Chronic Hepatitis B
Conditions
Keywords
Hepatitis B, Hepatitis, Tenofovir disoproxil fumarate, Tenofovir DF, Asian-American
Brief summary
The purpose of this study is to evaluate the antiviral activity and safety of tenofovir disoproxil fumarate (TDF) in Asian-American adults (self-reported Asian descent, living in the United States) with chronic hepatitis B infection. All participants will receive active treatment with TDF for 48 weeks.
Detailed description
Efficacy of TDF will be evaluated for reductions in serum HBV DNA, changes in liver enzymes, and the generation of antibody to the virus. Safety will be assessed by evaluating adverse events, laboratory abnormalities, and the development of drug resistance mutations.
Interventions
DRUGTenofovir disoproxil fumarate
300-mg tablet (marketed formulation) taken orally once daily
Sponsors
Gilead Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Male or female * Asian-American, defined as a person of self-reported Asian ancestry who is residing in the United States (US) * 18 through 75 years of age, inclusive * Documented chronic HBV infection, defined as positive serum HBsAg =/\> 6 months * HBV DNA =/\> 10,000 copies/mL (PCR method) * ALT \> ULN and \</= 10 × ULN at screening or within the past 12 months prior to screening * Willing and able to provide written informed consent * Negative serum beta-human chorionic gonadotropin (HCG) pregnancy test (females of child-bearing potential) * Estimated glomerular filtration rate (creatinine clearance) =/\> 60 mL/min/1.73m\^2 by the Cockcroft-Gault equation * Adequate hematologic function (absolute neutrophil count =/\> 1,500/mm\^3; hemoglobin =/\> 10.0 g/dL) * No prior TDF therapy; participants may have taken \< 12 weeks of oral anti-HBV therapy, with the last dose =/\> 16 weeks prior to screening; participants may have received prior interferon, but must have discontinued interferon therapy =/\> 6 months prior to screening
Exclusion criteria
Participants who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) <400 Copies/mL (<69 IU/mL) | Week 48 | Blood samples were collected from study participants for measuring HBV DNA via polymerase chain reaction (PCR) method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With ALT Normalized (Baseline Values > ULN [34 U/L] and <= ULN at a Subsequent Visit) at Week 48 | Week 48 | A normal value at Week 48 after having elevated ALT at baseline; normal ALT is defined as being at or below the ULN for the central laboratory (34 U/L) |
| Number of Participants With Composite Endpoint of Hepatitis B Virus (HBV) DNA <400 Copies/mL (<69 IU/mL) and Normal ALT at Week 48 | Week 48 | Blood samples were collected for evaluating serum chemistry, including determination of ALT, and for measuring HBV DNA via PCR method. Composite endpoints proposed in the protocol included the percentage of participants with HBV DNA \< 400 copies/mL (\<69 IU/mL) and normal ALT (ALT \<= ULN \[34 U/L\]); and with HBV DNA \< 400 copies/mL, normal ALT, and HBeAg loss/seroconversion. Because so few participants lost hepatitis B e antigen (HBeAg) or developed antibody to hepatitis B e antigen (anti-HBe), only the composite endpoint of HBV DNA \< 400 copies/mL and normal ALT was analyzed. |
| Change From Baseline in FibroTest Value | Baseline and Week 48 | The FibroTest score is used to assess liver fibrosis and is calculated based on a formula including the participant's age and sex and 5 laboratory parameters: alpha 2 macroglobulin, haptoglobin, gamma-glutamyl transferase (GGT), bilirubin, and apolipoprotein A1. Scores can range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis. |
| Number of Participants With HBeAg/Hepatitis B Surface Antigen (HBsAg) Loss and Seroconversion | Week 48 | HBeAg/HBsAg loss is defined for an individual participant as HBeAg+/HBsAg+ at baseline and HBeAg-/HBsAg- at Week 48. HBeAg/HBsAg serocoversion is defined for an individual participant as HBeAg+/HBsAg+ at baseline and HBeAg-/HBsAg- and anti-HBe+/antibody to hepatitis B surface antigen+ (anti-HBs+) at Week 48. |
| Number of Participants With HBV DNA < 169 Copies/mL (<29 IU/mL) at Week 48 | Week 48 | Blood samples from study participants were collected for measuring HBV DNA via PCR method. |
| Number of Participants With Alanine Aminotransferase (ALT) Normal at Week 48 | Week 48 | Number of participants with normal ALT (at or below the upper limit of normal \[ULN\] for the central laboratory \[34 U/L\])at Week 48 |
| Number of Participants With Composite Endpoint of HBV DNA <400 Copies/mL (<69 IU/mL), Normal ALT, and Seroconversion to Anti-HBe | Week 48 | Composite endpoints proposed in the protocol included the percentage of participants with HBV DNA \< 400 copies/mL (\<69 IU/mL) and normal ALT (ALT \<= ULN); and with HBV DNA \< 400 copies/mL, normal ALT, and HBeAg loss/seroconversion. Because so few participants lost HBeAg or seroconverted to anti-HBe, only the composite endpoint of HBV DNA \< 400 copies/mL and normal ALT was analyzed. |
| Summary of Resistance Surveillance for Participants Without Virologic Breakthrough | Week 48 | Serum was collected for HBV resistance surveillance, and sequence analysis of the HBV polymerase was assessed through di-deoxy sequencing of baseline and postbaseline samples. |
| Summary of Resistance Surveillance for Participants With Virologic Breakthrough | Week 48 | Serum was collected for HBV resistance surveillance, and sequence analysis of the HBV polymerase was assessed through di-deoxy sequencing of baseline and postbaseline samples. |
| Summary of Resistance Surveillance for Participants Who Discontinued the Study Early | Week 48 | Serum was collected for HBV resistance surveillance, and sequence analysis of the HBV polymerase was assessed through di-deoxy sequencing of baseline and postbaseline samples. |
| Number of Participants With Composite Endpoint of HBV DNA <400 Copies/mL (<69 IU/mL), Normal ALT, and HBeAg Loss | Week 48 | Composite endpoints proposed in the protocol included the percentage of participants with HBV DNA \< 400 copies/mL (\<69 IU/mL) and normal ALT (ALT \<= ULN \[34 U/L\]); and with HBV DNA \< 400 copies/mL, normal ALT, and HBeAg loss/seroconversion. Because so few participants lost HBeAg or seroconverted to anti-HBe, only the composite endpoint of HBV DNA \< 400 copies/mL and normal ALT was analyzed. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| A: TDF Tenofovir disoproxil fumarate 300 mg by mouth daily | 90 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Pregnancy | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | A: TDF |
|---|---|
| Age Continuous | 36.8 years STANDARD_DEVIATION 10.49 |
| Alanine aminotransferase (ALT); upper limit of normal (ULN) = 34 U/L | 103.5 U/L STANDARD_DEVIATION 149.61 |
| ALT <=ULN | 23 Participants |
| ALT >ULN | 67 Participants |
| ALT (Multiples of ULN) | 2.628 multiples of ULN STANDARD_DEVIATION 3.5698 |
| Antibody to HBeAg (Anti-HBe) Positive | 38 Participants |
| Antibody to HBeAg (Anti-HBe) Unknown | 52 Participants |
| Ethnicity Asian-Cambodian | 1 Participants |
| Ethnicity Asian-Chinese | 58 Participants |
| Ethnicity Asian-Korean | 12 Participants |
| Ethnicity Asian-Vietnamese | 19 Participants |
| HBV genotype Genotype B | 43 Participants |
| HBV genotype Genotype C | 47 Participants |
| Hepatitis B e antigen (HBeAg) Negative | 37 Participants |
| Hepatitis B e antigen (HBeAg) Positive | 53 Participants |
| Hepatitis B virus (HBV) deoxyribonucleic acid (DNA) | 7.484 log10 copies/mL STANDARD_DEVIATION 1.7678 |
| Positive Hepatitis B surface antigen (HBsAg) | 90 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 90 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 | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment United States | 90 participants |
| Sex: Female, Male Female | 43 Participants |
| Sex: Female, Male Male | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 27 / 90 |
| serious Total, serious adverse events | 1 / 90 |
Outcome results
Primary
Number of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) <400 Copies/mL (<69 IU/mL)
Blood samples were collected from study participants for measuring HBV DNA via polymerase chain reaction (PCR) method.
Time frame: Week 48
Population: The enrolled-and-treated analysis set included participants who were enrolled into the study and received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Number of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) <400 Copies/mL (<69 IU/mL) | 74 Participants |
Secondary
Change From Baseline in FibroTest Value
The FibroTest score is used to assess liver fibrosis and is calculated based on a formula including the participant's age and sex and 5 laboratory parameters: alpha 2 macroglobulin, haptoglobin, gamma-glutamyl transferase (GGT), bilirubin, and apolipoprotein A1. Scores can range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis.
Time frame: Baseline and Week 48
Population: The enrolled-and-treated analysis set included participants who were enrolled into the study and received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tenofovir DF | Change From Baseline in FibroTest Value | -0.006 Scores on a scale | Standard Deviation 0.1024 |
Secondary
Number of Participants With Alanine Aminotransferase (ALT) Normal at Week 48
Number of participants with normal ALT (at or below the upper limit of normal \[ULN\] for the central laboratory \[34 U/L\])at Week 48
Time frame: Week 48
Population: The enrolled-and-treated analysis set included participants who were enrolled into the study and received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Number of Participants With Alanine Aminotransferase (ALT) Normal at Week 48 | 59 Participants |
Secondary
Number of Participants With ALT Normalized (Baseline Values > ULN [34 U/L] and <= ULN at a Subsequent Visit) at Week 48
A normal value at Week 48 after having elevated ALT at baseline; normal ALT is defined as being at or below the ULN for the central laboratory (34 U/L)
Time frame: Week 48
Population: The enrolled-and-treated analysis set included participants who were enrolled into the study, received at least one dose of study drug, and had baseline ALT \> ULN (34 U/L).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Number of Participants With ALT Normalized (Baseline Values > ULN [34 U/L] and <= ULN at a Subsequent Visit) at Week 48 | 40 participants |
Secondary
Number of Participants With Composite Endpoint of HBV DNA <400 Copies/mL (<69 IU/mL), Normal ALT, and HBeAg Loss
Composite endpoints proposed in the protocol included the percentage of participants with HBV DNA \< 400 copies/mL (\<69 IU/mL) and normal ALT (ALT \<= ULN \[34 U/L\]); and with HBV DNA \< 400 copies/mL, normal ALT, and HBeAg loss/seroconversion. Because so few participants lost HBeAg or seroconverted to anti-HBe, only the composite endpoint of HBV DNA \< 400 copies/mL and normal ALT was analyzed.
Time frame: Week 48
Secondary
Number of Participants With Composite Endpoint of HBV DNA <400 Copies/mL (<69 IU/mL), Normal ALT, and Seroconversion to Anti-HBe
Composite endpoints proposed in the protocol included the percentage of participants with HBV DNA \< 400 copies/mL (\<69 IU/mL) and normal ALT (ALT \<= ULN); and with HBV DNA \< 400 copies/mL, normal ALT, and HBeAg loss/seroconversion. Because so few participants lost HBeAg or seroconverted to anti-HBe, only the composite endpoint of HBV DNA \< 400 copies/mL and normal ALT was analyzed.
Time frame: Week 48
Secondary
Number of Participants With Composite Endpoint of Hepatitis B Virus (HBV) DNA <400 Copies/mL (<69 IU/mL) and Normal ALT at Week 48
Blood samples were collected for evaluating serum chemistry, including determination of ALT, and for measuring HBV DNA via PCR method. Composite endpoints proposed in the protocol included the percentage of participants with HBV DNA \< 400 copies/mL (\<69 IU/mL) and normal ALT (ALT \<= ULN \[34 U/L\]); and with HBV DNA \< 400 copies/mL, normal ALT, and HBeAg loss/seroconversion. Because so few participants lost hepatitis B e antigen (HBeAg) or developed antibody to hepatitis B e antigen (anti-HBe), only the composite endpoint of HBV DNA \< 400 copies/mL and normal ALT was analyzed.
Time frame: Week 48
Population: The enrolled-and-treated analysis set included participants who were enrolled into the study and received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Number of Participants With Composite Endpoint of Hepatitis B Virus (HBV) DNA <400 Copies/mL (<69 IU/mL) and Normal ALT at Week 48 | 55 Participants |
Secondary
Number of Participants With HBeAg/Hepatitis B Surface Antigen (HBsAg) Loss and Seroconversion
HBeAg/HBsAg loss is defined for an individual participant as HBeAg+/HBsAg+ at baseline and HBeAg-/HBsAg- at Week 48. HBeAg/HBsAg serocoversion is defined for an individual participant as HBeAg+/HBsAg+ at baseline and HBeAg-/HBsAg- and anti-HBe+/antibody to hepatitis B surface antigen+ (anti-HBs+) at Week 48.
Time frame: Week 48
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenofovir DF | Number of Participants With HBeAg/Hepatitis B Surface Antigen (HBsAg) Loss and Seroconversion | HBsAg+ at baseline | 90 Participants |
| Tenofovir DF | Number of Participants With HBeAg/Hepatitis B Surface Antigen (HBsAg) Loss and Seroconversion | HBsAg- at baseline | 0 Participants |
| Tenofovir DF | Number of Participants With HBeAg/Hepatitis B Surface Antigen (HBsAg) Loss and Seroconversion | HBsAg+ at Week 48 | 88 Participants |
| Tenofovir DF | Number of Participants With HBeAg/Hepatitis B Surface Antigen (HBsAg) Loss and Seroconversion | HBsAg data missing at Week 48 | 2 Participants |
| Tenofovir DF | Number of Participants With HBeAg/Hepatitis B Surface Antigen (HBsAg) Loss and Seroconversion | HBeAg+ at baseline | 53 Participants |
| Tenofovir DF | Number of Participants With HBeAg/Hepatitis B Surface Antigen (HBsAg) Loss and Seroconversion | HBeAg- at baseline | 37 Participants |
| Tenofovir DF | Number of Participants With HBeAg/Hepatitis B Surface Antigen (HBsAg) Loss and Seroconversion | HBeAg loss by Week 48 | 6 Participants |
| Tenofovir DF | Number of Participants With HBeAg/Hepatitis B Surface Antigen (HBsAg) Loss and Seroconversion | Anti-HBe+ seroconversion by Week 48 | 6 Participants |
Secondary
Number of Participants With HBV DNA < 169 Copies/mL (<29 IU/mL) at Week 48
Blood samples from study participants were collected for measuring HBV DNA via PCR method.
Time frame: Week 48
Population: The enrolled-and-treated analysis set included participants who were enrolled into the study and received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Number of Participants With HBV DNA < 169 Copies/mL (<29 IU/mL) at Week 48 | 73 Participants |
Secondary
Summary of Resistance Surveillance for Participants Who Discontinued the Study Early
Serum was collected for HBV resistance surveillance, and sequence analysis of the HBV polymerase was assessed through di-deoxy sequencing of baseline and postbaseline samples.
Time frame: Week 48
Population: 2 participants received \>= 1 dose of study drug, discontinued TDF treatment after Week 24 with HBV DNA \>= 400 copies/mL, and had serum sample for testing.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenofovir DF | Summary of Resistance Surveillance for Participants Who Discontinued the Study Early | No changes in HBV pol/RT | 1 Participants |
| Tenofovir DF | Summary of Resistance Surveillance for Participants Who Discontinued the Study Early | Changes at polymorphic sites | 0 Participants |
| Tenofovir DF | Summary of Resistance Surveillance for Participants Who Discontinued the Study Early | Changes at conserved sites | 0 Participants |
| Tenofovir DF | Summary of Resistance Surveillance for Participants Who Discontinued the Study Early | Unable to genotype | 1 Participants |
Secondary
Summary of Resistance Surveillance for Participants Without Virologic Breakthrough
Serum was collected for HBV resistance surveillance, and sequence analysis of the HBV polymerase was assessed through di-deoxy sequencing of baseline and postbaseline samples.
Time frame: Week 48
Population: 10 participants received \>= 1 dose of study drug, remained viremic (HBV DNA \>= 400 copies/mL) after 48 weeks of TDF treatment, had serum sample for testing, and did not have virologic breakthrough (defined as HBV DNA \>= 400 copies/mL \[confirmed\] after having HBV DNA levels \< 400 copies/mL and/or 1-log10 increase \[confirmed\] in HBV DNA above nadir).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenofovir DF | Summary of Resistance Surveillance for Participants Without Virologic Breakthrough | No changes in HBV pol/RT | 6 Participants |
| Tenofovir DF | Summary of Resistance Surveillance for Participants Without Virologic Breakthrough | Changes at polymorphic sites | 1 Participants |
| Tenofovir DF | Summary of Resistance Surveillance for Participants Without Virologic Breakthrough | Changes at conserved sites | 2 Participants |
| Tenofovir DF | Summary of Resistance Surveillance for Participants Without Virologic Breakthrough | Unable to genotype | 1 Participants |
Secondary
Summary of Resistance Surveillance for Participants With Virologic Breakthrough
Serum was collected for HBV resistance surveillance, and sequence analysis of the HBV polymerase was assessed through di-deoxy sequencing of baseline and postbaseline samples.
Time frame: Week 48
Population: 2 participants received \>= 1 dose of study drug, remained viremic (HBV DNA \>= 400 copies/mL) after 48 weeks of TDF treatment, had serum sample for testing, and had virologic breakthrough (defined as HBV DNA \>= 400 copies/mL \[confirmed\] after having HBV DNA levels \< 400 copies/mL and/or 1-log10 increase \[confirmed\] in HBV DNA above nadir).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenofovir DF | Summary of Resistance Surveillance for Participants With Virologic Breakthrough | Changes at conserved sites | 0 Participants |
| Tenofovir DF | Summary of Resistance Surveillance for Participants With Virologic Breakthrough | Unable to genotype | 0 Participants |
| Tenofovir DF | Summary of Resistance Surveillance for Participants With Virologic Breakthrough | No changes in HBV pol/RT | 2 Participants |
| Tenofovir DF | Summary of Resistance Surveillance for Participants With Virologic Breakthrough | Changes at polymorphic sites | 0 Participants |