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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: HIV Infection; Hepatitis B
• Intervention / Treatment: Biological: HEPLISAV-B; Biological: ENGERIX-B

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 640
• Phase: Phase 3

Contacts and Locations

Study Locations

• Botswana
  • South-East District
    • Gaborone, South-East District, Botswana
      • Gaborone CRS
• Brazil
  • Rio De Janeiro, Brazil, 21040-360
    • Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 91350
      • Hospital Nossa Senhora da Conceicao CRS
• Haiti
  • Port-au-Prince, Haiti, HT-6110
    • Les Centres GHESKIO Clinical Research Site (GHESKIO-INLR) CRS
  • Port-au-Prince, Haiti, HT-6110
    • GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRS
• Kenya
  • Rift Valley
    • Kericho, Rift Valley, Kenya, 20200
      • Kenya Medical Research Institute/Walter Reed Project Clinical Research Center (KEMRI/WRP) CRS
• Malawi
  • Blantyre, Malawi
    • Blantyre CRS
• Philippines
  • Cavite, Philippines, 4114
    • De La Salle Health Science Institute Angelo King Medical Research Center (DLSHSI-AKMRC)
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2092
      • Wits Helen Joseph Hospital CRS (Wits HJH CRS), Perth Road, Westdene
  • Kwa Zulu Natal
    • Durban, Kwa Zulu Natal, South Africa, 4052
      • Durban International Clinical Research Site CRS
  • Soweto
    • Johannesburg, Soweto, South Africa, 1862
      • Soweto ACTG CRS
• Thailand
  • Bangkok, Thailand, 10330
    • Thai Red Cross AIDS Research Centre (TRC-ARC) CRS
  • Chiang Mai, Thailand, 50200
    • Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS
• Uganda
  • Kampala, Uganda, 10005
    • Joint Clinical Research Centre (JCRC)/Kampala Clinical Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35222
      • Alabama CRS
  • California
    • Los Angeles, California, United States, 90035-4709
      • UCLA CARE Center CRS
    • San Diego, California, United States, 92103
      • UCSD Antiviral Research Center
    • San Francisco, California, United States, 94110
      • Ucsf Hiv/Aids Crs
    • Torrance, California, United States, 90502
      • Harbor-UCLA CRS
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital CRS
  • District of Columbia
    • Washington, District of Columbia, United States, 20005
      • Whitman-Walker Health CRS
  • Georgia
    • Atlanta, Georgia, United States, 30308-2012
      • The Ponce de Leon Center CRS
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University CRS
    • Chicago, Illinois, United States, 60611
      • Northwestern University CRS
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University CRS
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital CRS (MGH CRS)
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital Therapeutics Clinical Research Site (BWH TCRS) CRS
  • Missouri
    • Saint Louis, Missouri, United States, 63110-1010
      • Washington University Therapeutics (WT) CRS
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • New Jersey Medical School Clinical Research Center CRS
  • New York
    • New York, New York, United States, 10032
      • Columbia P&S CRS
    • New York, New York, United States, 10065
      • Weill Cornell Uptown CRS
    • New York, New York, United States, 10010
      • Weill Cornell Chelsea CRS
    • Rochester, New York, United States, 14642
      • University of Rochester Adult HIV Therapeutic Strategies Network CRS
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Chapel Hill CRS
    • Greensboro, North Carolina, United States, 27401
      • Greensboro CRS
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Cincinnati Clinical Research Site
    • Cleveland, Ohio, United States, 44106
      • Case Clinical Research Site
    • Columbus, Ohio, United States, 43210
      • Ohio State University CRS
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Therapeutics CRS
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh CRS
  • Tennessee
    • Nashville, Tennessee, United States, 47183
      • Venderbilt Therapeutics (VT) CRS
  • Texas
    • Dallas, Texas, United States, 75208
      • Trinity Health and Wellness Center CRS
    • Houston, Texas, United States, 77009
      • Houston AIDS Research Team CRS
  • Washington
    • Seattle, Washington, United States, 98104-9929
      • University of Washington AIDS CRS
• Vietnam
  • Hanoi
    • Đống Đa, Hanoi, Vietnam, 10000
      • Hanoi Medical University CRS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A, Arm 1: HEPLISAV-B (two injections); Participants will receive 0.5 mL of HEPLISAV-B by intramuscular (IM) injection at Weeks 0 and 4.	Biological: HEPLISAV-B; Administered by IM injection
Experimental: Group A, Arm 2: HEPLISAV-B (three injections); Participants will receive 0.5 mL of HEPLISAV-B by IM injection at Weeks 0, 4, and 24.	Biological: HEPLISAV-B; Administered by IM injection
Experimental: Group A, Arm 3: ENGERIX-B (three injections); Participants will receive 1 mL of ENGERIX-B by IM injection at Weeks 0, 4, and 24.	Biological: ENGERIX-B; Administered by IM injection
Experimental: Group B: HEPLISAV-B (three injections); Participants will receive 0.5 mL of HEPLISAV-B by IM injection at Weeks 0, 4, and 24.	Biological: HEPLISAV-B; Administered by IM injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroprotection response defined as hepatitis B virus surface antibody (HBsAb) ≥10 mIU/mL		Week 12 in Group A, Arm 1, Week 28 in Group A, Arms 2 and 3 and in Group B
Occurrence of Adverse events (AEs)	DAIDS AE Grading Table (Version 2.1) will be used.	From vaccination initiation to study discontinuation (Week 72 or premature discontinuation)

Secondary Outcome Measures

Outcome Measure	Time Frame
Seroprotection response defined as HBsAb ≥10 mIU/mL	Weeks 4, 8, 12, 24, 28, 32, 48, 52 and 72
HBsAb titer	Weeks 4, 8, 12, 24, 28, 32, 48, 52 and 72
Occurrence of Grade ≥2 AEs within 4 weeks after each injection	From vaccination initiation to Week 28

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Dynavax Technologies Corporation
• Investigators: Study Chair: Kenneth E. Sherman, MD, PhD, Cincinnati CRS; Study Chair: Kristen Marks, MD, Weill Cornell Chelsea CRS

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2020
• Primary Completion (Estimated): July 26, 2024
• Study Completion (Estimated): July 26, 2024

Study Registration Dates

• First Submitted: December 6, 2019
• First Submitted That Met QC Criteria: December 6, 2019
• First Posted (Actual): December 10, 2019

Study Record Updates

• Last Update Posted (Estimated): May 3, 2024
• Last Update Submitted That Met QC Criteria: May 1, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis; Hepatitis B
• Other Study ID Numbers: ACTG A5379; 38569 (Registry Identifier: DAIDS-ES Registry Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie results in the publication, after deidentification.
• IPD Sharing Time Frame: Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.

IPD Sharing Access Criteria

• With whom?

  • Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group.

• For what types of analyses?

  • To achieve aims in the proposal approved by the AIDS Clinical Trials Group.

• By what mechanism will data be made available?

  • Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at: https://submit.mis.s-3.net/ Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No