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Evaluation of Tenofovir Disoproxil Fumarate in Adolescents With Chronic Hepatitis B Infection

Primary Purpose

Hepatitis B Virus (HBV)

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Tenofovir disoproxil fumarate (TDF)

Placebo

About this trial

This is an interventional treatment trial for Hepatitis B Virus (HBV) focused on measuring tenofovir, adolescents, chronic hepatitis B

Eligibility Criteria

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

Inclusion Criteria

Male or female, 12 through 17 years of age, inclusive (consent of parent/legal guardian required)
Documented chronic HBV infection
HBeAg positive or HBeAg negative
Weight > 35 kg
Able to swallow oral tablets
HBV DNA > 100,000 copies/mL (polymerase chain reaction (PCR) method)
Alanine aminotransferase (ALT) > 2 × upper limit of normal (ULN) at screening, OR any history of ALT > 2 × ULN over the past 24 months
Willing and able to provide written informed consent/assent (child and parent/legal guardian)
Negative serum pregnancy test (for postmenarchal females only)
Estimated glomerular filtration rate (creatinine clearance [using the Schwartz formula]) > 80 mL/min/1.73m^2
Adequate hematologic function (absolute neutrophil count ≥ 1,500/mm^3; hemoglobin ≥ 10.0 g/dL)
No prior TDF therapy (participants may have received prior interferon or oral anti-HBV nucleoside/nucleotide therapy; participants must have discontinued interferon therapy ≥ 6 months prior to screening; participants experienced on anti-HBV nucleoside/nucleotide therapy must have discontinued therapy ≥ 16 weeks prior to screening to avoid flare if randomized to the placebo arm)

Exclusion Criteria

Pregnant women, women who are breast feeding or who believe they may wish to become pregnant during the course of the study
Males and females of reproductive potential who are not willing to use an effective method of contraception during the study
Decompensated liver disease
Receipt of interferon (pegylated or not) therapy within 6 months of the Screening Visit
Receipt of anti-HBV nucleoside/nucleotide therapy within 16 weeks of the Screening Visit
Alpha fetoprotein > 50 ng/mL
Evidence of hepatocellular carcinoma (HCC)
Coinfection with HIV, hepatitis C virus (HCV), or hepatitis D virus (HDV)
History of significant renal disease (eg, nephrotic syndrome, renal dysgenesis, polycystic kidney disease, congenital nephrosis, acute tubular necrosis, other renal disease)
History of significant bone disease (eg, osteomalacia, chronic osteomyelitis, osteogenesis imperfecta, osteochondroses, multiple bone fractures)
Significant cardiovascular, pulmonary, or neurological disease
Evidence of a gastrointestinal malabsorption syndrome that may interfere with absorption of orally administered medications
History of solid organ or bone marrow transplantation
Ongoing therapy with nephrotoxic agents, competitors of renal excretion, systemic chemotherapeutic agents, systemic corticosteroids, interleukin-2 (IL-2), or other immunomodulating or investigational agents
Known hypersensitivity to the study drugs, the metabolites or formulation excipients
Any other condition (including alcohol or substance abuse) or prior therapy that, in the opinion of the Investigator, would make the participants unsuitable for the study or unable to comply with dosing requirements

Sites / Locations

Children's Hospital & Research Center at Oakland
Riley Hospital for Children
Children's Hospital & Regional Medical Center, d/b/a Seattle Children's Research Institute
Multiprofile Hospital for Active Treatment Sveti Georgi
Clinic of Gastroenterology, Specialized Hospital for Active Treatment of Pediatric Diseases, Sofia
Hopital Femmes Meres Enfants
Hôpital Claude Huriez
Samodzielny Publiczny Dzieciecy Szpital Kliniczny Akademii Medycznej w Bialymstoku
Wojewodzki Specjalistyczny Szpital im Bieganskiego
Wojewodzki Szpital Obserwacyjno-Zakazny im. T. Browicza
Krakowski Szpital Specjalistyczny im. Jana Pawla II
Samodzielny Publiczny Szpital Kliniczny im. Karola Johschera
Specjalistyczny Zespol Opieki Zdrowotnej nad Matka i Dzieckiem
Wojewodzki Szpital Zakazny
Samodzielny Publiczny Szpital Kliniczny Nr 1
Fundeni Clinical Institute
Institute for Infectious Diseases
Cluj Childrens Emergency Hospital
Hosp Univ y Politecnico La Fe de Valencia
Hospital Universitario De Getafe
Ege Universitesi Tip Fakultesi Hastanesi

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Tenofovir disoproxil fumarate (TDF)

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Percentage of Participants With HBV DNA < 400 Copies/mL at Week 72

The percentage of participants with HBV DNA < 400 copies/mL at Week 72 was summarized by treatment and age group (grouped by baseline age for analysis), using the missing = failure (M = F) analysis with the double-blind efficacy evaluation (DBEE) algorithm. In the M = F analysis method, all missing data were considered as failure to meet the outcome measure threshold. This method was combined with the DBEE algorithm, which included all available data for the double-blind period, and any data for the open-label period were not included; data generated during treatment-free follow-up from subjects who achieved HBsAg loss and entered treatment-free follow-up during double-blind treatment period were included.

Percentage of Participants With at Least a 6% Decrease From Baseline in Bone Mineral Density (BMD) of the Spine at Week 72

Data were summarized by treatment and age group (grouped by baseline age for analysis). In contrast with what was previously reported in the interim results posting, 1 participant met the primary safety endpoint of at least a 6% decrease from baseline in spine BMD at Week 72, based on the final BMD data analysis. The apparent discrepancy was due to the correction factor applied to the subject-specific BMD calculations performed at the time of the Interim Week 72 clinical study report that could not take into account the actual Week 72 phantom data (ie, calibration test used in longitudinal clinical trials to monitor and adjust for shifts in the dual-energy x-ray absorptiometry (DXA) scanner calibration over time), which were not provided by the site at that time. The correction factor applied to the final analysis has been properly based on all phantom data through the end of Week 72, as well as through the end of Week 192.

Secondary Outcome Measures

Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 96, 144, and 192

Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.

Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Weeks 48, 72, 96, 144, and 192

Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.

Percentage of Participants With HBV DNA < 400 Copies/mL and Normal ALT at Weeks 48, 72, 96, 144, and 192

Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.

Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 72, 96, 144, and 192

Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.

Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48, 72, 96, 144, and 192

Data were summarized by treatment and age group (grouped by baseline age for analysis), using the M = F.

Percentage of Participants With HBsAg Seroconversion at Weeks 48, 72, 96, 144, and 192

HBsAg seroconversion was defined as change of detectable antibody to HBsAg from negative to positive. Data were summarized by treatment and age group (grouped by baseline age for analysis), using the M = F.

Percentage of Participants With at Least a 6% Decrease From Baseline in Spine BMD at Weeks 48, 96, 144, and 192

The percentage of participants reported is the cumulative incidence from baseline to the respective time point. Data were summarized by treatment and age group (grouped by baseline age for analysis).

Percentage of Participants With at Least a 6% Decrease From Baseline in Whole Body BMD at Weeks 48, 72, 96, 144, and 192

The percentage of participants reported is the cumulative incidence from baseline to the respective time point. Data were summarized by treatment and age group (grouped by baseline age for analysis).

Percent Change From Baseline in Spine Bone Mineral Density (BMD) at Week 48

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Percent Change From Baseline in Spine BMD at Week 72

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Percent Change From Baseline in Spine BMD at Week 96

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Percent Change From Baseline in Spine BMD at Week 144

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Percent Change From Baseline in Spine BMD at Week 192

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Percent Change From Baseline in Whole Body BMD at Week 48

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Percent Change From Baseline in Whole Body BMD at Week 72

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Percent Change From Baseline in Whole Body BMD at Week 96

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Percent Change From Baseline in Whole Body BMD at Week 144

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Percent Change From Baseline in Whole Body BMD at Week 192

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Change From Baseline in Z-score for Spine BMD at Week 48

To assess any effect of treatment on growth, Z-scores were used to express the deviation from a reference population for lumbar spine BMD. A Z-score of 0 indicated that a subject was typical of the population for their age, ethnicity, and gender. A negative Z-score indicated that the subject's recorded value was lower than typical for their age, ethnicity, and gender. A positive Z-score indicates that the subject's recorded value was higher than typical for their age, ethnicity, and gender. Data were summarized by treatment and age group (grouped by baseline age for analysis).

Change From Baseline in Z-score for Spine BMD at Week 72

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Change From Baseline in Z-score for Spine BMD at Week 96

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Change From Baseline in Z-score for Spine BMD at Week 144

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Change From Baseline in Z-score for Spine BMD at Week 192

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Change From Baseline in Z-score for Whole Body BMD at Week 48

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Change From Baseline in Z-score for Whole Body BMD at Week 72

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Change From Baseline in Z-score for Whole Body BMD at Week 96

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Change From Baseline in Z-score for Whole Body BMD at Week 144

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Change From Baseline in Z-score for Whole Body BMD at Week 192

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Number of Participants With Changes in Drug-Resistant Mutations During the Study

The number of participants with changes in drug-resistant mutations during the study was summarized.

Percentage of Participants Who Were HBeAg-Positive at Baseline and Who Had HBeAg Loss at Weeks 48, 72, 96, 144, and 192

Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.

Percentage of Participants Who Were HBeAg-Positive at Baseline and Who Had HBeAg Seroconversion at Weeks 48, 72, 96, 144, and 192

Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.

Percentage of Participants Who Were HBeAg-Positive at Baseline Who Had HBV DNA < 400 Copies/mL, Normal ALT, and HBeAg Loss/Seroconversion at Weeks 48, 72, 96, 144, and 192

Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.

Percentage of Participants With Abnormal ALT at Baseline Who Had Normalized ALT at Weeks 48, 72, 96, 144, and 192

Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.

Percentage of Participants With Abnormal ALT at Baseline Who Had HBV DNA < 400 Copies/mL and Normalized ALT at Weeks 48, 72, 96, 144, and 192

Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.

Percentage of Participants Who Were HBeAg-Positive With Abnormal ALT at Baseline Who Had HBV DNA < 400 Copies/mL, Normalized ALT, and HBeAg Loss/Seroconversion at Weeks 48, 72, 96, 144, and 192

Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.

Full Information

NCT ID

NCT00734162

First Posted

August 13, 2008

Last Updated

July 20, 2016

Sponsor

Gilead Sciences

1. Study Identification

Unique Protocol Identification Number

NCT00734162

Brief Title

Evaluation of Tenofovir Disoproxil Fumarate in Adolescents With Chronic Hepatitis B Infection

Official Title

A Randomized, Double-Blind Evaluation of the Antiviral Efficacy, Safety, and Tolerability of Tenofovir Disoproxil Fumarate Versus Placebo in Adolescents With Chronic Hepatitis B Infection

Study Type

Interventional

2. Study Status

Record Verification Date

July 2016

Overall Recruitment Status

Completed

Study Start Date

December 2008 (undefined)

Primary Completion Date

March 2011 (Actual)

Study Completion Date

December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Gilead Sciences

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The primary purpose of the study is to evaluate the effectiveness, safety, and tolerability of tenofovir disoproxil fumarate (TDF) in adolescents (aged 12-17 years) with chronic hepatitis B virus (HBV) infection. The optimal treatment for adolescents with chronic HBV infection is currently unknown. Treatment with interferon alfa, lamivudine, and adefovir dipivoxil in pediatric populations has been shown to be less than optimal. Further, the safety and efficacy of entecavir and telbivudine have not been established in patients < 16 years of age. A study evaluating TDF in adolescents (ages 12-17) was needed to assess the safety and efficacy of this agent in the treatment of chronic hepatitis B in this patient population. In addition, the study will help to further elucidate the pharmacokinetic (PK) and resistance profiles of TDF. Through their participation, study participants will help generate critical new information to help guide the most optimal treatment of chronic HBV infection in adolescents. This is a randomized, double-blind study to evaluate the antiviral efficacy, safety, and tolerability of TDF versus placebo in adolescents with chronic HBV infection. TDF treatment-naive participants were randomized in a 1:1 ratio to TDF or placebo. After 72 weeks of blinded treatment, participants were to switch to open-label TDF for an additional 2.5 years of treatment, provided that no safety concerns are identified by the Independent Data Monitoring Committee monitoring the study.

6. Conditions and Keywords

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

Hepatitis B Virus (HBV)

Keywords

tenofovir, adolescents, chronic hepatitis B

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

106 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Tenofovir disoproxil fumarate (TDF)

Arm Type

Experimental

Arm Title

Placebo

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

Tenofovir disoproxil fumarate (TDF)

Other Intervention Name(s)

Viread®

Intervention Description

TDF administered as a 300-mg tablet once daily

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

TDF placebo tablet once daily

Primary Outcome Measure Information:

Title

Percentage of Participants With HBV DNA < 400 Copies/mL at Week 72

Description

Time Frame

Week 72

Title

Percentage of Participants With at Least a 6% Decrease From Baseline in Bone Mineral Density (BMD) of the Spine at Week 72

Description

Time Frame

Baseline to Week 72

Secondary Outcome Measure Information:

Title

Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 96, 144, and 192

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.

Time Frame

Weeks 48, 96, 144, and 192

Title

Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Weeks 48, 72, 96, 144, and 192

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.

Time Frame

Weeks 48, 72, 96, 144, and 192

Title

Percentage of Participants With HBV DNA < 400 Copies/mL and Normal ALT at Weeks 48, 72, 96, 144, and 192

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.

Time Frame

Weeks 48, 72, 96, 144, and 192

Title

Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 72, 96, 144, and 192

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.

Time Frame

Weeks 48, 72, 96, 144, and 192

Title

Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48, 72, 96, 144, and 192

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis), using the M = F.

Time Frame

Baseline; Weeks 48, 72, 96, 144, and 192

Title

Percentage of Participants With HBsAg Seroconversion at Weeks 48, 72, 96, 144, and 192

Description

Time Frame

Baseline; Weeks 48, 72, 96, 144, and 192

Title

Percentage of Participants With at Least a 6% Decrease From Baseline in Spine BMD at Weeks 48, 96, 144, and 192

Description

The percentage of participants reported is the cumulative incidence from baseline to the respective time point. Data were summarized by treatment and age group (grouped by baseline age for analysis).

Time Frame

Baseline; Weeks 48, 96, 144, and 192

Title

Percentage of Participants With at Least a 6% Decrease From Baseline in Whole Body BMD at Weeks 48, 72, 96, 144, and 192

Description

The percentage of participants reported is the cumulative incidence from baseline to the respective time point. Data were summarized by treatment and age group (grouped by baseline age for analysis).

Time Frame

Baseline; Weeks 48, 72, 96, 144, and 192

Title

Percent Change From Baseline in Spine Bone Mineral Density (BMD) at Week 48

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Time Frame

Baseline; Week 48

Title

Percent Change From Baseline in Spine BMD at Week 72

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Time Frame

Baseline; Week 72

Title

Percent Change From Baseline in Spine BMD at Week 96

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Time Frame

Baseline; Week 96

Title

Percent Change From Baseline in Spine BMD at Week 144

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Time Frame

Baseline; Week 144

Title

Percent Change From Baseline in Spine BMD at Week 192

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Time Frame

Baseline; Week 192

Title

Percent Change From Baseline in Whole Body BMD at Week 48

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Time Frame

Baseline; Week 48

Title

Percent Change From Baseline in Whole Body BMD at Week 72

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Time Frame

Baseline; Week 72

Title

Percent Change From Baseline in Whole Body BMD at Week 96

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Time Frame

Baseline; Week 96

Title

Percent Change From Baseline in Whole Body BMD at Week 144

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Time Frame

Baseline; Week 144

Title

Percent Change From Baseline in Whole Body BMD at Week 192

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Time Frame

Baseline; Week 192

Title

Change From Baseline in Z-score for Spine BMD at Week 48

Description

Time Frame

Baseline; Week 48

Title

Change From Baseline in Z-score for Spine BMD at Week 72

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Time Frame

Baseline; Week 72

Title

Change From Baseline in Z-score for Spine BMD at Week 96

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Time Frame

Baseline; Week 96

Title

Change From Baseline in Z-score for Spine BMD at Week 144

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Time Frame

Baseline; Week 144

Title

Change From Baseline in Z-score for Spine BMD at Week 192

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Time Frame

Baseline; Week 192

Title

Change From Baseline in Z-score for Whole Body BMD at Week 48

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Time Frame

Baseline; Week 48

Title

Change From Baseline in Z-score for Whole Body BMD at Week 72

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Time Frame

Baseline; Week 72

Title

Change From Baseline in Z-score for Whole Body BMD at Week 96

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Time Frame

Baseline; Week 96

Title

Change From Baseline in Z-score for Whole Body BMD at Week 144

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Time Frame

Baseline; Week 144

Title

Change From Baseline in Z-score for Whole Body BMD at Week 192

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis).

Time Frame

Baseline; Week 192

Title

Number of Participants With Changes in Drug-Resistant Mutations During the Study

Description

The number of participants with changes in drug-resistant mutations during the study was summarized.

Time Frame

Baseline through Week 192

Title

Percentage of Participants Who Were HBeAg-Positive at Baseline and Who Had HBeAg Loss at Weeks 48, 72, 96, 144, and 192

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.

Time Frame

Baseline; Weeks 48, 72, 96, 144, and 192

Title

Percentage of Participants Who Were HBeAg-Positive at Baseline and Who Had HBeAg Seroconversion at Weeks 48, 72, 96, 144, and 192

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.

Time Frame

Baseline; Weeks 48, 72, 96, 144, and 192

Title

Percentage of Participants Who Were HBeAg-Positive at Baseline Who Had HBV DNA < 400 Copies/mL, Normal ALT, and HBeAg Loss/Seroconversion at Weeks 48, 72, 96, 144, and 192

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.

Time Frame

Baseline; Weeks 48, 72, 96, 144, and 192

Title

Percentage of Participants With Abnormal ALT at Baseline Who Had Normalized ALT at Weeks 48, 72, 96, 144, and 192

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.

Time Frame

Baseline; Weeks 48, 72, 96, 144, and 192

Title

Percentage of Participants With Abnormal ALT at Baseline Who Had HBV DNA < 400 Copies/mL and Normalized ALT at Weeks 48, 72, 96, 144, and 192

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.

Time Frame

Baseline; Weeks 48, 72, 96, 144, and 192

Title

Percentage of Participants Who Were HBeAg-Positive With Abnormal ALT at Baseline Who Had HBV DNA < 400 Copies/mL, Normalized ALT, and HBeAg Loss/Seroconversion at Weeks 48, 72, 96, 144, and 192

Description

Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.

Time Frame

Baseline; Weeks 48, 72, 96, 144, and 192

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Maximum Age & Unit of Time

17 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria Male or female, 12 through 17 years of age, inclusive (consent of parent/legal guardian required) Documented chronic HBV infection HBeAg positive or HBeAg negative Weight > 35 kg Able to swallow oral tablets HBV DNA > 100,000 copies/mL (polymerase chain reaction (PCR) method) Alanine aminotransferase (ALT) > 2 × upper limit of normal (ULN) at screening, OR any history of ALT > 2 × ULN over the past 24 months Willing and able to provide written informed consent/assent (child and parent/legal guardian) Negative serum pregnancy test (for postmenarchal females only) Estimated glomerular filtration rate (creatinine clearance [using the Schwartz formula]) > 80 mL/min/1.73m^2 Adequate hematologic function (absolute neutrophil count ≥ 1,500/mm^3; hemoglobin ≥ 10.0 g/dL) No prior TDF therapy (participants may have received prior interferon or oral anti-HBV nucleoside/nucleotide therapy; participants must have discontinued interferon therapy ≥ 6 months prior to screening; participants experienced on anti-HBV nucleoside/nucleotide therapy must have discontinued therapy ≥ 16 weeks prior to screening to avoid flare if randomized to the placebo arm) Exclusion Criteria Pregnant women, women who are breast feeding or who believe they may wish to become pregnant during the course of the study Males and females of reproductive potential who are not willing to use an effective method of contraception during the study Decompensated liver disease Receipt of interferon (pegylated or not) therapy within 6 months of the Screening Visit Receipt of anti-HBV nucleoside/nucleotide therapy within 16 weeks of the Screening Visit Alpha fetoprotein > 50 ng/mL Evidence of hepatocellular carcinoma (HCC) Coinfection with HIV, hepatitis C virus (HCV), or hepatitis D virus (HDV) History of significant renal disease (eg, nephrotic syndrome, renal dysgenesis, polycystic kidney disease, congenital nephrosis, acute tubular necrosis, other renal disease) History of significant bone disease (eg, osteomalacia, chronic osteomyelitis, osteogenesis imperfecta, osteochondroses, multiple bone fractures) Significant cardiovascular, pulmonary, or neurological disease Evidence of a gastrointestinal malabsorption syndrome that may interfere with absorption of orally administered medications History of solid organ or bone marrow transplantation Ongoing therapy with nephrotoxic agents, competitors of renal excretion, systemic chemotherapeutic agents, systemic corticosteroids, interleukin-2 (IL-2), or other immunomodulating or investigational agents Known hypersensitivity to the study drugs, the metabolites or formulation excipients Any other condition (including alcohol or substance abuse) or prior therapy that, in the opinion of the Investigator, would make the participants unsuitable for the study or unable to comply with dosing requirements

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Benedetta Massetto, MD, PhD

Organizational Affiliation

Gilead Sciences

Official's Role

Study Director

Facility Information:

Facility Name

Children's Hospital & Research Center at Oakland

City

Oakland

State/Province

California

ZIP/Postal Code

94609

Country

United States

Facility Name

Riley Hospital for Children

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

Facility Name

Children's Hospital & Regional Medical Center, d/b/a Seattle Children's Research Institute

City

Seattle

State/Province

Washington

ZIP/Postal Code

98105

Country

United States

Facility Name

Multiprofile Hospital for Active Treatment Sveti Georgi

City

Plovdiv

ZIP/Postal Code

4002

Country

Bulgaria

Facility Name

Clinic of Gastroenterology, Specialized Hospital for Active Treatment of Pediatric Diseases, Sofia

City

Sofia

ZIP/Postal Code

1606

Country

Bulgaria

Facility Name

Hopital Femmes Meres Enfants

City

Bron Cedex

ZIP/Postal Code

69677

Country

France

Facility Name

Hôpital Claude Huriez

City

Lille Cedex

ZIP/Postal Code

59037

Country

France

Facility Name

Samodzielny Publiczny Dzieciecy Szpital Kliniczny Akademii Medycznej w Bialymstoku

City

Białystok

ZIP/Postal Code

15-274

Country

Poland

Facility Name

Wojewodzki Specjalistyczny Szpital im Bieganskiego

City

Bydgoszcz

ZIP/Postal Code

85-030

Country

Poland

Facility Name

Wojewodzki Szpital Obserwacyjno-Zakazny im. T. Browicza

City

Bydgoszcz

ZIP/Postal Code

85-030

Country

Poland

Facility Name

Krakowski Szpital Specjalistyczny im. Jana Pawla II

City

Kraków

ZIP/Postal Code

31-202

Country

Poland

Facility Name

Samodzielny Publiczny Szpital Kliniczny im. Karola Johschera

City

Poznan

ZIP/Postal Code

60-572

Country

Poland

Facility Name

Specjalistyczny Zespol Opieki Zdrowotnej nad Matka i Dzieckiem

City

Poznań

ZIP/Postal Code

61-734

Country

Poland

Facility Name

Wojewodzki Szpital Zakazny

City

Warszawa

ZIP/Postal Code

01-201

Country

Poland

Facility Name

Samodzielny Publiczny Szpital Kliniczny Nr 1

City

Wrocław

ZIP/Postal Code

50-368

Country

Poland

Facility Name

Fundeni Clinical Institute

City

Bucharest

ZIP/Postal Code

022328

Country

Romania

Facility Name

Institute for Infectious Diseases

City

Bucharest

ZIP/Postal Code

21105

Country

Romania

Facility Name

Cluj Childrens Emergency Hospital

City

Napaco

ZIP/Postal Code

400217

Country

Romania

Facility Name

Hosp Univ y Politecnico La Fe de Valencia

City

Madrid

ZIP/Postal Code

28046

Country

Spain

Facility Name

Hospital Universitario De Getafe

City

Madrid

ZIP/Postal Code

46009

Country

Spain

Facility Name

Ege Universitesi Tip Fakultesi Hastanesi

City

Izmir

ZIP/Postal Code

35100

Country

Turkey

12. IPD Sharing Statement

Citations:

PubMed Identifier

22544804

Citation

Murray KF, Szenborn L, Wysocki J, Rossi S, Corsa AC, Dinh P, McHutchison J, Pang PS, Luminos LM, Pawlowska M, Mizerski J. Randomized, placebo-controlled trial of tenofovir disoproxil fumarate in adolescents with chronic hepatitis B. Hepatology. 2012 Dec;56(6):2018-26. doi: 10.1002/hep.25818. Epub 2012 Aug 27.

Results Reference

result

Learn more about this trial

Evaluation of Tenofovir Disoproxil Fumarate in Adolescents With Chronic Hepatitis B Infection

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