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

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase: Active, not recruiting; Phase 3

Conditions: HIV Infection; Hepatitis B

Treatments: Biological: HEPLISAV-B; Biological: ENGERIX-B

Study type: Interventional

Funder types: Industry; NIH

Identifiers

NCT04193189

38569

ACTG A5379

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 640 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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640 participants in 4 patient groups

Group A, Arm 1: HEPLISAV-B (two injections)

Experimental group

Description:

Participants will receive 0.5 mL of HEPLISAV-B by intramuscular (IM) injection at Weeks 0 and 4.

Treatment:

Biological: HEPLISAV-B

Group A, Arm 2: HEPLISAV-B (three injections)

Experimental group

Description:

Participants will receive 0.5 mL of HEPLISAV-B by IM injection at Weeks 0, 4, and 24.

Treatment:

Biological: HEPLISAV-B

Group A, Arm 3: ENGERIX-B (three injections)

Experimental group

Description:

Participants will receive 1 mL of ENGERIX-B by IM injection at Weeks 0, 4, and 24.

Treatment:

Biological: ENGERIX-B

Group B: HEPLISAV-B (three injections)

Experimental group

Description:

Participants will receive 0.5 mL of HEPLISAV-B by IM injection at Weeks 0, 4, and 24.

Treatment:

Biological: HEPLISAV-B