B-Enhancement of HBV Vaccination in Persons Living With HIV (BEe-HIVe): Evaluation of HEPLISAV-B

The purpose of this study is to evaluate response to and safety of the HBV vaccine HEPLISAV-B in two study populations living with HIV: prior HBV vaccine recipients who are deemed non-responders and individuals who are naïve to HBV vaccination.

This phase III/IV study will evaluate the response to and safety of the HBV vaccine HEPLISAV-B in two study populations living with HIV: prior HBV vaccine recipients who are deemed non-responders (Group A) and individuals who are naïve to HBV vaccination (Group B).

Group A (HBV vaccine non-responders)

The study is designed as an open-label three-arm study to evaluate whether:

1. HEPLISAV-B vaccination given as a two-dose series achieves non-inferior seroprotection response (SPR) compared to standard dose ENGERIX-B.
2. HEPLISAV-B vaccination given as a three-dose series achieves superior SPR proportion compared to standard dose ENGERIX-B.

Participants are randomized in 1:1:1 ratio to the following study arms, stratified by sex at birth (male vs. female) and diabetes diagnosis status (yes vs. no):

* Arm 1: Two doses of HEPLISAV-B at weeks 0 and 4.
* Arm 2: Three doses of HEPLISAV-B at weeks 0, 4, and 24.
* Arm 3: Three doses of ENGERIX-B at weeks 0, 4, and 24.

The target sample size in Group A is 561 participants, 187 participants in each arm.

Group B (Naïve to HBV vaccination)

Group B study is a single arm evaluation of vaccine response and safety of three doses of HEPLISAV-B. The target sample size is 73 participants.

All participants will remain on their non-study-provided antiretroviral therapy (ART) throughout the study. Participants in both groups will attend several study visits through Week 72. Visits may include physical examinations and blood collection. For 7 days after each vaccination, participants will record temperature and any reactions they have to the vaccine.

Eligibility Criteria:
Inclusion Criteria, Groups A and B

* HIV-1 infection
* On current HIV-1 antiretroviral therapy (ART)
* CD4+ T-cell count ≥100 cells/mm\^3
* HIV-1 RNA \<1000 copies/mL

Inclusion Criteria, Group A only

* Serum Hepatitis B antibody \<10 mlU/mL, non-reactive (negative), or indeterminate
* Documentation of HBV vaccination \>168 days prior to study entry

Inclusion Criterion, Group B only

* Serum Hepatitis B antibody non-reactive (negative) within 45 days prior to study entry

Exclusion Criteria, Groups A and B

* Infection or prior exposure to HBV
* Serum HBsAb level ≥10 mlU/mL or positive at screening or any other time prior to screening
* Presence of any active or acute AIDS-defining opportunistic infections
* Solid organ transplantation
* History of ascites, encephalopathy, or variceal hemorrhage
* Diagnosis of chronic kidney disease (CKD) stage G4
* Cancer diagnosis within 5 years
* Currently receiving chemotherapy
* Chronic use and/or receipt of systemically administered immunosuppressive
* Known allergy/sensitivity or any hypersensitivity to any HBV vaccine or yeast
* Active, serious infection other than HIV-1
* Receipt of any inactivated virus vaccine within 14 days
* Receipt of any of the following within 45 days prior to study entry:

  * Live virus vaccine
  * Granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF)
  * Any other investigational medicinal agent
* Receipt of immunoglobulin or blood products within 90 days prior to study entry
* Receipt of an injection of DNA plasmids or oligonucleotides within 60 days prior to study entry

Exclusion Criteria, Group A only

* Hepatitis B virus vaccination ≤168 days prior to study entry
* Receipt of HEPLISAV-B vaccine at any time prior to study entry

Exclusion Criterion, Group B only

* Known HBV vaccination prior to study entry