TLR-9 Adjuvanted Vaccination for Chronic Hepatitis B (BOOST-9)

Augmentation of Humoral Immunity Using Toll-Like Receptor (TLR) 9 Adjuvanted HBV Surface Antigen to Enhance Anti-HBSAg Response

The goal of this clinical trial is to learn if HEPLISAV-B, a vaccine that is approved to prevent hepatitis B infection in people that are not already infected, is safe in people already chronically infected with hepatitis B. The main quiestions it aims to answer are:

1. Is HEPLISAV-B safe in people with chronic hepatitis B?
2. What side effects, if any, could HEPLISAV-B cause in people with chronic hepatitis B?
3. How does HEPLISAV-B affect the cells that fight chronic hepatitis B?

Participants will:

• Receive HEPLISAV-B as an injection in the muscle, one injection every 4 weeks, for a total of 2 injections.
• Visit the clinic a total of 5 times, and have 3 phone follow ups over 14 months.
• Be asked if they are having any side effects from HEPLISAV-B.
• Have blood samples collected.

Study Overview

• Status: Recruiting
• Conditions: Hepatitis B; Chronic Hepatitis B
• Intervention / Treatment: Drug: Hepatitis B Vaccine Recombinant, Adjuvanted Intramuscular Solution [HEPLISAV-B]

Detailed Description

Ten people with chronic hepatitis B and virally suppressed on nucleos(t)ide analogue (NUC) therapy will receive a total of two 0.5ml intramuscular injections of HEPLISAV-B, a CpG-adjuvanted vaccine, the first injection on day 0, and the second injection on week 4.

Participants will visit the clinic on day 0, and weeks 2, 4, 8, and 28. They will also have phone follow ups on day 7, and weeks 5 and 56. At each follow up, participants will be asked about any side effects. At each clinic visit blood samples will be collected. For 7 days after each HEPLISAV-B injection, participants will complete a diary to document any reactions to the injection.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Lydia Tang, MBChB; Phone Number: (410) 706-6567; Email: LydiaTang@IHV.umaryland.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • Institute of Human Virology, University of Maryland School of Medicine
      • Contact: Lydia Tang, MBChB; Phone Number: (410) 706-6567; Email: LydiaTang@IHV.umaryland.edu
      • Contact: Lisa Anderson, RN, BS; Phone Number: 4107064069; Email: lisa.anderson@ihv.umaryland.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

In order to participate in this study, an individual must meet all the following criteria:

1. >18 years old
2. Diagnosed with CHB infection, without HIV, hepatitis C nor hepatitis D co-infections
3. Currently receiving NUC with HBV VL <100 IU/ml for ≥ 12 months
4. Willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, and other study procedures.
5. Determined by medical history, targeted physical examination, and clinical judgement of the investigator to be in good health.

CHB infection is defined as any individual with documentation of a positive HBsAg and/or detectable HBV DNA test for at least 6 months.

Exclusion Criteria:

A participant will be ineligible to participate on this study if any of the following criteria are met:

1. Pregnancy or breast feeding.
2. Received systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to Screening (for corticosteroids ≥ 20 mg/day of prednisone equivalent). Received anti-CD20 immunosuppressant within 12 months of screening. Topical tacrolimus is allowed if not used within 14 days prior to Day 1.
3. Received or plans to receive live virus vaccines within 4 weeks, and inactivated vaccine within 2 weeks prior to randomization; or plans to receive a non-study vaccine within 28 days after any dose of study vaccine (with exception for seasonal influenza vaccine within 14 days of study vaccine).
4. Administration of any blood products within 3 months prior to randomization.
5. Participation in a study with an investigational study product or device within 30 days of randomization.
6. Has allergies to any hepatitis B and/or yeast-based vaccines.

7. Subjects meeting any of the following laboratory parameters at screening:

   1. ALT greater than 3 times the upper limit of normal
   2. Elevated total bilirubin WITH direct bilirubin greater than 2 times upper limit of normal
8. Is acutely ill or febrile 72 hours prior to or at vaccine dosing (fever defined as ≥ 38.0°C/100.4°F). Participants meeting this criterion may be rescheduled within the relevant window periods. Afebrile participants with minor illnesses can be enrolled at the discretion of the investigator.
9. Have any chronic or acute or unstable conditions that the investigator considers a contraindication to study participation.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Intervention; HEPLISAV-B is available in pre-filled, single-dose 0.5 mL vials. Each dose contains 20 μg of HBsAg and 3,000 μg of 1018 adjuvant. HEPLISAV-B is administered as an intramuscular injection in the deltoid region. Study subjects will receive a total of 2 injections, each administered at least 4 weeks apart - the same dosing schedule recommended for hepatitis B prevention. Once enrolled, participants will have study visits on days 0 (first injection), and weeks 2, 4 (second injection), 8, and 28. They will also have phone follow ups on day 7 and week 5 (7 days after each injection) and week 56 (end of study).

Drug: Hepatitis B Vaccine Recombinant, Adjuvanted Intramuscular Solution [HEPLISAV-B]; one 0.5ml intramuscular injection on day 0 and week 4.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and reactogenicity of the Hepatitis B Virus Surface Antigen, Recombinant (HEPLISAV-B; Dynavax Technologies Corporation) Vaccine in patients with chronic hepatitis B	Number of local and systemic solicited adverse events	Baseline to 7 days following each vaccine dose
Occurence of unsolicited adverse events	Number of unsolicited adverse events	from dose 1 to 28 days following each vaccine dose
Medically Attended Adverse Events	Number of Medically Attended Adverse Events (MAAEs)	From first vaccine to 12 months after last vaccine on study.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-HBsAg Seroconversion	Number of patients with anti-HBsAg seroconversion	Day 0 through 12 months post vaccination
Change in hepatitis B surface antigen levels	Hepatitis B surface antigen levels (international units per milliliter, IU/mL) will be measured at baseline, and thoughout study	Day 0 to week 28
Changes in immunologic and virologic responses throughout study	Change in hepatitis B surface antigen-specific immune cell types (percentage of cells) and function (percentage of cells producing cytokines), and hepatitis B virus viral markers (international units per milliliter, IU/mL) will be evaluated at baseline, and throughout the study.	baseline to week 28

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Investigators: Principal Investigator: Lydia Tang, MBChB, University of Maryland, Baltimore

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2025
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: April 6, 2021
• First Submitted That Met QC Criteria: April 9, 2021
• First Posted (Actual): April 14, 2021

Study Record Updates

• Last Update Posted (Estimated): October 20, 2025
• Last Update Submitted That Met QC Criteria: October 16, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: vaccine; hepatitis B; HBsAg; Toll-like receptor; hepatitis B surface antibody; HBsAb; anti-HBsAg; hepatitis B surface antigen; TLR9; CpG
• Additional Relevant MeSH Terms: Blood-Borne Infections; Pathologic Processes; Chronic Disease; Disease Attributes; Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Communicable Diseases; DNA Virus Infections; Hepadnaviridae Infections; Hepatitis, Chronic; Hepatitis; Pathological Conditions, Signs and Symptoms; Hepatitis B; Hepatitis B, Chronic; Biological Products; Complex Mixtures; Vaccines; Viral Vaccines; Viral Hepatitis Vaccines; Heplisav-B; Hepatitis B Vaccines
• Other Study ID Numbers: HP-00115083

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No