/F is defined as the apparent volume of distribution of the drug.

PK Parameter: t1/2 of TAF and TFV

t1/2 is defined as the estimate of the terminal elimination half-life of the drug.

Full Information

NCT ID

NCT02932150

First Posted

September 16, 2016

Last Updated

October 20, 2023

Sponsor

Gilead Sciences

1. Study Identification

Unique Protocol Identification Number

NCT02932150

Brief Title

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

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 2016 (Actual)

Primary Completion Date

August 2025 (Anticipated)

Study Completion Date

October 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Gilead Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Hepatitis B

Keywords

CHB, HBV

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

TAF (Cohort 1)

Arm Type

Experimental

Arm Description

Participants (12 to < 18 years) weighing ≥ 35 kg will receive TAF 25 mg tablet for 24 weeks

Arm Title

Placebo (Cohort 1)

Arm Type

Placebo Comparator

Arm Description

Participants (12 to < 18 years) weighing ≥ 35 kg will receive placebo tablet for 24 weeks

Arm Title

TAF (Cohort 2 Group 1)

Arm Type

Experimental

Arm Description

Participants (6 to < 12 years) weighing ≥ 25 kg will receive TAF 25 mg tablet for 24 weeks

Arm Title

TAF (Cohort 2 Group 2)

Arm Type

Experimental

Arm Description

Participants (6 to < 12 years) weighing ≥ 14 kg to < 25 kg will receive TAF 15 mg oral granules for 24 weeks

Arm Title

TAF (Cohort 2 Group 3)

Arm Type

Experimental

Arm Description

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)

Arm Title

Cohort 2 Placebo

Arm Type

Placebo Comparator

Arm Description

Participants will receive matching placebo of TAF (tablet or oral granules) for 24 weeks.

Arm Title

Open-Label TAF

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

TAF

Intervention Description

Administered orally once daily

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Administered orally once daily

Primary Outcome Measure Information:

Title

Incidence of Treatment-Emergent Serious Adverse Events (SAEs) at Week 24

Time Frame

Week 24

Title

Incidence of Treatment-Emergent Adverse Events (AEs) at Week 24

Time Frame

Week 24

Title

Percentage of participants with plasma HBV DNA < 20 IU/mL at Week 24

Time Frame

Week 24

Title

PK Parameter: AUCtau of TAF for participants from Cohort 2 Part A

Description

AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

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 Outcome Measure Information:

Title

Percentage of participants experiencing graded laboratory abnormalities

Time Frame

Weeks 24, 48, 96, and 240

Title

Development as measured by Tanner Stage Assessment

Time Frame

Weeks 24, 48, 96, and 240

Title

Percentage change from baseline in bone mineral density (BMD) of whole body (minus head) by dual imaging x-ray absorptiometry (DXA)

Time Frame

Baseline; Weeks 24, 48, 96, and 240

Title

Percentage change from baseline in BMD of lumbar spine by DXA

Time Frame

Baseline; Weeks 24, 48, 96, and 240

Title

Change from baseline in serum creatinine

Time Frame

Baseline; Weeks 4, 8, 12, 24, 48, 96, and 240

Title

Change from baseline in estimated glomerular filtration rate (eGFR) by the Schwartz formula

Time Frame

Baseline; Weeks 24, 48, 96, and 240

Title

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

Time Frame

Weeks 48, 96, and 240

Title

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

Time Frame

Weeks 48, 96, and 240

Title

Change from baseline in retinol-binding protein to creatine ratio at Weeks 4, 8, 12, 24, and 48

Time Frame

Baseline; Weeks 4, 8, 12, 24, and 48

Title

Change from baseline in beta-2-microglobulin to creatine ratio at Weeks 4, 8, 12, 24, and 48

Time Frame

Baseline; Weeks 4, 8, 12, 24, and 48

Title

Change from baseline in glucose at Weeks 4, 8, 12, 24, and 48

Time Frame

Baseline; Weeks 4, 8, 12, 24, and 48

Title

Change from baseline in phosphate at Weeks 4, 8, 12, 24, and 48

Time Frame

Baseline; Weeks 4, 8, 12, 24, and 48

Title

Percentage of participants with plasma HBV DNA < 20 IU/mL at Weeks 48, 96, and 240

Time Frame

Weeks 48, 96, and 240

Title

Proportion of participants with plasma HBV DNA < 20 IU/mL (target not detected) at Weeks 24, 48, 96, and 240

Time Frame

Weeks 24, 48, 96, and 240

Title

Percentage of participants with alanine aminotransferase (ALT) normalization at Weeks 24, 48, 96, and 240

Time Frame

Weeks 24, 48, 96, and 240

Title

Composite endpoint of percentage of participants with ALT normalization and HBV DNA < 20 IU/mL at Weeks 24, 48, 96 and 240

Time Frame

Weeks 24, 48, 96 and 240

Title

Change from baseline in fibrosis as assessed by FibroTest at Weeks 24, 48, 96, and 240

Time Frame

Baseline; Weeks 24, 48, 96, and 240

Title

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

Time Frame

Weeks 24, 48, 96, and 240

Title

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)

Time Frame

Weeks 24, 48, 96, and 240

Title

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)

Time Frame

Weeks 24, 48, 96, and 240

Title

Percentage of participants with hepatitis B surface antigen (HBsAg) loss and seroconversion to anti-HBs at Weeks 24, 48, 96, and 240

Time Frame

Weeks 24, 48, 96, and 240

Title

Percentage of participants with qHBsAg log10 IU/mL at Weeks 24, 48, 96, and 240

Time Frame

Weeks 24, 48, 96, and 240

Title

Incidence of resistance mutations at Weeks 24, 48, 96, and 240

Time Frame

Weeks 24, 48, 96, and 240

Title

Acceptability of study drug

Description

Time Frame

Baseline; Weeks 4, 24, and 36

Title

Palatability of study drug

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).

Time Frame

Baseline; Weeks 4, 24, and 36

Title

PK Parameter: AUCtau of tenofovir (TFV)

Description

AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

Time Frame