HIV InfectionsHBR2NCT05791851
Heplisav-B Revaccination for Hepatitis B Vaccine Nonresponders
An observational study of HIV Infections and Hepatitis B, run by University of Maryland, Baltimore at 2 sites in United States.
Trial summary
The goal of this natural history study is to examine the immune responses to the Heplisav-B vaccine in Veterans living with HIV who were non-responders to prior HBV vaccination. A comparison group of HBV vaccine nonresponders without HIV infection will be enrolled to characterize the HIV-associated immune alterations… Read more about this study
- Who is it for?
- Ages 18 to 109 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV Infections, Hepatitis B, Vaccine Response Impaired
- How many people
- 31 participants
- Where
- 2 sitesUnited States
- Study dates
- 23 Oct 2019to 14 Jun 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 109 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: The target population includes patients (or healthcare providers) who have received prior Hepatitis B vaccines without achieving seroprotection (defined as a negative SAb qualitative titer or a SAb quantitative titer <10 mIU/mL collected at least 30 days after last vaccine dose). The primary enrollment group will include Veterans living with HIV, with a comparator group of HIV-negative individuals. An additional exploratory population of HBV vaccine nonresponders who were successfully treated for HCV infection may be included to provide an opportunity for evaluation of the immune responses in patients who have been cured of chronic viral infections.
Who may be able to join
- Age >18 by age of screening
- If HIV positive, either:
- Suppressed on a stable, ARV regimen for >4 weeks with CD4 count >100. HIV VL suppressed <50 copies/mL, although single isolated VL >50 not excluded.
- OR
- Untreated ≥ 8 weeks with CD4 count >100
- Prior HBV vaccine (other than Heplisav) with last dose >30 days prior to screening and anti-HBSAg ≤10 IU/mL measured >30days from last vaccine dose. (No exclusion for HBV CAb positive.)
Show all 9Show fewer
- Ability to provide informed consent and adhere to clinic visits (in the judgment of both the participant and the provider)
- No history of adverse reaction to HBV vaccines or components thereof
- If HCV Ab positive: undetectable HCV viral load and >12 weeks from completion of any HCV therapy.
Who cannot join
- History of allergic reaction to HBV vaccines or components (including yeast)
- HBsAb titer >10 IU/mL on screening evaluation
- Clinically significant illness (other than HIV) that may, in the opinion of the investigator, interfere with the subject treatment, or adherence to protocol. This may include but is not limited to a history of transplant, decompensated cirrhosis, or malignancy that may interfere with host immunity.
- Poor venous access interfering with blood sample collection
- Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent.
- No exclusion will be made for chronic renal disease or ESRD
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Baltimore Veterans Affairs Medical Center
Baltimore, Maryland, 21201
Institute of Human Virology
Baltimore, Maryland, 21201
About this study
The goal of this natural history study is to examine the immune responses to the Heplisav-B vaccine in Veterans living with HIV who were non-responders to prior HBV vaccination. A comparison group of HBV vaccine nonresponders without HIV infection will be enrolled to characterize the HIV-associated immune alterations that affect vaccine response. The investigators hypothesize that TLR9-mediated innate immune stimulation with Heplisav will elicit HBV seroprotection despite prior vaccination failures in persons living with HIV, compared to HIV uninfected individuals.
Participants eligible for Heplisav-B vaccination will be asked to provide blood samples at multiple timepoints before and after their vaccination.
Read the detailed description
HIV-positive individuals are at increased risk of morbidity and mortality from Hepatitis B co-infection, due to shared routes of transmission, increased likelihood of developing chronic infection (as opposed to spontaneous clearance), and increased immune dysregulation leading to accelerated disease progression, and so current guidelines recommend the routine vaccination of HIV-positive individuals against HBV. However, because achieved seroprotection rates (SPR) are historically lower than in HIV-negative individuals, post-vaccination serologic testing is recommended for this group and re-vaccination (with increased dose or additional doses) should be attempted for those who were non-responders to the initial vaccine. Heplisav-B is a HBV vaccine adjuvanted with a TLR9 agonist that has shown improved SPR among groups with reduced response rates to classic alum-adjuvanted vaccines, such as those with CKD, obesity, or diabetes. The investigators propose to evaluate immunological mechanisms of protection in Veterans who were non-responders to prior HBV vaccination now receiving Heplisav vaccinations. The investigators will enroll a comparison group of HIV-negative individuals to characterize the HIV-associated immune alterations that modulate vaccine response. The investigators hypothesize that TLR9-mediated innate immune stimulation with Heplisav will elicit HBV seroprotection despite prior vaccination failures in persons living with HIV, compared to HIV uninfected individuals. By assessing innate immune responses and B cell immunophenotypes at baseline, post-vaccination, and at long-term followup in Veterans with and without HIV the investigators will assess the mechanisms by which the immunostimulatory effects of TLR9 agonists may overcome the immune dysfunction in these patients.
- Conditions
- HIV Infections, Hepatitis B, Vaccine Response Impaired
- Keywords
- Heplisav-B, HIV, vaccine
- Medical subject headings
- HIV Infections, Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| HIV infected | Not described | |
| HIV uninfected | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in B cell functional responses
Characterize the change in B cell functional responses by ELISpot on day 30 compared to baseline
Measured: Day 30
Change in B cell functional responses
Characterize the change in B cell functional responses by ELISpot on day 60 compared to baseline
Measured: Day 60
Change in B cell functional responses
Characterize the change in B cell functional responses by ELISpot on day 365 compared to baseline
Measured: Day 365
Change in B cell phenotypic responses
Characterize the change in B cell phenotypic responses by flow cytometry on day 365 compared to baseline
Measured: Day 30
Change in B cell phenotypic responses
Characterize the change in B cell phenotypic responses by flow cytometry on day 365 compared to baseline
Measured: Day 60
Change in B cell phenotypic responses
Characterize the change in B cell phenotypic responses by flow cytometry on day 365 compared to baseline
Measured: Day 365
Cytokine profile
Change in cytokine profile on day 1 compared to baseline
Measured: Day 1
Secondary outcomes (6)
Hepatitis B surface antibody responses
Characterization of the hepatitis B surface antibody titers on day 30 compared to baseline
Measured: Day 30
Hepatitis B surface antibody responses
Characterization of the hepatitis B surface antibody titers on day 60 compared to baseline
Measured: Day 60
Hepatitis B surface antibody responses
Characterization of the hepatitis B surface antibody titers on day 365 compared to baseline
Measured: Day 365
Hepatitis B surface antibody response rates
Characterization of the hepatitis B surface antibody response rates on day 30 compared to baseline
Measured: Day 30
Hepatitis B surface antibody response rates
Characterization of the hepatitis B surface antibody response rates on day 60 compared to baseline
Measured: Day 60
Hepatitis B surface antibody response rates
Characterization of the hepatitis B surface antibody response rates on day 365 compared to baseline
Measured: Day 365
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2023
- Study start23 Oct 2019
- Primary completion14 Jun 2022
- Study completion14 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by University of Maryland, BaltimoreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Collaborators
- Baltimore VA Medical Center
- Responsible party
- Principal investigator, Meagan Deming, University of Maryland, Baltimore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05791851
- Sponsor's protocol ID
- HP-83378
- Acronym
- HBR2
- Status last verified
- Mar 2023
- First submitted
- 7 Mar 2023
- Last updated
- 30 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Heplisav-B Revaccination for Hepatitis B Vaccine Nonresponders
- ClinicalTrials.gov ID
- NCT05791851
- Acronym / sponsor ID
- HBR2 / HP-83378
- Conditions
- HIV Infections, Hepatitis B, Vaccine Response Impaired
- Keywords
- Heplisav-B, HIV, vaccine
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Collaborators
- Baltimore VA Medical Center
- Study start
- 23 Oct 2019 (actual)
- Primary completion
- 14 Jun 2022 (actual)
- Study completion
- 14 Jun 2022 (actual)
- First posted
- 30 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this natural history study is to examine the immune responses to the Heplisav-B vaccine in Veterans living with HIV who were non-responders to prior HBV vaccination. A comparison group of HBV vaccine nonresponders without HIV infection will be enrolled to characterize the HIV-associated immune alterations that affect vaccine response. The investigators hypothesize that TLR9-mediated innate immune stimulation with Heplisav will elicit HBV seroprotection despite prior vaccination failures in persons living with HIV, compared to HIV uninfected individuals.
Participants eligible for Heplisav-B vaccination will be asked to provide blood samples at multiple timepoints before and after their vaccination.
Detailed description
HIV-positive individuals are at increased risk of morbidity and mortality from Hepatitis B co-infection, due to shared routes of transmission, increased likelihood of developing chronic infection (as opposed to spontaneous clearance), and increased immune dysregulation leading to accelerated disease progression, and so current guidelines recommend the routine vaccination of HIV-positive individuals against HBV. However, because achieved seroprotection rates (SPR) are historically lower than in HIV-negative individuals, post-vaccination serologic testing is recommended for this group and re-vaccination (with increased dose or additional doses) should be attempted for those who were non-responders to the initial vaccine. Heplisav-B is a HBV vaccine adjuvanted with a TLR9 agonist that has shown improved SPR among groups with reduced response rates to classic alum-adjuvanted vaccines, such as those with CKD, obesity, or diabetes. The investigators propose to evaluate immunological mechanisms of protection in Veterans who were non-responders to prior HBV vaccination now receiving Heplisav vaccinations. The investigators will enroll a comparison group of HIV-negative individuals to characterize the HIV-associated immune alterations that modulate vaccine response. The investigators hypothesize that TLR9-mediated innate immune stimulation with Heplisav will elicit HBV seroprotection despite prior vaccination failures in persons living with HIV, compared to HIV uninfected individuals. By assessing innate immune responses and B cell immunophenotypes at baseline, post-vaccination, and at long-term followup in Veterans with and without HIV the investigators will assess the mechanisms by which the immunostimulatory effects of TLR9 agonists may overcome the immune dysfunction in these patients.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HIV infected | – | – |
| HIV uninfected | – | – |
Who may qualify
- Ages
- 18 to 109 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The target population includes patients (or healthcare providers) who have received prior Hepatitis B vaccines without achieving seroprotection (defined as a negative SAb qualitative titer or a SAb quantitative titer <10 mIU/mL collected at least 30 days after last vaccine dose). The primary enrollment group will include Veterans living with HIV, with a comparator group of HIV-negative individuals. An additional exploratory population of HBV vaccine nonresponders who were successfully treated for HCV infection may be included to provide an opportunity for evaluation of the immune responses in patients who have been cured of chronic viral infections.
Key inclusion criteria (9 listed)
- Age >18 by age of screening
- If HIV positive, either:
- OR
- Untreated ≥ 8 weeks with CD4 count >100
Key exclusion criteria (6 listed)
- History of allergic reaction to HBV vaccines or components (including yeast)
- HBsAb titer >10 IU/mL on screening evaluation
- Clinically significant illness (other than HIV) that may, in the opinion of the investigator, interfere with the subject treatment, or adherence to protocol. This may include but is not limited to a history of transplant, decompensated cirrhosis, or malignancy that may interfere with host immunity.
- Poor venous access interfering with blood sample collection
- Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change in B cell functional responses
Time frame: Day 30
Characterize the change in B cell functional responses by ELISpot on day 30 compared to baseline
Change in B cell functional responses
Time frame: Day 60
Characterize the change in B cell functional responses by ELISpot on day 60 compared to baseline
Change in B cell functional responses
Time frame: Day 365
Characterize the change in B cell functional responses by ELISpot on day 365 compared to baseline
Change in B cell phenotypic responses
Time frame: Day 30
Characterize the change in B cell phenotypic responses by flow cytometry on day 365 compared to baseline
Change in B cell phenotypic responses
Time frame: Day 60
Characterize the change in B cell phenotypic responses by flow cytometry on day 365 compared to baseline
Change in B cell phenotypic responses
Time frame: Day 365
Characterize the change in B cell phenotypic responses by flow cytometry on day 365 compared to baseline
Cytokine profile
Time frame: Day 1
Change in cytokine profile on day 1 compared to baseline
6 secondary outcomes
Hepatitis B surface antibody responses
Time frame: Day 30
Hepatitis B surface antibody responses
Time frame: Day 60
Hepatitis B surface antibody responses
Time frame: Day 365
Hepatitis B surface antibody response rates
Time frame: Day 30
Hepatitis B surface antibody response rates
Time frame: Day 60
Hepatitis B surface antibody response rates
Time frame: Day 365
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HIV Infections and Hepatitis B, run by University of Maryland, Baltimore at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in B cell functional responses (time frame: Day 30). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2023.