Use of Dynavax Heplisav B in Healthcare Workers Previously Vaccinated With 3-dose Vaccine Who Failed to Demonstrate Seroprotection

April 27, 2021 updated by: Ruth Carrico, University of Louisville

Use of Dynavax Heplisav B in Healthcare Workers Previously Vaccinated With Standard 3-dose Vaccine Who Failed to Demonstrate Seroprotection

Protection against Hepatitis B infection is a regulatory and safety cornerstone to infection prevention and control programs involving the healthcare workforce in the United States. Until 2018 when a new adjuvanted vaccine was released, immunization for this population has involved a three-dose series followed by an additional three-dose series for those demonstrating lack of seroprotection. If that lack continued following the second three-dose series, and verification of a negative Hepatitis B antigen status, that person has historically been deemed a non-responder to Hepatitis B vaccine and at potential risk for infection. This non-response status may be used to determine job responsibilities representing excessive risk for the healthcare worker resulting in potential career and practice limitations and decisions. With the release of the new adjuvanted vaccine, there is potential to determine the role that new vaccine may play in promoting an immune response among this non-responding subset of at-risk healthcare workers. The aims of this study include: 1) determining the effect of this adjuvanted vaccine in producing seropositivity in a population of healthcare personnel previously deemed as non-responders following administration of two rounds of the traditional 3-dose series of Hepatitis B vaccine and confirmation of negative Hepatitis B antigen; and 2) determining the personal and professional impact of the lack of immunity to Hepatitis B among healthcare personnel.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Background Protection against Hepatitis B infection is a regulatory and safety cornerstone to infection prevention and control programs involving the healthcare workforce in the United States. Until 2018 when a new adjuvanted vaccine was released, immunization for this population has involved a three-dose series followed by an additional three-dose series for those demonstrating lack of seroprotection. If that lack continued following the second three-dose series, and verification of a negative Hepatitis B antigen status, that person has historically been deemed a non-responder to Hepatitis B vaccine and at potential risk for infection. This non-response status may be used to determine job responsibilities representing excessive risk for the healthcare worker resulting in potential career and practice limitations and decisions. With the release of the new adjuvanted vaccine, there is potential to determine the role that new vaccine may play in promoting an immune response among this non-responding subset of at-risk healthcare workers.

Heplisav B is a standard of care vaccine that provides an alternative to a traditional 3-dose series by enabling use of a 2-dose series with doses one and two separated by one month. Work by Jackson and Janssen have indicated a greater than 90% seroprotection, perhaps closer to 100%, with the 2-dose series of this adjuvanted vaccine where hyporesponsiveness to 3-dose vaccines has been noted, principally in persons who smoke, are diabetic, obese, and male. This shorter administration schedule and reduced number of doses, combined with the seroconversion data make this vaccine ideal for situations where rapid induction of immunization occurs, such as those working in exposure-risk jobs such as healthcare.

The aims of this study include: 1) determining the effect of this adjuvanted vaccine in producing seropositivity in a population of healthcare personnel previously deemed as non-responders following administration of two rounds of the traditional 3-dose series of Hepatitis B vaccine and confirmation of negative Hepatitis B antigen; and 2) determining the personal and professional impact of the lack of immunity to Hepatitis B among healthcare personnel.

Use of Heplisav B will follow the FDA labeling and will not involve off-label use. Study personnel will work with the employee/occupational health and infection control departments to identify healthcare personnel working in a Louisville hospital, long term care facility, or clinic meeting the definition of a non-responder. Work will be done with University of Louisville Campus Health Services leadership to identify students, residents, fellows, or faculty who meet the definition of a non-responder. After gaining consent for participation in the study, titers will be drawn to document current Hepatitis B quantitative antibody and antigen levels. Enrolled participants (those with negative antibody and antigen) will be administered one dose of the adjuvanted vaccine followed by repeat antigen and antibody testing 30-60 days after receipt of that dose of vaccine. If results of the antibody and antigen are again negative, a second dose of the adjuvanted vaccine will be administered followed by repeat antibody and antigen testing 30-60 days after receipt of that dose of vaccine. For those healthcare personnel enrolled in the study, a questionnaire will be administered designed to understand the personal and professional impact of a non-responder status to hepatitis B.

All doses of Heplisav B vaccine will be provided by Dynavax and will be at no cost to the participants. All labs drawn will also be at no cost to the participant.

Study participants will be seen for a total of up to 9 visits with participation in the study lasting approximately 3 months. Visits involving labwork, vaccine administration, and the survey will occur in-person at the University of Louisville International Travel Clinic located in MedCenter One (501 East Broadway, Louisville Kentucky 40202). Visits gathering information regarding adverse reactions to vaccination will occur via telephone call visits as well as during in-person visits after the vaccine dose(s) have been administered.

Study Type

Interventional

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Healthcare personnel age 18-64 years of age who have documentation of prior receipt of two rounds of the traditional 3-dose series of Hepatitis B vaccine and having serologic testing demonstrating quantitative Hepatitis B antibody level of less than 10 iU and a negative Hepatitis B antigen.

Exclusion Criteria:

  1. Pregnancy
  2. Allergy to the adjuvanted vaccine or a vaccine component
  3. Sensitivity to yeast
  4. Persons unable to provide consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Vaccination

Heplisav B vaccine will be administered to subjects demonstrating completion of two prior series of standard 3-dose Hepatitis B vaccine but still without evidence of seroconversion.

One dose (20 mcg) of vaccine will be administered intramuscularly followed by Hepatitis B quantitative antibody titer 30-60 days later.

If still Hepatitis B antibody negative, a second dose (20 mcg) of vaccine will be administered intramuscularly followed by a Hepatitis B quantitative titer 30-60 days later.

If still no evidence of Hepatitis B immunity (10iU antibody or greater), will be deemed a non-responder to this vaccine
Biological: Adjuvanted Hepatitis B Vaccine
Adjuvanted Hepatitis B vaccine will be provided to healthcare workers previously vaccinated with the standard 3-dose series of Hepatitis B vaccine but who have failed to respond to two complete 3-dose series

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hepatitis B Seroconversion as Measured by Achievement of 10iU/ml on Quantitative Hepatitis B Titer
Time Frame: within 3 months of acceptance into the study
Demonstration of Hepatitis B immunity via achievement of 10iU/ml or greater on quantitative titer following 1 or 2 doses of the adjuvanted Hepatitis B vaccine
within 3 months of acceptance into the study

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Reported Impact of Non-Response Status on Career and Personal Economics as Reported by Healthcare Worker
Time Frame: within 6 months of acceptance into the study
Impact of Hepatitis B non-response status on career and personal economics as perceived by the healthcare worker completing the survey. This includes metrics such as hourly wage, job promotion, career pathway
within 6 months of acceptance into the study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Louisville

Collaborators

Dynavax Technologies Corporation

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

June 1, 2020

Primary Completion (Anticipated)

February 1, 2021

Study Completion (Anticipated)

February 28, 2021

Study Registration Dates

First Submitted

December 10, 2019

First Submitted That Met QC Criteria

May 11, 2020

First Posted (Actual)

May 13, 2020

Study Record Updates

Last Update Posted (Actual)

April 30, 2021

Last Update Submitted That Met QC Criteria

April 27, 2021

Last Verified

April 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 191219

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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