Chronic Hepatitis B
Conditions
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.
Interventions
DRUGTenofovir DF
* 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.
DRUGTDF Placebo
* 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.
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Years to 11 Years
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Serum HBV DNA < 400 Copies/mL (69 IU/mL) at Week 48 (Missing = Failure Approach) | Week 48 |
| Percentage of Participants With Serum HBV DNA < 400 Copies/mL (69 IU/mL) at Week 48 (Missing = Excluded Approach) | Week 48 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Hepatitis B e Antigen (HBeAg) Seroconversion at Week 48 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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. |
| 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 | 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 HBV DNA < 169 Copies/mL (29 IU/mL) at Week 48 | Week 48 | — |
| Percentage of Participants With HBV DNA < 169 Copies/mL (29 IU/mL) at Week 192 | Week 192 | — |
| Percentage of Participants With HBsAg Loss at Week 48 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | Baseline; Week 192 | — |
| Percentage of Participants With ≥ 4% Decrease From Baseline in Spine Bone Mineral Density (BMD) at Week 48 | Baseline; Week 48 | — |
| Percentage of Participants With ≥ 4% Decrease From Baseline in Spine BMD at Week 192 | Baseline; Week 192 | — |
| Percent Change From Baseline in BMD of Spine at Week 48 | Baseline; Week 48 | — |
| Percent Change From Baseline in BMD of Spine at Week 192 | Baseline; Week 192 | — |
Countries
India, Romania, South Korea, Taiwan, United States
Contacts
STUDY_DIRECTORGilead Study Director
Gilead Sciences
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States, Asia, and Europe.The first participant was screened on 06 December 2012. The last Week 192 study visit occurred on 02 June 2020.
Pre-assignment details
176 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Tenofovir Disoproxil Fumarate Blinded Randomized Phase: TDF tablet or oral powder once daily (up to 300 mg depending on weight) for 72 weeks (protocol amendment 2) or 48 weeks (protocol amendment 3)
Open-Label Treatment Phase: After Week 72 (protocol amendment 2) or Week 48 (protocol amendment 3), participants switched to open-label TDF treatment for an additional 120 weeks (protocol amendment 2) or 144 weeks (protocol amendment 3).
Open-Label Extension Phase: After Week 192, participants are offered open-label TDF treatment until it was commercially available in that country for treatment of chronic HBV in individuals of their age and weight. | 60 |
| Placebo Blinded Randomized Phase: Placebo tablet or oral powder once daily for 72 weeks (protocol amendment 2) or 48 weeks (protocol amendment 3)
Open-Label Treatment Phase: After Week 72 (protocol amendment 2) or Week 48 (protocol amendment 3), participants switched to open-label TDF treatment for an additional 120 weeks (protocol amendment 2) or 144 weeks (protocol amendment 3).
Open-Label Extension Phase: After Week 192, participants are offered open-label TDF treatment until it was commercially available in that country for treatment of chronic HBV in individuals of their age and weight. | 29 |
| Total | 89 |
Baseline characteristics
| Characteristic | Tenofovir Disoproxil Fumarate | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 6 years STANDARD_DEVIATION 2.5 | 7 years STANDARD_DEVIATION 3.2 | 6 years STANDARD_DEVIATION 2.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 60 Participants | 29 Participants | 89 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| HBeAb Negative or Missing | 56 Participants | 29 Participants | 85 Participants |
| HBeAb Positive | 4 Participants | 0 Participants | 4 Participants |
| HBV DNA | 8.089 log10 IU/mL STANDARD_DEVIATION 0.7208 | 8.133 log10 IU/mL STANDARD_DEVIATION 1.2538 | 8.103 log10 IU/mL STANDARD_DEVIATION 0.9214 |
| Hepatitis B e antigen (HBeAg) Negative | 4 Participants | 0 Participants | 4 Participants |
| Hepatitis B e antigen (HBeAg) Positive | 56 Participants | 29 Participants | 85 Participants |
| Hepatitis B Virus Surface Antigen (HBsAg) Negative | 0 Participants | 0 Participants | 0 Participants |
| Hepatitis B Virus Surface Antigen (HBsAg) Positive | 60 Participants | 29 Participants | 89 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 41 Participants | 17 Participants | 58 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 11 Participants | 26 Participants |
| Region of Enrollment India | 8 Participants | 5 Participants | 13 Participants |
| Region of Enrollment Romania | 13 Participants | 10 Participants | 23 Participants |
| Region of Enrollment South Korea | 23 Participants | 11 Participants | 34 Participants |
| Region of Enrollment Taiwan | 2 Participants | 0 Participants | 2 Participants |
| Region of Enrollment United States | 14 Participants | 3 Participants | 17 Participants |
| Sex: Female, Male Female | 27 Participants | 12 Participants | 39 Participants |
| Sex: Female, Male Male | 33 Participants | 17 Participants | 50 Participants |
| Spine Bone Mineral Density | 0.586 g/cm^2 STANDARD_DEVIATION 0.1196 | 0.626 g/cm^2 STANDARD_DEVIATION 0.1567 | 0.599 g/cm^2 STANDARD_DEVIATION 0.1332 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 60 | 0 / 30 | 0 / 56 | 0 / 25 |
| other Total, other adverse events | 38 / 60 | 16 / 29 | 21 / 56 | 7 / 25 |
| serious Total, serious adverse events | 10 / 60 | 2 / 29 | 8 / 56 | 3 / 25 |
Outcome results
Primary
Percentage of Participants With Serum HBV DNA < 400 Copies/mL (69 IU/mL) at Week 48 (Missing = Excluded Approach)
Time frame: Week 48
Population: Participants in the Full Analysis Set with available data were analyzed. The missing equals failure approach was used where all participants with missing data were excluded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF (Blinded Randomized Phase) | Percentage of Participants With Serum HBV DNA < 400 Copies/mL (69 IU/mL) at Week 48 (Missing = Excluded Approach) | 83.6 percentage of participants |
| Placebo (Blinded Randomized Phase) | Percentage of Participants With Serum HBV DNA < 400 Copies/mL (69 IU/mL) at Week 48 (Missing = Excluded Approach) | 7.7 percentage of participants |
p-value: <0.001Cochran-Mantel-Haenszel
Primary
Percentage of Participants With Serum HBV DNA < 400 Copies/mL (69 IU/mL) at Week 48 (Missing = Failure Approach)
Time frame: Week 48
Population: The Full Analysis Set (FAS) included randomized participants who have received at least 1 dose of study drug. Participants will be analyzed according to the treatment to which they were randomized. The missing equals failure approach was used where all participants with missing data were considered to have failed to achieve the endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF (Blinded Randomized Phase) | Percentage of Participants With Serum HBV DNA < 400 Copies/mL (69 IU/mL) at Week 48 (Missing = Failure Approach) | 76.7 percentage of participants |
| Placebo (Blinded Randomized Phase) | Percentage of Participants With Serum HBV DNA < 400 Copies/mL (69 IU/mL) at Week 48 (Missing = Failure Approach) | 6.9 percentage of participants |
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Fisher Exact
Secondary
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
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 192
Population: Participants in the Full Analysis Set with abnormal ALT values at baseline were analyzed. The missing equals failure approach was used where all participants with missing data were considered to have failed to reach the endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF (Blinded Randomized Phase) | 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 | 70.0 percentage of participants |
| Placebo (Blinded Randomized Phase) | 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 | 42.9 percentage of participants |
Secondary
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
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
Population: Participants in the Full Analysis Set with abnormal ALT values at baseline were analyzed. The missing equals failure approach was used where all participants with missing data were considered to have failed to reach the endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF (Blinded Randomized Phase) | 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 | 46.7 percentage of participants |
| Placebo (Blinded Randomized Phase) | 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 | 7.1 percentage of participants |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
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
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 192
Population: Participants in the Full Analysis Set with abnormal ALT values at baseline were analyzed. The missing equals failure approach was used where all participants with missing data were considered to have failed to reach the endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF (Blinded Randomized Phase) | 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 | 75.9 percentage of participants |
| Placebo (Blinded Randomized Phase) | 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 | 55.6 percentage of participants |
Secondary
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
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
Population: Participants in the Full Analysis Set with abnormal ALT values at baseline were analyzed. The missing equals failure approach was used where all participants with missing data were considered to have failed to reach the endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF (Blinded Randomized Phase) | 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 | 53.4 percentage of participants |
| Placebo (Blinded Randomized Phase) | 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 | 7.4 percentage of participants |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
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
Population: Participants in the Full Analysis Set with serum samples available at baseline and with HBV DNA ≥ 69 IU/mL at Week 144 were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TDF (Blinded Randomized Phase) | 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 | 1 Participants |
| Placebo (Blinded Randomized Phase) | 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 | 0 Participants |
Secondary
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
Population: Participants in the Full Analysis Set with serum samples available at baseline and with HBV DNA ≥ 69 IU/mL at Week 192 were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TDF (Blinded Randomized Phase) | 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 | 0 Participants |
| Placebo (Blinded Randomized Phase) | 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 | 0 Participants |
Secondary
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
Population: Participants in the Full Analysis Set with serum samples available at baseline and with HBV DNA ≥ 69 IU/mL at Week 48 were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TDF (Blinded Randomized Phase) | 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 | 5 Participants |
| Placebo (Blinded Randomized Phase) | 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 | 7 Participants |
Secondary
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
Population: Participants in the Full Analysis Set with serum samples available at baseline and with HBV DNA ≥ 69 IU/mL at Week 96 were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TDF (Blinded Randomized Phase) | 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 | 1 Participants |
| Placebo (Blinded Randomized Phase) | 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 | 2 Participants |
Secondary
Percentage of Participants With ≥ 4% Decrease From Baseline in Spine BMD at Week 192
Time frame: Baseline; Week 192
Population: Participants in the Spine DXA Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF (Blinded Randomized Phase) | Percentage of Participants With ≥ 4% Decrease From Baseline in Spine BMD at Week 192 | 18.3 percentage of participants |
| Placebo (Blinded Randomized Phase) | Percentage of Participants With ≥ 4% Decrease From Baseline in Spine BMD at Week 192 | 6.9 percentage of participants |
95% CI: [-6.9, 25.1]
Secondary
Percentage of Participants With ≥ 4% Decrease From Baseline in Spine Bone Mineral Density (BMD) at Week 48
Time frame: Baseline; Week 48
Population: Spine Dual X-Ray Absorptiometry (DXA) Analysis Set: all randomized participants who received at least 1 dose of study drug and had nonmissing baseline spine bone mineral density values.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF (Blinded Randomized Phase) | Percentage of Participants With ≥ 4% Decrease From Baseline in Spine Bone Mineral Density (BMD) at Week 48 | 18.3 percentage of participants |
| Placebo (Blinded Randomized Phase) | Percentage of Participants With ≥ 4% Decrease From Baseline in Spine Bone Mineral Density (BMD) at Week 48 | 6.9 percentage of participants |
95% CI: [-6.9, 25.1]
Secondary
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
Population: Serologically Evaluable Full Analysis Set For HBsAg Loss/Seroconversion; The missing equals failure approach was used where all participants with missing data were considered to have failed to reach the endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF (Blinded Randomized Phase) | Percentage of Participants With HBsAg Loss at Week 192 | 10.0 percentage of participants |
| Placebo (Blinded Randomized Phase) | Percentage of Participants With HBsAg Loss at Week 192 | 0 percentage of participants |
Secondary
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
Population: Serologically Evaluable Full Analysis Set For HBsAg Loss/Seroconversion; The missing equals failure approach was used where all participants with missing data were considered to have failed to reach the endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF (Blinded Randomized Phase) | Percentage of Participants With HBsAg Loss at Week 48 | 3.3 percentage of participants |
| Placebo (Blinded Randomized Phase) | Percentage of Participants With HBsAg Loss at Week 48 | 3.4 percentage of participants |
p-value: >0.999Cochran-Mantel-Haenszel
Secondary
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
Population: Serologically Evaluable Full Analysis Set For HBsAg Loss/Seroconversion; The missing equals failure approach was used where all participants with missing data were considered to have failed to reach the endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF (Blinded Randomized Phase) | Percentage of Participants With HBsAg Seroconversion at Week 192 | 0 percentage of participants |
| Placebo (Blinded Randomized Phase) | Percentage of Participants With HBsAg Seroconversion at Week 192 | 0 percentage of participants |
Secondary
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
Population: Serologically Evaluable Full Analysis Set For HBsAg Loss/Seroconversion; The missing equals failure approach was used where all participants with missing data were considered to have failed to reach the endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF (Blinded Randomized Phase) | Percentage of Participants With HBsAg Seroconversion at Week 48 | 0 percentage of participants |
| Placebo (Blinded Randomized Phase) | Percentage of Participants With HBsAg Seroconversion at Week 48 | 0 percentage of participants |
Secondary
Percentage of Participants With HBV DNA < 169 Copies/mL (29 IU/mL) at Week 192
Time frame: Week 192
Population: Participants in the Full Analysis Set were analyzed. The missing equals failure approach was used where all participants with missing data were considered to have failed to reach the endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF (Blinded Randomized Phase) | Percentage of Participants With HBV DNA < 169 Copies/mL (29 IU/mL) at Week 192 | 81.7 percentage of participants |
| Placebo (Blinded Randomized Phase) | Percentage of Participants With HBV DNA < 169 Copies/mL (29 IU/mL) at Week 192 | 62.1 percentage of participants |
Secondary
Percentage of Participants With HBV DNA < 169 Copies/mL (29 IU/mL) at Week 48
Time frame: Week 48
Population: Participants in the Full Analysis Set were analyzed. The missing equals failure approach was used where all participants with missing data were considered to have failed to reach the endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF (Blinded Randomized Phase) | Percentage of Participants With HBV DNA < 169 Copies/mL (29 IU/mL) at Week 48 | 71.7 percentage of participants |
| Placebo (Blinded Randomized Phase) | Percentage of Participants With HBV DNA < 169 Copies/mL (29 IU/mL) at Week 48 | 6.9 percentage of participants |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
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
Population: Serologically Evaluable FAS For HBeAg loss/seroconversion: participants who were randomized and had received at least 1 dose of study drug, and with HBeAg positive and HBeAb negative or missing at baseline. The missing equals failure approach was used where all participants with missing data were considered to have failed to reach the endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF (Blinded Randomized Phase) | Percentage of Participants With Hepatitis B e Antigen (HBeAg) Seroconversion at Week 48 | 25.0 percentage of participants |
| Placebo (Blinded Randomized Phase) | Percentage of Participants With Hepatitis B e Antigen (HBeAg) Seroconversion at Week 48 | 24.1 percentage of participants |
p-value: 0.935Cochran-Mantel-Haenszel
Secondary
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
Population: Participants in the Full Analysis Set were analyzed. The missing equals failure approach was used where all participants with missing data were considered to have failed to reach the endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF (Blinded Randomized Phase) | 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 | 51.7 percentage of participants |
| Placebo (Blinded Randomized Phase) | 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 | 17.2 percentage of participants |
p-value: 0.001Cochran-Mantel-Haenszel
Secondary
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
Population: Participants in the Full Analysis Set were analyzed. The missing equals failure approach was used where all participants with missing data were considered to have failed to reach the endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF (Blinded Randomized Phase) | Percentage of Participants With Normal ALT at Week 192, Based on the AASLD Normal Range | 71.7 percentage of participants |
| Placebo (Blinded Randomized Phase) | Percentage of Participants With Normal ALT at Week 192, Based on the AASLD Normal Range | 51.7 percentage of participants |
Secondary
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.
Time frame: Week 192
Population: Participants in the Full Analysis Set were analyzed. The missing equals failure approach was used where all participants with missing data were considered to have failed to reach the endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF (Blinded Randomized Phase) | Percentage of Participants With Normal ALT at Week 192, Based on the Central Lab Normal Range | 80.0 percentage of participants |
| Placebo (Blinded Randomized Phase) | Percentage of Participants With Normal ALT at Week 192, Based on the Central Lab Normal Range | 62.1 percentage of participants |
Secondary
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
Population: Participants in the Full Analysis Set were analyzed. The missing equals failure approach was used where all participants with missing data were considered to have failed to reach the endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF (Blinded Randomized Phase) | Percentage of Participants With Normal ALT at Week 48, Based on the Central Lab Normal Range | 65.0 percentage of participants |
| Placebo (Blinded Randomized Phase) | Percentage of Participants With Normal ALT at Week 48, Based on the Central Lab Normal Range | 17.2 percentage of participants |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Normalized 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. 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 192
Population: Participants in the Full Analysis Set with abnormal ALT values at baseline were analyzed. The missing equals failure approach was used where all participants with missing data were considered to have failed to reach the endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF (Blinded Randomized Phase) | Percentage of Participants With Normalized ALT at Week 192, Based on the AASLD Normal Range | 71.7 percentage of participants |
| Placebo (Blinded Randomized Phase) | Percentage of Participants With Normalized ALT at Week 192, Based on the AASLD Normal Range | 50.0 percentage of participants |
Secondary
Percentage of Participants With Normalized 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. 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 192
Population: Participants in the Full Analysis Set with abnormal ALT values at baseline were analyzed. The missing equals failure approach was used where all participants with missing data were considered to have failed to reach the endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF (Blinded Randomized Phase) | Percentage of Participants With Normalized ALT at Week 192, Based on the Central Lab Normal Range | 79.3 percentage of participants |
| Placebo (Blinded Randomized Phase) | Percentage of Participants With Normalized ALT at Week 192, Based on the Central Lab Normal Range | 59.3 percentage of participants |
Secondary
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
Population: Participants in the Full Analysis Set with abnormal ALT values at baseline were analyzed. The missing equals failure approach was used where all participants with missing data were considered to have failed to reach the endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF (Blinded Randomized Phase) | Percentage of Participants With Normalized ALT at Week 48, Based on the AASLD Normal Range | 51.7 percentage of participants |
| Placebo (Blinded Randomized Phase) | Percentage of Participants With Normalized ALT at Week 48, Based on the AASLD Normal Range | 17.9 percentage of participants |
p-value: 0.002Cochran-Mantel-Haenszel
Secondary
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
Population: Participants in the Full Analysis Set with abnormal ALT values at baseline were analyzed. The missing equals failure approach was used where all participants with missing data were considered to have failed to reach the endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF (Blinded Randomized Phase) | Percentage of Participants With Normalized ALT at Week 48, Based on the Central Lab Normal Range | 65.5 percentage of participants |
| Placebo (Blinded Randomized Phase) | Percentage of Participants With Normalized ALT at Week 48, Based on the Central Lab Normal Range | 14.8 percentage of participants |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Percent Change From Baseline in BMD of Spine at Week 192
Time frame: Baseline; Week 192
Population: Participants in the Spine DXA Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TDF (Blinded Randomized Phase) | Percent Change From Baseline in BMD of Spine at Week 192 | 19.168 Percent change in spine BMD | Standard Deviation 12.2805 |
| Placebo (Blinded Randomized Phase) | Percent Change From Baseline in BMD of Spine at Week 192 | 26.085 Percent change in spine BMD | Standard Deviation 14.2586 |
Secondary
Percent Change From Baseline in BMD of Spine at Week 48
Time frame: Baseline; Week 48
Population: Participants in the Spine DXA Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TDF (Blinded Randomized Phase) | Percent Change From Baseline in BMD of Spine at Week 48 | 3.798 Percent change in spine BMD | Standard Deviation 5.9118 |
| Placebo (Blinded Randomized Phase) | Percent Change From Baseline in BMD of Spine at Week 48 | 7.557 Percent change in spine BMD | Standard Deviation 4.979 |
p-value: 0.007ANOVA