Clinical trial NCT01651403: Study to Evaluate the Antiviral Efficacy, Safety and Tolerability of Tenofovir Disoproxil Fumarate Versus Placebo in Pediatric Participants 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 Pediatric Patients With Chronic Hepatitis B Infection
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Chronic Hepatitis B
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2012-07-27
Enrollment: 90
Sex: ALL
Minimum age (years): 2
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With Serum HBV DNA < 400 Copies/mL (69 IU/mL) at Week 48 (Missing = Failure Approach)
timeFrame: Week 48
measure: Percentage of Participants With Serum HBV DNA < 400 Copies/mL (69 IU/mL) at Week 48 (Missing = Excluded Approach)
timeFrame: Week 48
Secondary outcomes:
measure: Percentage of Participants With Hepatitis B e Antigen (HBeAg) Seroconversion at Week 48
timeFrame: Week 48
measure: 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
timeFrame: Week 48
measure: Percentage of Participants With Normal ALT at Week 192, Based on the AASLD Normal Range
timeFrame: Week 192
measure: Percentage of Participants With Normal ALT at Week 48, Based on the Central Lab Normal Range
timeFrame: Week 48
measure: Percentage of Participants With Normal ALT at Week 192, Based on the Central Lab Normal Range
timeFrame: Week 192
measure: Percentage of Participants With Normalized ALT at Week 48, Based on the AASLD Normal Range
timeFrame: Week 48
measure: Percentage of Participants With Normalized ALT at Week 192, Based on the AASLD Normal Range
timeFrame: Week 192
measure: Percentage of Participants With Normalized ALT at Week 48, Based on the Central Lab Normal Range
timeFrame: Week 48
measure: Percentage of Participants With Normalized ALT at Week 192, Based on the Central Lab Normal Range
timeFrame: Week 192
measure: 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
timeFrame: Week 48
measure: 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
timeFrame: Week 192
measure: 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
timeFrame: Week 48
measure: 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
timeFrame: Week 192
measure: Percentage of Participants With HBV DNA < 169 Copies/mL (29 IU/mL) at Week 48
timeFrame: Week 48
measure: Percentage of Participants With HBV DNA < 169 Copies/mL (29 IU/mL) at Week 192
timeFrame: Week 192
measure: Percentage of Participants With HBsAg Loss at Week 48
timeFrame: Week 48
measure: Percentage of Participants With HBsAg Loss at Week 192
timeFrame: Week 192
measure: Percentage of Participants With HBsAg Seroconversion at Week 48
timeFrame: Week 48
measure: Percentage of Participants With HBsAg Seroconversion at Week 192
timeFrame: Week 192
measure: 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
timeFrame: Baseline; Week 48
measure: 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 96
timeFrame: Baseline; Week 96
measure: 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 144
timeFrame: Baseline; Week 144
measure: 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 192
timeFrame: Baseline; Week 192
measure: Percentage of Participants With ≥ 4% Decrease From Baseline in Spine Bone Mineral Density (BMD) at Week 48
timeFrame: Baseline; Week 48
measure: Percentage of Participants With ≥ 4% Decrease From Baseline in Spine BMD at Week 192
timeFrame: Baseline; Week 192
measure: Percent Change From Baseline in BMD of Spine at Week 48
timeFrame: Baseline; Week 48
measure: Percent Change From Baseline in BMD of Spine at Week 192
timeFrame: Baseline; Week 192
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Surat
country: India
facility: Nirmal Hospital Private Limited
state: Gujrat
city: Gurgaon
country: India
facility: Medanta -The Medicity
state: Haryana
city: Nagpur
country: India
facility: Colors Children Hospital
state: Maharashtra
city: Jaipur
country: India
facility: SMS Medical College and Hospital
state: Rajasthan
city: Lucknow
country: India
facility: M.V. Hospital and Research Centre 314/30 Mirza Mandi Chowk
state: Uttar Pradesh
city: Bangalore
country: India
facility: St. John Hospital & Medical Center
city: Yangsan
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
state: Gyeongnam
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Children's Hospital
city: Bucharest
country: Romania
facility: Grigore Alexandrescu Emergency Clinical Hospital for Children
city: Bucharest
country: Romania
facility: Fundeni Clinical Institute - Constantinesco
city: Craiova
country: Romania
facility: Victor Babes Clinical Hospital of Infectious Diseases and Pneumophtisology
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: (Oral Presentation) Mei-Hwei Chang, Jae Hong Park, Jorge A. Bezerra, Daniela Pacura, Sandeep Nijhawan, Byung-Ho Choe, et al. Randomized, Double-Blind, Placebo-Controlled Trial of Tenofovir Disoproxil Fumarate (TDF) in Children with Chronic Hepatitis B (CHB). Hepatology, 2018; 68 (Suppl 1): 49A.