Hepatitis B, Chronic
Conditions
Keywords
Tenofovir alafenamide (TAF)
Brief summary
Primary Objective: To describe rate of persistence and/or improvement of viral suppression with TAF as with previous anti-HBV (hepatitis B virus) treatment
Detailed description
Secondary Objective(s): 1. Describe persistence of ALT (alanine aminotransferase) normalization and/or improvement of ALT levels with TAF as with previous anti-HBV treatment 2. To describe trends in serum creatinine and calculated creatinine clearance as available by local labs. 3. To describe trends in bone mass from baseline to 24 months after switch. https://med.stanford.edu/nguyenlab/clinical-trials.html
Interventions
DRUGTenofovir Alafenamide
Tenofovir alafenamide (TAF) is a new formulation of tenofovir with higher intracellular active drug concentration allowing for dosing of only 25 mg once daily and thus can potentially lower the already low risk of renal toxicity and bone loss with tenofovir disoproxil fumarate (TDF).
Sponsors
Gilead Sciences
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female, age ≥18 years 2. Chronic hepatitis B diagnosis confirmed by positive HBsAg or HBV DNA or HBeAg or documented history of chronic hepatitis B in physician note 3. Currently maintained on antiviral therapy for at least 48 weeks with any Hepatitis B virus(HBV) DNA value at Screening/Baseline and planned to be switched to TAF by their physician 4. Routinely monitored for serum HBV DNA Polymerase chain reaction(PCR), liver chemistry including Aspartate aminotransferase (AST )/alanine transaminase(ALT)/total bilirubin, renal chemistry including Blood urea nitrogen(BUN)/Creatinine/Carbon dioxide (CO2) by their physicians every 3-6 months and a bone density scan at least every 2 years as per routine clinical care (one at baseline and one 2 years after switch). 5. Estimated creatinine clearance \> 15 ml/min (using the Cockcroft-Gault method) at Screening/Baseline Visit. (Note: multiply estimated rate by 0.85 for women). 6. Willing and able to provide informed consent 7. Able to comply with dosing instructions for study drug administration and able to complete the study schedule of assessments
Exclusion criteria
1. Pregnant women, women who are breastfeeding or who believe they may wish to become pregnant during the course of the study 2. Previous recipient of a liver transplant 3. Co-infection with human immunodeficiency virus (HIV) or hepatitis C (HCV) or hepatitis D (HDV) 4. Severe or uncontrolled comorbidities 5. Current or known hepatic decompensation (≤2 years) (e.g ascites, encephalopathy, or variceal hemorrhage) with a Child-Pugh score of B or C 6. Malignancy including liver cancer within 5 years except cancers curable by surgical resection (e.g. basal cell skin cancer and squamous cell cancer) 7. On any of the disallowed concomitant medications listed in the prior and concomitant medications list (pg. 11). Subjects on prohibited medications who are otherwise eligible will need a wash out period of at least 30 days prior to the Screening/Baseline visit. 8. Males and females of reproductive potential who are unwilling to use effective protocol-specified method(s) of contraception during the study. 9. Current substance or alcohol abuse judged by the investigator to potentially interfere with subject compliance. 10. Any other clinical conditions that, in the opinion of the Investigator, would make the subject unsuitable or unable to comply with any of the study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With HBV DNA <20 IU Per mL | Baseline, 6, 12, 18, 24 months | To describe rate of persistence and/or improvement of viral suppression with TAF as with previous anti-HBV treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Normal Alanine Aminotransferase (ALT). | Baseline, 6, 12, 18, 24 months | Alanine aminotransferase (ALT) normalization is defined if ALT was less than 35 U/L for men or 25 U/L for women |
| Calculated eGFR | Baseline, 6, 12, 18, 24 months | To describe trends in calculated eGFR as available by local labs. Estimated glomerular filtration rates (eGFR) were calculated using the Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI) equation (eGFR \[mL∕min∕1.73m2\] =141 × \[minimum Scr∕K, 1\]α × \[maximum Scr/K, 1\]1.209 × 0.993age × 1.018 \[if female\] × 1.159 \[if black\]) where Scr is serum creatinine in µmol/L, K is 61.9 for females and 79.6 for males, α is -0.329 for females and -0.411 for males |
| The Mean Bone Mass Density (T-score) Change | Baseline, month 24 | To describe trends in bone mass density from baseline to end of study. Bone Mass Density(BMD) was evaluated using T-score of Lumber-spine. The T-score is a comparison of the results to a average peak bone mass of healthy young adult. 0 indicates healthy young adult's mean with a SD of 1. Normal BMD was defined with T-score of -1.0 or above; osteopenia with T-score between -1.1 and -2.4, and osteoporosis with T-score of -2.5 or below (ref). Worsened BMD was defined by upstaging of BMD class from normal to osteopenia or worse or from osteopenia to osteoporosis. Improved BMD was defined by downstaging of BMD class from osteopenia to normal or osteoporosis to osteopenia or normal. |
Countries
Japan, South Korea, Taiwan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tenofovir Alafenamide for 24 Months Participants with chronic HBV infection receive TAF 25 mg for 24 months. | 270 |
| Total | 270 |
Baseline characteristics
| Characteristic | Tenofovir Alafenamide for 24 Months |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 83 Participants |
| Age, Categorical Between 18 and 65 years | 187 Participants |
| Age, Continuous | 58.1 years STANDARD_DEVIATION 10.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 269 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 269 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment Japan | 123 Participants |
| Region of Enrollment South Korea | 63 Participants |
| Region of Enrollment Taiwan | 53 Participants |
| Region of Enrollment United States | 31 Participants |
| Sex: Female, Male Female | 113 Participants |
| Sex: Female, Male Male | 157 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 270 |
| other Total, other adverse events | 4 / 270 |
| serious Total, serious adverse events | 15 / 270 |
Outcome results
Primary
Number of Participants With HBV DNA <20 IU Per mL
To describe rate of persistence and/or improvement of viral suppression with TAF as with previous anti-HBV treatment.
Time frame: Baseline, 6, 12, 18, 24 months
Population: Participants with data at each respective time point are included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tenofovir Alafenamide for 24 Months | Number of Participants With HBV DNA <20 IU Per mL | Baseline | 257 Participants |
| Tenofovir Alafenamide for 24 Months | Number of Participants With HBV DNA <20 IU Per mL | month 6 | 261 Participants |
| Tenofovir Alafenamide for 24 Months | Number of Participants With HBV DNA <20 IU Per mL | month 12 | 257 Participants |
| Tenofovir Alafenamide for 24 Months | Number of Participants With HBV DNA <20 IU Per mL | month 18 | 256 Participants |
| Tenofovir Alafenamide for 24 Months | Number of Participants With HBV DNA <20 IU Per mL | month 24 | 255 Participants |
Secondary
Calculated eGFR
To describe trends in calculated eGFR as available by local labs. Estimated glomerular filtration rates (eGFR) were calculated using the Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI) equation (eGFR \[mL∕min∕1.73m2\] =141 × \[minimum Scr∕K, 1\]α × \[maximum Scr/K, 1\]1.209 × 0.993age × 1.018 \[if female\] × 1.159 \[if black\]) where Scr is serum creatinine in µmol/L, K is 61.9 for females and 79.6 for males, α is -0.329 for females and -0.411 for males
Time frame: Baseline, 6, 12, 18, 24 months
Population: Participants with data at each respective time point are included in the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Tenofovir Alafenamide for 24 Months | Calculated eGFR | Baseline | 90.2 mL/min/1.73m^2 |
| Tenofovir Alafenamide for 24 Months | Calculated eGFR | month 6 | 90.8 mL/min/1.73m^2 |
| Tenofovir Alafenamide for 24 Months | Calculated eGFR | month 12 | 91.2 mL/min/1.73m^2 |
| Tenofovir Alafenamide for 24 Months | Calculated eGFR | month 18 | 91.8 mL/min/1.73m^2 |
| Tenofovir Alafenamide for 24 Months | Calculated eGFR | month 24 | 92.1 mL/min/1.73m^2 |
Secondary
Number of Participants With Normal Alanine Aminotransferase (ALT).
Alanine aminotransferase (ALT) normalization is defined if ALT was less than 35 U/L for men or 25 U/L for women
Time frame: Baseline, 6, 12, 18, 24 months
Population: Participants with data at each respective time point are included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tenofovir Alafenamide for 24 Months | Number of Participants With Normal Alanine Aminotransferase (ALT). | Baseline | 203 Participants |
| Tenofovir Alafenamide for 24 Months | Number of Participants With Normal Alanine Aminotransferase (ALT). | month 6 | 212 Participants |
| Tenofovir Alafenamide for 24 Months | Number of Participants With Normal Alanine Aminotransferase (ALT). | month 12 | 197 Participants |
| Tenofovir Alafenamide for 24 Months | Number of Participants With Normal Alanine Aminotransferase (ALT). | month 18 | 203 Participants |
| Tenofovir Alafenamide for 24 Months | Number of Participants With Normal Alanine Aminotransferase (ALT). | month 24 | 203 Participants |
Secondary
The Mean Bone Mass Density (T-score) Change
To describe trends in bone mass density from baseline to end of study. Bone Mass Density(BMD) was evaluated using T-score of Lumber-spine. The T-score is a comparison of the results to a average peak bone mass of healthy young adult. 0 indicates healthy young adult's mean with a SD of 1. Normal BMD was defined with T-score of -1.0 or above; osteopenia with T-score between -1.1 and -2.4, and osteoporosis with T-score of -2.5 or below (ref). Worsened BMD was defined by upstaging of BMD class from normal to osteopenia or worse or from osteopenia to osteoporosis. Improved BMD was defined by downstaging of BMD class from osteopenia to normal or osteoporosis to osteopenia or normal.
Time frame: Baseline, month 24
Population: Participants with data at each respective time point are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tenofovir Alafenamide for 24 Months | The Mean Bone Mass Density (T-score) Change | Baseline | -1.43 T-score | Standard Deviation 1.36 |
| Tenofovir Alafenamide for 24 Months | The Mean Bone Mass Density (T-score) Change | 24 month | -1.17 T-score | Standard Deviation 1.38 |