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

This phase III/IV study evaluated the response to and safety of the HBV vaccine HEPLISAV-B in two study populations of people living with HIV: prior HBV vaccine recipients who are deemed non-responders (Group A) and individuals who are naïve to HBV vaccination (Group B). The analyses were conducted as separate evaluations of the two study populations for all primary and secondary objectives.

Group A (HBV vaccine non-responders)

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

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

Participants were 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):

2-CpG: Two doses of HEPLISAV-B at weeks 0 and 4.

3-CpG: Three doses of HEPLISAV-B at weeks 0, 4, and 24.

3-alum: Three doses of ENGERIX-B at weeks 0, 4, and 24.

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

Group B (Naïve to HBV vaccination)

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

In both groups, participants were scheduled to attend several study visits through Week 72. All participants were to remain on their antiretroviral therapy (ART), not provided by the study, throughout the study. Visits included physical examinations and blood collection. For 7 days after each vaccination, participants were asked to record temperature and any reactions they experienced.

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