N/A
- Registration Number
- 2024-517526-26-00
- Lead Sponsor
- Gilead Sciences Inc., Gilead Sciences Inc.
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ended
- Sex
- Not specified
- Target Recruitment
- 23
Male or Female, 2 to < 12 years of age
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)
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
Pregnant or lactating
Long term non-steroidal, anti-inflammatory drug therapy Note: Other protocol defined Inclusion/Exclusion criteria may apply
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tenofovir DF (Blinded Randomized Treatment) Tenofovir DF Participants will receive tenofovir disoproxil fumarate (tenofovir DF; TDF) for 72 weeks (protocol amendment 2) or 48 weeks (protocol amendment 3). Placebo to match TDF (Blinded Randomized Treatment) TDF Placebo Participants will receive TDF placebo for 72 weeks (protocol amendment 2) or 48 weeks (protocol amendment 3). Tenofovir DF (Open-label Extension Phase) Tenofovir DF Following the completion of study at Week 192, participants may have the option to receive open-label TDF until it is commercially available in that country for treatment of chronic HBV in participants of their age and weight. Tenofovir DF (Open-label Treatment) Tenofovir DF Following 72 weeks (protocol amendment 2) or 48 weeks (protocol amendment 3) of blinded randomized treatment, participants will switch to open-label TDF treatment for an additional 120 weeks (protocol amendment 2) or 144 weeks (protocol amendment 3).
- Primary Outcome Measures
Name Time Method 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 = 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] Percentage of Participants With Serum HBV DNA < 400 Copies/mL (69 IU/mL) at Week 48 (Missing = Excluded Approach) [Time Frame: Week 48]
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Hepatitis B e Antigen (HBeAg) Seroconversion at Week 48 [Time Frame: Week 48] HBeAg seroconversion was defined as HBeAg loss and a change from HBeAb negative or missing at baseline to HBeAb positive. Percentage of Participants With Hepatitis B e Antigen (HBeAg) Seroconversion at Week 48 [Time Frame: Week 48] HBeAg seroconversion was defined as HBeAg loss and a change from HBeAb negative or missing at baseline to HBeAb positive.
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 [Time Frame: Week 48] Normal ALT was defined as ≤ 30 U/L for males and females 0-12 years based on the AASLD pediatric normal range. 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 [Time Frame: Week 48] Normal ALT was defined as ≤ 30 U/L for males and females 0-12 years based on the AASLD pediatric normal range.
Percentage of Participants With Normal ALT at Week 192, Based on the AASLD Normal Range [Time Frame: Week 192] Normal ALT was defined as ≤ 30 U/L for males and females 0-12 years based on the AASLD pediatric normal range. Percentage of Participants With Normal ALT at Week 192, Based on the AASLD Normal Range [Time Frame: Week 192] Normal ALT was defined as ≤ 30 U/L for males and females 0-12 years based on the AASLD pediatric normal range.
Percentage of Participants With Normal ALT at Week 48, Based on the Central Lab Normal Range [Time Frame: Week 48] 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. Percentage of Participants With Normal ALT at Week 48, Based on the Central Lab Normal Range [Time Frame: Week 48] 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.
Percentage of Participants With Normal ALT at Week 192, Based on the Central Lab Normal Range [Time Frame: Week 192] 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. Percentage of Participants With Normal ALT at Week 192, Based on the Central Lab Normal Range [Time Frame: Week 192] 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.
Percentage of Participants With Normalized ALT at Week 48, Based on the AASLD Normal Range [Time Frame: Week 48] 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. Percentage of Participants With Normalized ALT at Week 48, Based on the AASLD Normal Range [Time Frame: Week 48] 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.
Percentage of Participants With Normalized ALT at Week 192, Based on the AASLD Normal Range [Time Frame: Week 192] 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. Percentage of Participants With Normalized ALT at Week 192, Based on the AASLD Normal Range [Time Frame: Week 192] 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.
Percentage of Participants With Normalized ALT at Week 48, Based on the Central Lab Normal Range [Time Frame: Week 48] 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. Percentage of Participants With Normalized ALT at Week 48, Based on the Central Lab Normal Range [Time Frame: Week 48] 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.
Percentage of Participants With Normalized ALT at Week 192, Based on the Central Lab Normal Range [Time Frame: Week 192] 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. Percentage of Participants With Normalized ALT at Week 192, Based on the Central Lab Normal Range [Time Frame: Week 192] 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.
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] 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. 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] 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.
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] 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. 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] 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.
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 48 [Time Frame: Week 48]
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. 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.
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] 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 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 HBV DNA < 169 Copies/mL (29 IU/mL) at Week 192 [Time Frame: Week 192]
Percentage of Participants With HBsAg Loss at Week 48 [Time Frame: Week 48] HBsAg Loss was defined as a change from HBsAg positive or missing at baseline to HBsAg negative. Percentage of Participants With HBsAg Loss at Week 48 [Time Frame: Week 48] HBsAg Loss was defined as a change from HBsAg positive or missing at baseline to HBsAg negative.
Percentage of Participants With HBsAg Loss at Week 192 [Time Frame: Week 192] HBsAg Loss was defined as a change from HBsAg positive or missing at baseline to HBsAg negative. Percentage of Participants With HBsAg Loss at Week 192 [Time Frame: Week 192] HBsAg Loss was defined as a change from HBsAg positive or missing at baseline to HBsAg negative.
Percentage of Participants With HBsAg Seroconversion at Week 48 [Time Frame: Week 48] HBsAg seroconversion was defined as HBsAg loss and a change from HBsAb negative or missing at baseline to HBsAb positive. Percentage of Participants With HBsAg Seroconversion at Week 48 [Time Frame: Week 48] HBsAg seroconversion was defined as HBsAg loss and a change from HBsAb negative or missing at baseline to HBsAb positive.
Percentage of Participants With HBsAg Seroconversion at Week 192 [Time Frame: Week 192] HBsAg seroconversion was defined as HBsAg loss and a change from HBsAb negative or missing at baseline to HBsAb positive. Percentage of Participants With HBsAg Seroconversion at Week 192 [Time Frame: Week 192] HBsAg seroconversion was defined as HBsAg loss and a change from HBsAb negative or missing at baseline to HBsAb positive.
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] 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]
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 [Time Frame: Baseline; Week 96] 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 [Time Frame: Baseline; Week 96]
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 [Time Frame: Baseline; Week 144] 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 [Time Frame: Baseline; Week 144]
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 [Time Frame: Baseline; 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 192 [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 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] 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 48 [Time Frame: Baseline; Week 48]
Percent Change From Baseline in BMD of Spine at Week 192 [Time Frame: Baseline; Week 192] Percent Change From Baseline in BMD of Spine at Week 192 [Time Frame: Baseline; Week 192]
Trial Locations
- Locations (2)
Spitalul Clinic De Boli Infectioase Si Pneumoftiziologie Victor Babes Craiova
🇷🇴Craiova, Romania
Spitalul Clinic De Urgenta Pentru Copii Grigore Alexandrescu
🇷🇴Bucharest, Romania
Spitalul Clinic De Boli Infectioase Si Pneumoftiziologie Victor Babes Craiova🇷🇴Craiova, RomaniaGheorghe Iulian DiaconescuSite contact+40721334400diaconescu_ig@yahoo.com