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

• ClinicalTrials.gov Identifier: NCT04385524
• Recruitment Status: Not yet recruiting
• First Posted: May 13, 2020
• Last Update Posted: May 13, 2020
• Sponsor: University of Louisville
• Collaborator: Dynavax Technologies Corporation
• Information provided by (Responsible Party): Ruth Carrico, University of Louisville

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hepatitis B Virus	Biological: Adjuvanted Hepatitis B Vaccine	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Use of Dynavax Heplisav B in Healthcare Workers Previously Vaccinated With Standard 3-dose Vaccine Who Failed to Demonstrate Seroprotection
• Estimated Study Start Date: June 1, 2020
• Estimated Primary Completion Date: February 1, 2021
• Estimated Study Completion Date: February 28, 2021

Arms and Interventions

Arm

Intervention/treatment

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

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Contacts

Contact: Ruth Carrico, PhD DNP; 502-640-8026; ruth.carrico@louisville.edu

Sponsors and Collaborators

University of Louisville

Dynavax Technologies Corporation

More Information

• Responsible Party: Ruth Carrico, Professor, University of Louisville
• ClinicalTrials.gov Identifier: NCT04385524
• Other Study ID Numbers: 191219
• First Posted: May 13, 2020
• Last Update Posted: May 13, 2020
• Last Verified: December 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Ruth Carrico, University of Louisville:

Hepatitis B vaccine; Hepatitis B vaccine non-responder; Hepatitis B seroconversion

Additional relevant MeSH terms:

Hepatitis B; Hepatitis; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Hepadnaviridae Infections; DNA Virus Infections