Clinical trial NCT04193189: B-Enhancement of HBV Vaccination in Persons Living With HIV (BEe-HIVe): Evaluation of HEPLISAV-B
Official title: B-Enhancement of HBV Vaccination in Persons Living With HIV (BEe-HIVe): Evaluation of HEPLISAV-B
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infection
Hepatitis B
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Dynavax Technologies Corporation
First posted: 2019-12-10
Enrollment: 640
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

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

Primary outcomes:
measure: Seroprotection response defined as hepatitis B virus surface antibody (HBsAb) ≥10 mIU/mL
timeFrame: Week 12 in Group A, Arm 1, Week 28 in Group A, Arms 2 and 3 and in Group B
measure: Occurrence of Adverse events (AEs)
timeFrame: From vaccination initiation to study discontinuation (Week 72 or premature discontinuation)
Secondary outcomes:
measure: Seroprotection response defined as HBsAb ≥10 mIU/mL
timeFrame: Weeks 4, 8, 12, 24, 28, 32, 48, 52 and 72
measure: HBsAb titer
timeFrame: Weeks 4, 8, 12, 24, 28, 32, 48, 52 and 72
measure: Occurrence of Grade ≥2 AEs within 4 weeks after each injection
timeFrame: From vaccination initiation to Week 28
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama CRS
state: Alabama
city: Los Angeles
country: United States
facility: UCLA CARE Center CRS
state: California
city: San Diego
country: United States
facility: UCSD Antiviral Research Center
state: California
city: San Francisco
country: United States
facility: Ucsf Hiv/Aids Crs
state: California
city: Torrance
country: United States
facility: Harbor-UCLA CRS
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital CRS
state: Colorado
city: Washington
country: United States
facility: Whitman-Walker Health CRS
state: District of Columbia
city: Atlanta
country: United States
facility: The Ponce de Leon Center CRS
state: Georgia
city: Chicago
country: United States
facility: Northwestern University CRS
state: Illinois
city: Chicago
country: United States
facility: Rush University CRS
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University CRS
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital CRS (MGH CRS)
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital Therapeutics Clinical Research Site (BWH TCRS) CRS
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University Therapeutics (WT) CRS
state: Missouri
city: Newark
country: United States
facility: New Jersey Medical School Clinical Research Center CRS
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Chelsea CRS
state: New York
city: New York
country: United States
facility: Columbia P&S CRS
state: New York
city: New York
country: United States
facility: Weill Cornell Uptown CRS
state: New York
city: Rochester
country: United States
facility: University of Rochester Adult HIV Therapeutic Strategies Network CRS
state: New York
city: Chapel Hill
country: United States
facility: Chapel Hill CRS
state: North Carolina
city: Greensboro
country: United States
facility: Greensboro CRS
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Clinical Research Site
state: Ohio
city: Cleveland
country: United States
facility: Case Clinical Research Site
state: Ohio
city: Columbus
country: United States
facility: Ohio State University CRS
state: Ohio
city: Philadelphia
country: United States
facility: Penn Therapeutics CRS
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh CRS
state: Pennsylvania
city: Nashville
country: United States
facility: Venderbilt Therapeutics (VT) CRS
state: Tennessee
city: Dallas
country: United States
facility: Trinity Health and Wellness Center CRS
state: Texas
city: Houston
country: United States
facility: Houston AIDS Research Team CRS
state: Texas
city: Seattle
country: United States
facility: University of Washington AIDS CRS
state: Washington
city: Gaborone
country: Botswana
facility: Gaborone CRS
state: South-East District
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceicao CRS
state: Rio Grande Do Sul
city: Rio De Janeiro
country: Brazil
facility: Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
city: Port-au-Prince
country: Haiti
facility: GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRS
city: Port-au-Prince
country: Haiti
facility: Les Centres GHESKIO Clinical Research Site (GHESKIO-INLR) CRS
city: Kericho
country: Kenya
facility: Kenya Medical Research Institute/Walter Reed Project Clinical Research Center (KEMRI/WRP) CRS
state: Rift Valley
city: Blantyre
country: Malawi
facility: Blantyre CRS
city: Cavite
country: Philippines
facility: De La Salle Health Science Institute Angelo King Medical Research Center (DLSHSI-AKMRC)
city: Johannesburg
country: South Africa
facility: Wits Helen Joseph Hospital CRS (Wits HJH CRS), Perth Road, Westdene
state: Gauteng
city: Durban
country: South Africa
facility: Durban International Clinical Research Site CRS
state: Kwa Zulu Natal
city: Johannesburg
country: South Africa
facility: Soweto ACTG CRS
state: Soweto
city: Bangkok
country: Thailand
facility: Thai Red Cross AIDS Research Centre (TRC-ARC) CRS
city: Chiang Mai
country: Thailand
facility: Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS
city: Kampala
country: Uganda
facility: Joint Clinical Research Centre (JCRC)/Kampala Clinical Research Site
city: Đống Đa
country: Vietnam
facility: Hanoi Medical University CRS
state: Hanoi
Study officials:
affiliation: Cincinnati CRS
name: Kenneth E. Sherman, MD, PhD
role: STUDY_CHAIR
affiliation: Weill Cornell Chelsea CRS
name: Kristen Marks, MD
role: STUDY_CHAIR
References: