Clinical trial NCT03797014: B/F/TAF Switch Study for HIV-HBV Coinfection
Official title: Efficacy, Safety, and Tolerability of Bictegravir/Emtricitabine/Tenofovir Alafenamide in Adults With HIV-HBV Coinfection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV-1-infection
Hepatitis B
Keywords: HIV-1
Hepatitis B
HIV-HBV coinfection
Bictegravir
B/F/TAF
Tenofovir alafenamide
Biktarvy
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
First posted: 2019-01-08
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: HIV-1 RNA at Week 24
timeFrame: Week 24
measure: HBV DNA at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: HIV-1 RNA at Week 48
timeFrame: Week 48
measure: HBV DNA at Week 48
timeFrame: Week 48
measure: CD4 Cell Count Change at Week 24
timeFrame: Baseline; Week 24
measure: CD4 Cell Count Change at Week 48
timeFrame: Baseline; Week 48
measure: ALT Normalization at Week 24
timeFrame: Week 24
measure: ALT Normalization at Week 48
timeFrame: Week 48
measure: HBeAg Loss at Week 48
timeFrame: Week 48
measure: HBsAg Loss at Week 48
timeFrame: Week 48
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Institute of Human Virology Clinical Research Unit
state: Maryland
city: Philadelphia
country: United States
facility: Newlands Health
state: Pennsylvania
Study officials:
affiliation: Institute of Human Virology, University of Maryland
name: Joel V Chua, MD
role: PRINCIPAL_INVESTIGATOR
References: