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

NCT ID: NCT04193189

Last Updated: 2025-07-20

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

638 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-12-14

Study Completion Date

2024-08-13

Brief Summary

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The purpose of this study was to evaluate 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 and individuals who are naïve to HBV vaccination.

Detailed Description

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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:

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 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.

Conditions

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HIV Infection Hepatitis B

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Group A, 2-CpG: HEPLISAV-B (two injections)

Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by intramuscular (IM) injection at Weeks 0 and 4.

Group Type EXPERIMENTAL

HEPLISAV-B

Intervention Type BIOLOGICAL

Administered by IM injection

Group A, 3-CpG: HEPLISAV-B (three injections)

Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by IM injection at Weeks 0, 4, and 24.

Group Type EXPERIMENTAL

HEPLISAV-B

Intervention Type BIOLOGICAL

Administered by IM injection

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

Participants were prescribed 1 mL of ENGERIX-B (conventional hepatitis B vaccine with an aluminum hydroxide adjuvant) by IM injection at Weeks 0, 4, and 24.

Group Type ACTIVE_COMPARATOR

ENGERIX-B

Intervention Type BIOLOGICAL

Administered by IM injection

Group B: HEPLISAV-B (three injections)

Participants were prescribed 0.5 mL of HEPLISAV-B (hepatitis B vaccine with a cytosine phosphoguanine adjuvant) by IM injection at Weeks 0, 4, and 24.

Group Type EXPERIMENTAL

HEPLISAV-B

Intervention Type BIOLOGICAL

Administered by IM injection

Interventions

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HEPLISAV-B

Administered by IM injection

Intervention Type BIOLOGICAL

ENGERIX-B

Administered by IM injection

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

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


* 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

* 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


* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Dynavax Technologies Corporation

INDUSTRY

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kenneth E. Sherman, MD, PhD

Role: STUDY_CHAIR

Cincinnati CRS

Kristen Marks, MD

Role: STUDY_CHAIR

Weill Cornell Chelsea CRS

Locations

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Alabama CRS

Birmingham, Alabama, United States

Site Status

UCLA CARE Center CRS

Los Angeles, California, United States

Site Status

UCSD Antiviral Research Center

San Diego, California, United States

Site Status

Ucsf Hiv/Aids Crs

San Francisco, California, United States

Site Status

Harbor-UCLA CRS

Torrance, California, United States

Site Status

University of Colorado Hospital CRS

Aurora, Colorado, United States

Site Status

Whitman-Walker Health CRS

Washington D.C., District of Columbia, United States

Site Status

The Ponce de Leon Center CRS

Atlanta, Georgia, United States

Site Status

Northwestern University CRS

Chicago, Illinois, United States

Site Status

Johns Hopkins University CRS

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital CRS (MGH CRS)

Boston, Massachusetts, United States

Site Status

Brigham and Women's Hospital Therapeutics Clinical Research Site (BWH TCRS) CRS

Boston, Massachusetts, United States

Site Status

Washington University Therapeutics (WT) CRS

St Louis, Missouri, United States

Site Status

New Jersey Medical School Clinical Research Center CRS

Newark, New Jersey, United States

Site Status

Weill Cornell Chelsea CRS

New York, New York, United States

Site Status

Columbia P&S CRS

New York, New York, United States

Site Status

Weill Cornell Uptown CRS

New York, New York, United States

Site Status

University of Rochester Adult HIV Therapeutic Strategies Network CRS

Rochester, New York, United States

Site Status

Chapel Hill CRS

Chapel Hill, North Carolina, United States

Site Status

Greensboro CRS

Greensboro, North Carolina, United States

Site Status

Cincinnati Clinical Research Site

Cincinnati, Ohio, United States

Site Status

Case Clinical Research Site

Cleveland, Ohio, United States

Site Status

Ohio State University CRS

Columbus, Ohio, United States

Site Status

Penn Therapeutics CRS

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh CRS

Pittsburgh, Pennsylvania, United States

Site Status

Vanderbilt Therapeutics (VT) CRS

Nashville, Tennessee, United States

Site Status

Houston AIDS Research Team CRS

Houston, Texas, United States

Site Status

University of Washington AIDS CRS

Seattle, Washington, United States

Site Status

Gaborone CRS

Gaborone, South-East District, Botswana

Site Status

Hospital Nossa Senhora da Conceicao CRS

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS

Rio de Janeiro, , Brazil

Site Status

Kenya Medical Research Institute/Walter Reed Project Clinical Research Center (KEMRI/WRP) CRS

Kericho, Rift Valley, Kenya

Site Status

Blantyre CRS

Blantyre, , Malawi

Site Status

De La Salle Health Science Institute Angelo King Medical Research Center

Silang, , Philippines

Site Status

Wits Helen Joseph Hospital CRS (Wits HJH CRS), Perth Road, Westdene

Johannesburg, Gauteng, South Africa

Site Status

Durban International Clinical Research Site CRS

Durban, KwaZulu-Natal, South Africa

Site Status

Soweto ACTG CRS

Johannesburg, Soweto, South Africa

Site Status

Thai Red Cross AIDS Research Centre (TRC-ARC) CRS

Bangkok, , Thailand

Site Status

Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS

Chiang Mai, , Thailand

Site Status

Joint Clinical Research Centre (JCRC)/Kampala Clinical Research Site

Kampala, , Uganda

Site Status

Hanoi Medical University CRS

Đống Đa, Hanoi, Vietnam

Site Status

Countries

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United States Botswana Brazil Kenya Malawi Philippines South Africa Thailand Uganda Vietnam

References

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Marks KM, Kang M, Umbleja T, Avihingsanon A, Sugandhavesa P, Cox AL, Vigil K, Perazzo H, Price JC, Katsidzira L, Vernon C, Alston-Smith B, Sherman KE; ACTG 5379 Study Team. Immunogenicity and Safety of Hepatitis B Virus (HBV) Vaccine With a Toll-Like Receptor 9 Agonist Adjuvant in HBV Vaccine-Naive People With Human Immunodeficiency Virus. Clin Infect Dis. 2023 Aug 14;77(3):414-418. doi: 10.1093/cid/ciad201.

Reference Type RESULT
PMID: 37017075 (View on PubMed)

Marks KM, Kang M, Umbleja T, Cox A, Vigil KJ, Ta NT, Omoz-Oarhe A, Perazzo H, Kosgei J, Hatlen T, Price J, Katsidzira L, Supparatpinyo K, Knowles K, Alston-Smith BL, Rathod P, Sherman KE; ACTG 5379 (BEe-HIVe) Study Team. HepB-CpG vs HepB-Alum Vaccine in People With HIV and Prior Vaccine Nonresponse: The BEe-HIVe Randomized Clinical Trial. JAMA. 2025 Jan 28;333(4):295-306. doi: 10.1001/jama.2024.24490.

Reference Type RESULT
PMID: 39616603 (View on PubMed)

Kang M, Marks KM, Cox AL, Sherman KE. An efficient vaccine clinical trial: ACTG A5379 hepatitis B vaccine trial in persons with HIV. Vaccine. 2025 May 10;55:127028. doi: 10.1016/j.vaccine.2025.127028. Epub 2025 Mar 26.

Reference Type RESULT
PMID: 40147293 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Informed Consent Form: V3.0

View Document

Document Type: Study Protocol: Clarification Memo V3.0

View Document

Document Type: Study Protocol: Letter of Amendment V2.0

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://rsc.niaid.nih.gov/sites/default/files/daids-ae-grading-table-v2-nov2014.pdf

Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017

https://rsc.niaid.nih.gov/clinical-research-sites/manual-expedited-reporting-adverse-events-daids

Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010

Other Identifiers

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38569

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG A5379

Identifier Type: -

Identifier Source: org_study_id

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