Study to Evaluate the Antiviral Efficacy, Safety and Tolerability of Tenofovir Disoproxil Fumarate Versus Placebo in Pediatric Participants With Chronic Hepatitis B Infection

Phase 3Active Not RecruitingNCT01651403

Gilead Sciences90 enrolled

Overview

The primary objective of this study is to evaluate the antiviral efficacy of tenofovir disoproxil fumarate (tenofovir DF; TDF) versus placebo in pediatric population (aged 2 to \< 12 years at the time of enrollment) with chronic hepatitis B (CHB) infection.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Chronic Hepatitis B

Interventions

Tenofovir DFDRUG

* Participants weighing ≥ 17 kg will receive TDF one tablet administered orally once daily (150, 200, 250 or 300 mg tablets based on body weight). * Participants weighing \< 17 kg or ≥ 17 kg who are unable to swallow a tablet will receive TDF oral powder in a dose of 8 mg/kg once daily up to a maximum dose of 300 mg.

TDF PlaceboDRUG

* Participants weighing ≥ 17 kg will receive TDF placebo tablet administered orally once daily. * Participants weighing \< 17 kg or ≥ 17 kg who are unable to swallow a tablet will receive TDF placebo oral powder once daily.

Eligibility

Sex: ALLMin age: 2 YearsMax age: 11 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Male or Female, 2 to \< 12 years of age * Weight ≥ 10 kg * Chronic HBV infection ≥ 6 months * Hepatitis B e antigen (HBeAg)-positive or HBeAg-negative * HBV Viral Load ≥ 100,000 copies/mL * Alanine aminotransferase (ALT) ≥ 1.5 x the upper limit of the normal range (ULN) at screening * Creatinine Clearance ≥ 80 mL/min/1.73m\^2 * Absolute neutrophil count (ANC) ≥ 1,500/mm\^3, hemoglobin ≥ 10 g/dL * Negative pregnancy test at screening * No prior tenofovir DF therapy (participants may have received prior interferon-alfa and/or other oral anti-HBV nucleoside/nucleotide therapy; participants must have discontinued interferon-alfa therapy ≥ 6 months prior to screening; participants experienced on other anti-HBV nucleoside/nucleotide therapy must have discontinued therapy ≥ 16 weeks prior to screening to avoid flare if randomized to the placebo arm) Key Exclusion Criteria: * Pregnant or lactating * Decompensated liver disease * Received interferon therapy within 6 months of screening * Received anti-HBV nucleoside/nucleotide therapy within 16 weeks of screening * Alpha-fetoprotein levels \> 50 ng/mL * Evidence of hepatocellular carcinoma (HCC) * Co-infection with human immunodeficiency virus (HIV), acute hepatitis A virus (HAV), hepatitis C virus (HCV), or hepatitis D virus (HDV) * Chronic liver disease not due to HBV * History of significant renal, cardiovascular, pulmonary, neurological or bone disease * Long term non-steroidal, anti-inflammatory drug therapy Note: Other protocol defined Inclusion/Exclusion criteria may apply

Locations (21)

Phoenix Children's Hospital

Phoenix, Arizona, United States

Outcomes

Primary Outcomes

Percentage of Participants With Serum HBV DNA < 400 Copies/mL (69 IU/mL) at Week 48 (Missing = Failure Approach)

Time frame: Week 48

Percentage of Participants With Serum HBV DNA < 400 Copies/mL (69 IU/mL) at Week 48 (Missing = Excluded Approach)

Time frame: Week 48

Secondary Outcomes

Percentage of Participants With Hepatitis B e Antigen (HBeAg) Seroconversion at Week 48

HBeAg seroconversion was defined as HBeAg loss and a change from HBeAb negative or missing at baseline to HBeAb positive.

Time frame: Week 48

Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Week 48, Based on the American Association for the Study of Liver Diseases (AASLD) Normal Range

Normal ALT was defined as ≤ 30 U/L for males and females 0-12 years based on the AASLD pediatric normal range.

Time frame: Week 48

Percentage of Participants With Normal ALT at Week 192, Based on the AASLD Normal Range

Normal ALT was defined as ≤ 30 U/L for males and females 0-12 years based on the AASLD pediatric normal range.

Time frame: Week 192

Percentage of Participants With Normal ALT at Week 48, Based on the Central Lab Normal Range

Normal ALT was defined as ≤ 34 U/L for females aged 2-15 years old or males aged 1-9 years old, and ≤ 43 U/L for males aged 10-15 years old based on the central lab normal range.

Time frame: Week 48

Percentage of Participants With Normal ALT at Week 192, Based on the Central Lab Normal Range

Normal ALT was defined as ≤ 34 U/L for females aged 2-15 years old or males aged 1-9 years old, and ≤ 43 U/L for males aged 10-15 years old based on the central lab normal range.

Data from ClinicalTrials.gov

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University of California, San Francisco

San Francisco, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Texas Children's Hospital

Houston, Texas, United States

Nirmal Hospital Private Limited

Surat, Gujarat, India

Medanta -The Medicity

Gurgaon, Haryana, India

Colors Children Hospital

Nagpur, Maharashtra, India

SMS Medical College and Hospital

Jaipur, Rajasthan, India

M.V. Hospital and Research Centre 314/30 Mirza Mandi Chowk

Lucknow, Uttar Pradesh, India

...and 11 more locations

Time frame: Week 192

Percentage of Participants With Normalized ALT at Week 48, Based on the AASLD Normal Range

Normal ALT was defined as ≤ 30 U/L for males and females 0-12 years based on the AASLD pediatric normal range. ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit.

Time frame: Week 48

Percentage of Participants With Normalized ALT at Week 192, Based on the AASLD Normal Range

Time frame: Week 192

Percentage of Participants With Normalized ALT at Week 48, Based on the Central Lab Normal Range

Normal ALT was defined as ≤ 34 U/L for females aged 2-15 years old or males aged 1-9 years old, and ≤ 43 U/L for males aged 10-15 years old based on the central lab normal range. ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit.

Time frame: Week 48

Percentage of Participants With Normalized ALT at Week 192, Based on the Central Lab Normal Range

Time frame: Week 192

Composite Endpoint of Percentage of Participants With HBV DNA < 400 Copies/mL (69 IU/mL) and Normalized ALT (Based on AASLD Normal Range) at Week 48

Time frame: Week 48

Composite Endpoint of Percentage of Participants With HBV DNA < 400 Copies/mL (69 IU/mL) and Normalized ALT (Based on AASLD Normal Range) at Week 192

Time frame: Week 192

Composite Endpoint of Percentage of Participants With HBV DNA < 400 Copies/mL (69 IU/mL) and Normalized ALT (Based on Central Lab Normal Range) at Week 48

Time frame: Week 48

Composite Endpoint of Percentage of Participants With HBV DNA < 400 Copies/mL (69 IU/mL) and Normalized ALT (Based on Central Lab Normal Range) at Week 192

Time frame: Week 192

Percentage of Participants With HBV DNA < 169 Copies/mL (29 IU/mL) at Week 48

Time frame: Week 48

Percentage of Participants With HBV DNA < 169 Copies/mL (29 IU/mL) at Week 192

Time frame: Week 192

Percentage of Participants With HBsAg Loss at Week 48

HBsAg Loss was defined as a change from HBsAg positive or missing at baseline to HBsAg negative.

Time frame: Week 48

Percentage of Participants With HBsAg Loss at Week 192

HBsAg Loss was defined as a change from HBsAg positive or missing at baseline to HBsAg negative.

Time frame: Week 192

Percentage of Participants With HBsAg Seroconversion at Week 48

HBsAg seroconversion was defined as HBsAg loss and a change from HBsAb negative or missing at baseline to HBsAb positive.

Time frame: Week 48

Percentage of Participants With HBsAg Seroconversion at Week 192

HBsAg seroconversion was defined as HBsAg loss and a change from HBsAb negative or missing at baseline to HBsAb positive.

Time frame: Week 192

Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase for Participants Who Were Viremic (HBV DNA ≥ 400 Copies/mL [69 IU/mL]) Including Participants With Confirmed Virologic Breakthrough at Week 48

Time frame: Baseline; Week 48

Time frame: Baseline; Week 96

Time frame: Baseline; Week 144

Time frame: Baseline; Week 192

Percentage of Participants With ≥ 4% Decrease From Baseline in Spine Bone Mineral Density (BMD) at Week 48

Time frame: Baseline; Week 48

Percentage of Participants With ≥ 4% Decrease From Baseline in Spine BMD at Week 192

Time frame: Baseline; Week 192

Percent Change From Baseline in BMD of Spine at Week 48

Time frame: Baseline; Week 48

Percent Change From Baseline in BMD of Spine at Week 192

Time frame: Baseline; Week 192