Hepatitis B, HIV-1-infection
Conditions
Keywords
HIV-1, Hepatitis B, HIV-HBV coinfection, Bictegravir, B/F/TAF, Tenofovir alafenamide, Biktarvy
Brief summary
The primary objective of this study is to evaluate the efficacy and safety of fixed dose combination (FDC) bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in adults coinfected with both HIV-1 and hepatitis B. As this is a switch study, all eligible subjects enrolled will be switched from their current antiretroviral regimen to B/F/TAF will be followed on treatment for 48 weeks.
Interventions
DRUGB/F/TAF
Fixed dose combination B/F/TAF (50 mg/ 200 mg/ 25 mg/ tablet) administered orally once daily without regards to food.
Sponsors
Gilead Sciences
University of Maryland, Baltimore
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open label study
Intervention model description
This is an open-label phase 4 switch study to evaluate the efficacy, safety, and tolerability of FDC B/F/TAF in adults with HIV-1 and HBV coinfection.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age 18 years or older at enrollment. 2. Documented HIV-1 infection and currently on a stable regimen for at least 3 months if on an INSTI-based regimen (6 months if on a non-INSTI-based regimen) preceding the screening visit with documented plasma HIV-1 RNA ≤ 50 copies/mL for at least 3 months preceding the screening visit. 3. No known history of resistance to tenofovir alafenamide (TAF), emtricitabine (FTC), or Bictegravir (BIC). 4. Documented chronic hepatitis B infection, based on any of the following: a. Positive HBsAg result or nucleic acid test for HBV DNA (including qualitative, quantitative, and genotype testing) or positive HBeAg on two occasions at least 6 months apart (any combination of these tests performed 6 months apart is acceptable); or b. Negative immunoglobulin M (IgM) antibodies to HBV core antigen (anti-HBc IgM) AND a positive results on one of the following tests: HBsAg, HBeAg, or nucleic acid test for HBV DNA (including qualitative, quantitative, and genotype testing) prior to or at screening. 5. No current or prior regimen containing three active anti-HBV agents (i.e. cannot be on tenofovir alafenamide (TDF)/emtricitabine (FTC)/entecavir or TDF/lamivudine (3TC)/entecavir). 6. Must have a primary care provider(s) for medical management. 7. Females of childbearing potential must agree to utilize protocol recommended highly effective contraceptive methods or be non-heterosexually active or practice sexual abstinence from screening and throughout the duration of the study. Female subjects who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least 3 months prior to study drug dosing. 8. Male subjects must be willing to abstain from heterosexual intercourse or use a condom throughout the study period. 9. Stated willingness to comply with all study procedures and availability for the duration of the study. 10. Written informed consent must be obtained before any study procedure is performed.
Exclusion criteria
1. Females who are pregnant or breastfeeding. 2. Any known allergies to any of the components of B/F/TAF. 3. Treatment with another investigational drug within three months of enrollment. 4. Abnormal hematological and biochemical parameters at screening, including: 1. Absolute neutrophil count (ANC) \< 750 cells/mm3. 2. Platelets \< 50,000/mm3. 3. Hemoglobin \< 8.5 g/dL. 4. AST or ALT of \> 5 times upper limit of normal (ULN). 5. Estimated GFR \< 30 mL/min/1.73 m2. 6. Total bilirubin \> 1.5 times ULN. 5. Previous or current history of malignancy, other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma. Note: Those with a history of malignancy who are in remission for two or more years may be included in the study. 6. An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening. 7. Subjects experiencing decompensated cirrhosis (e.g. ascites, encephalopathy, or variceal bleeding). 8. Acute hepatitis in the 30 days prior to study entry. 9. Active tuberculosis infection. 10. Subjects receiving ongoing therapy with any medications contraindicated for co-administration with B/F/TAF FDC, including but not limited to the following medications: dofetilide, phenobarbital, phenytoin, carbamazepine, oxcarbamazepine, rifampin, rifapentine, cisapride, St. John's Wort, and Echinaceae. 11. Current alcohol or substance use that in the opinion of the investigator may interfere with subject study compliance. 12. Any other clinical conditions that in the opinion of the investigator would make the subject unsuitable for the study or unable to comply with the dosing requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HBV DNA at Week 24 | Week 24 | Proportion of participants with plasma HBV DNA \<29 IU/mL at Week 24 as defined by Missing=Failure Approach |
| HIV-1 RNA at Week 24 | Week 24 | Proportion of participants with HIV-1 RNA \<50 copies/mL at Week 24 by US FDA Snapshot Algorithm |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CD4 Cell Count Change at Week 24 | Baseline; Week 24 | Change from baseline in CD4 cell count at Week 24 |
| CD4 Cell Count Change at Week 48 | Baseline; Week 48 | Change from baseline in CD4 cell count at Week 48 |
| ALT Normalization at Week 24 | Week 24 | Proportion of participants with normal ALT at Week 24 |
| HIV-1 RNA at Week 48 | Week 48 | Proportion of participants with HIV-1 RNA \<50 copies/mL at Week 48 by US FDA Snapshot Algorithm |
| HBeAg Loss at Week 48 | Week 48 | Proportion of participants with hepatitis B envelop antigen (HBeAg) loss at Week 48 visit. |
| HBsAg Loss at Week 48 | Week 48 | Proportion of participants with hepatitis B surface antigen (HBsAg) loss at Week 48 visit. |
| ALT Normalization at Week 48 | Week 48 | Proportion of participants with normal ALT at Week 48 |
| HBV DNA at Week 48 | Week 48 | Proportion of participants with plasma HBV DNA \<29 IU/mL at Week 48 as defined by Missing=Failure Approach |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| B/F/TAF Treatment group (1-arm study)
B/F/TAF: Fixed dose combination B/F/TAF (50 mg/ 200 mg/ 25 mg/ tablet) administered orally once daily without regards to food. | 28 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | B/F/TAF |
|---|---|
| Abnormal ALT | 4 Participants |
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants |
| Age, Continuous | 50.1 years |
| Anti-HBe antibody positive | 10 Participants |
| CD4 count <200 cells/microliter | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| HBeAg positive | 12 Participants |
| HBV DNA PCR <29 IU/mL | 22 Participants |
| Hepatitis D antibody positive | 5 Participants |
| HIV RNA PCR <50 copies/mL | 20 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 25 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 | 3 Participants |
| Region of Enrollment United States | 28 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 28 |
| other Total, other adverse events | 16 / 28 |
| serious Total, serious adverse events | 0 / 28 |
Outcome results
Primary
HBV DNA at Week 24
Proportion of participants with plasma HBV DNA \<29 IU/mL at Week 24 as defined by Missing=Failure Approach
Time frame: Week 24
Population: Intention-to-Treat Population: All enrolled subjects who received at least one study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| B/F/TAF | HBV DNA at Week 24 | 24 Participants |
Primary
HIV-1 RNA at Week 24
Proportion of participants with HIV-1 RNA \<50 copies/mL at Week 24 by US FDA Snapshot Algorithm
Time frame: Week 24
Population: Intention-to-Treat (ITT) population: Enrolled subjects who received at least one study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| B/F/TAF | HIV-1 RNA at Week 24 | 25 Participants |
Secondary
ALT Normalization at Week 24
Proportion of participants with normal ALT at Week 24
Time frame: Week 24
Population: Enrolled subjects with abnormal ALT at baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| B/F/TAF | ALT Normalization at Week 24 | 4 Participants |
Secondary
ALT Normalization at Week 48
Proportion of participants with normal ALT at Week 48
Time frame: Week 48
Population: All enrolled subjects with abnormal baseline LFTs
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| B/F/TAF | ALT Normalization at Week 48 | 4 Participants |
Secondary
CD4 Cell Count Change at Week 24
Change from baseline in CD4 cell count at Week 24
Time frame: Baseline; Week 24
Population: All enrolled subjects with CD4 count values at baseline and at week 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| B/F/TAF | CD4 Cell Count Change at Week 24 | 32.8 cells/microliter | Standard Deviation 169.1 |
Secondary
CD4 Cell Count Change at Week 48
Change from baseline in CD4 cell count at Week 48
Time frame: Baseline; Week 48
Population: All enrolled subjects with CD4 count results available at baseline and week 48.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| B/F/TAF | CD4 Cell Count Change at Week 48 | 76.6 cells/microliter | Standard Deviation 184.2 |
Secondary
HBeAg Loss at Week 48
Proportion of participants with hepatitis B envelop antigen (HBeAg) loss at Week 48 visit.
Time frame: Week 48
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| B/F/TAF | HBeAg Loss at Week 48 | 0 Participants |
Secondary
HBsAg Loss at Week 48
Proportion of participants with hepatitis B surface antigen (HBsAg) loss at Week 48 visit.
Time frame: Week 48
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| B/F/TAF | HBsAg Loss at Week 48 | 0 Participants |
Secondary
HBV DNA at Week 48
Proportion of participants with plasma HBV DNA \<29 IU/mL at Week 48 as defined by Missing=Failure Approach
Time frame: Week 48
Population: Intention-to-Treat Population: All enrolled subjects who received at least one study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| B/F/TAF | HBV DNA at Week 48 | 22 Participants |
Secondary
HIV-1 RNA at Week 48
Proportion of participants with HIV-1 RNA \<50 copies/mL at Week 48 by US FDA Snapshot Algorithm
Time frame: Week 48
Population: Intention-to-Treat Population: All enrolled subjects who received at least one study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| B/F/TAF | HIV-1 RNA at Week 48 | 22 Participants |