HEPLISAV-B (TLR‑9 adjuvanted) vaccine for adults with chronic hepatitis B

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

This trial will try giving two HEPLISAV-B vaccine shots to adults with chronic hepatitis B who are virally suppressed on antiviral therapy to see if the vaccine is safe and how it affects their immune cells.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Maryland, Baltimore (Academic / other)
• Drugs / interventions: prednisone
• Locations: 1 site (Baltimore, Maryland)
• Trial ID: NCT04843852 on ClinicalTrials.gov

What this trial studies

This Phase 1 trial enrolls ten adults with chronic hepatitis B who have been virally suppressed on nucleos(t)ide analogue (NUC) therapy. Participants receive two 0.5 mL intramuscular doses of HEPLISAV-B (a CpG/TLR‑9–adjuvanted vaccine) on day 0 and week 4, with clinic visits and blood draws at specified intervals and short-term symptom diaries after each injection. The study’s primary focus is safety and characterization of immune-cell responses following vaccination. Follow-up includes five clinic visits over 28 weeks and additional phone checks out to week 56.

Who should consider this trial

Good fit: Ideal candidates are adults (over 18) with chronic hepatitis B who are on stable NUC therapy with hepatitis B viral load <100 IU/mL for at least 12 months, without HIV, hepatitis C, or hepatitis D co-infection, and who can attend all visits.

Not a fit: People with active viremia, coinfections (HIV, HCV, HDV), recent or ongoing immunosuppression, pregnancy or breastfeeding, or who are not on stable NUC therapy are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, the vaccine could boost HBV-specific immune responses and inform future therapies aimed at improving viral control or achieving a functional cure.

How similar studies have performed: Using HEPLISAV-B as a therapeutic vaccine for chronic HBV is largely untested—HEPLISAV-B is approved for prevention, and TLR‑9–adjuvanted vaccines have shown immune activation in other settings but not established therapeutic success in chronic HBV.

Eligibility criteria

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.

Where this trial is running

Baltimore, Maryland

• Institute of Human Virology, University of Maryland School of Medicine — Baltimore, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Lydia Tang, MBChB — University of Maryland, Baltimore
• Study coordinator: Lydia Tang, MBChB

Conditions Hepatitis B; Chronic Hepatitis B; hepatitis B; Toll-like receptor; vaccine; hepatitis B surface antibody; HBsAb; anti-HBsAg