Adjuvanted vs Traditional Vaccines for Hepatitis B

Overseen By Ramin Herati, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: NYU Langone Health

Must not be taking: Immune-suppressing medications

Disqualifiers: Chronic HBV, Pregnancy, Anemia, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 4 weeks

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two types of hepatitis B vaccines to determine which is more effective for individuals who typically do not respond well to the traditional vaccine. It examines the traditional vaccine and a new version with an added ingredient called CpG, an adjuvant that enhances the body's immune response. This could improve hepatitis B vaccines and others in the future. Individuals who have struggled with hepatitis B vaccine responses or have conditions like HIV/AIDS, which can lead to poor vaccine responses, might be suitable candidates for this trial. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, and this research aims to understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have used immune-suppressing medications in the 30 days before joining.

What is the safety track record for these treatments?

Research has shown that the CpG-adjuvanted hepatitis B vaccine, HEPLISAV-B, is safe for people. Studies have found no harmful effects during pregnancy for those who received this vaccine, suggesting safety across different groups. This vaccine strengthens the immune system and requires only two doses over one month, offering more convenience than traditional vaccines that often need more doses.

The traditional hepatitis B vaccine is widely used and has a strong safety record, but some people do not respond well to it. This trial compares the two vaccines to better understand their mechanisms and why some individuals may not respond to the traditional vaccine. Past studies have demonstrated the safety of both vaccines, but this trial will clarify their differences in effectiveness and immune response. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

The CpG-adjuvanted HBV vaccine is unique because it uses an adjuvant called CpG to enhance the body's immune response. Unlike traditional hepatitis B vaccines, which rely solely on the virus's antigens to provoke immunity, the CpG adjuvant activates specific parts of the immune system, potentially leading to a stronger and faster response. Researchers are excited about this approach because it could provide more effective protection, particularly for individuals who do not respond well to traditional vaccines. This innovation may lead to improved vaccine efficacy, helping to reduce the incidence of hepatitis B more effectively.

What evidence suggests that this trial's vaccines could be effective for hepatitis B?

This trial will compare the CpG-adjuvanted HBV vaccine, known as Heplisav-B, with traditional HBV vaccines. Research has shown that the CpG-adjuvanted HBV vaccine effectively prevents hepatitis B. Studies have found that this vaccine can provide protection with fewer doses than traditional vaccines. In one study, it was 19.6% more effective at creating protective immunity. The CpG adjuvant boosts the immune system, leading to this improved response. The safety of this vaccine is similar to that of traditional vaccines. Overall, the CpG-adjuvanted HBV vaccine offers a more effective option for preventing hepatitis B, especially for those who have had trouble responding to traditional vaccines. ^{2 6 7 8 9}

Who Is on the Research Team?

Ramin Herati, MD

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

This trial is for adults who can consent to participate and are generally healthy. It's not for those with chronic Hepatitis B, pregnant individuals, people with significant anemia or blood clotting issues, anyone on immune-suppressing drugs recently, or if the investigator thinks it's unsafe for them.

Inclusion Criteria

Must be able to understand and sign the Informed Consent Form (ICF)

Exclusion Criteria

Pregnancy

I haven't taken immune-suppressing drugs in the last 30 days.

Any condition that, in the opinion of the Investigator, would make study participation unsafe or would interfere with the objectives of the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either the traditional HBV vaccine or the CpG-adjuvanted HBV vaccine

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person) at Month 1 post-final dose

What Are the Treatments Tested in This Trial?

Interventions

• CpG-adjuvanted HBV Vaccine
• Traditional HBV Vaccine

Trial Overview The study compares two types of hepatitis B vaccines: the traditional one and a new CpG-adjuvanted vaccine designed to improve immune response. The goal is to understand why some people don't respond well to the current vaccine.

How Is the Trial Designed?

Group I: CpG-adjuvanted HBV Vaccine Experimental Treatment 1 Intervention

Group II: Traditional HBV Vaccine Active Control 1 Intervention

CpG-adjuvanted HBV Vaccine is already approved in United States, European Union for the following indications:

Approved in United States as HEPLISAV-B for:

• Prevention of hepatitis B infection in adults 18 years of age and older

Approved in European Union as CpG-adjuvanted Hepatitis B Vaccine for:

• Prevention of hepatitis B infection in adults

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

In a study involving over 69,000 adults, HepB-CpG (Heplisav-B) showed no significant safety concerns compared to HepB-alum (Engerix-B) regarding new-onset immune-mediated diseases, herpes zoster, or anaphylaxis.

The incidence of rheumatoid arthritis was initially higher in HepB-CpG recipients, but after further review, this difference was not statistically significant, indicating that HepB-CpG is likely safe for use in the general population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-licensure safety study of new-onset immune-mediated diseases, herpes zoster, and anaphylaxis in adult recipients of HepB-CpG vaccine versus HepB-alum vaccine. Ackerson, B., Sy, LS., Slezak, J., et al.[2023]

In a study of 120 adults with HIV, the novel Heplisav-B (HepB-CpG) vaccine demonstrated a significantly higher seroconversion rate of 93.4% compared to 57.6% for the conventional Engerix-B (HepB-alum) vaccine, indicating better efficacy in providing protection against hepatitis B virus.

The study suggests that individuals without diabetes were more likely to respond positively to the HBV vaccination, highlighting the importance of considering underlying health conditions when evaluating vaccine responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Observational Study Evaluating the Seroprotection of HepB-alum Vaccine and HepB-CpG Vaccine in People With HIV. Reilly-Evans, B., Dudzik, B., Costlow, DJ., et al.[2023]

HEPLISAV-B, a new hepatitis B vaccine, demonstrated a superior seroprotection rate of 90-100% in 7,056 subjects compared to 71-90% for the traditional Engerix-B vaccine, particularly benefiting populations with poor vaccine responses like older adults and diabetics.

The safety profile of HEPLISAV-B was comparable to Engerix-B across 9,871 subjects, making it a promising option due to its higher efficacy, shorter two-dose regimen, and earlier seroprotection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CpG-Adjuvanted Hepatitis B Vaccine (HEPLISAV-B®) Update. Lee, GH., Lim, SG.[2022]

In a study of 69,625 adults, the HepB-CpG vaccine (Heplisav-B) did not show an increased risk of acute myocardial infarction (MI) compared to the HepB-alum vaccine (Engerix-B), with a lower rate of MI events observed in the HepB-CpG group (1.67 per 1000-person-years) versus the HepB-alum group (1.86 per 1000-person-years).

The study confirmed that the HepB-CpG vaccine is noninferior in terms of safety regarding MI risk, suggesting it can be a safe alternative to the traditional 3-dose hepatitis B vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association Between 2-Dose vs 3-Dose Hepatitis B Vaccine and Acute Myocardial Infarction. Bruxvoort, K., Slezak, J., Qian, L., et al.[2022]

The HepB-CpG vaccine, requiring only 2 doses, induces significantly higher and faster immune responses in adults compared to the traditional 3-dose Engerix-B vaccine, making it particularly beneficial for those at risk of poor vaccine response.

While the safety profile of HepB-CpG is generally comparable to Engerix-B, there are concerns about higher rates of acute myocardial infarction and other serious events, indicating the need for further safety evaluations in the general population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heplisav-B: A Hepatitis B Vaccine With a Novel Adjuvant. Champion, CR.[2021]

The Heplisav-B vaccine (HepB-CpG) is highly effective, achieving seroprotective antibody levels in 90.0%-100.0% of adults, compared to 70.5%-90.2% for the traditional Engerix-B vaccine, based on data from four randomized controlled trials.

Administered as a 2-dose series over 1 month, Heplisav-B offers a convenient and effective option for preventing hepatitis B virus infections in individuals aged 18 and older.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recommendations of the Advisory Committee on Immunization Practices for Use of a Hepatitis B Vaccine with a Novel Adjuvant. Schillie, S., Harris, A., Link-Gelles, R., et al.[2019]

Citations

1. cdc.gov cdc.gov/acip/grade/hepb.html

HEPLISAV-B | ACIP Based on the available immunogenicity evidence, a 2-dose schedule (0, 1 month) of HepB-CpG will be efficacious for the prevention of HBV infection.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3906263/

The potential of 1018 ISS adjuvant in hepatitis B vaccines In Phase III clinical trials, HEPLISAV™ has been shown to elicit seroprotective antibody titers with fewer immunizations. Similar safety profiles are ...

3. heplisavbhcp.com heplisavbhcp.com/heplisav-b-study-results/

Study Results - HEPLISAV-B® (Recombinant), Adjuvanted 19.6% (95% CI, 14.7–24.8) difference in protective immunity between patient groups at primary endpoint · The primary analysis compared the rate of protective ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0264410X25000027

The role of HepB-CpG (Heplisav-B) vaccination schedule Heplisav-B, a CpG-adjuvanted recombinant HBV vaccine, has achieved an improved vaccination rate and higher HBsAb in the general population ...

5. heplisavbhcp.com heplisavbhcp.com/heplisav-b-dosing/

Dosing Efficiency - Heplisav-B Series completion within the recommended vaccine schedule plus 3 months (45% for HEPLISAV‑B and 26% for Engerix‑B) was the primary outcome and series completion ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39222955/

Post-marketing safety study to evaluate pregnancy ... The study found no evidence of adverse pregnancy outcomes for recipients of HepB-CpG in comparison to HepB-alum.

7. heplisavb.com heplisavb.com/

Hepatitis B Vaccine - HEPLISAV-B® (Recombinant), Adjuvanted HEPLISAV-B provides protection with 2 doses in 1 month. The first and only adult hepatitis B vaccine that is only 2 doses in 1 month.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33783302/

CpG-Adjuvanted Hepatitis B Vaccine (HEPLISAV-B®) ... HEPLISAV-B is a hepatitis B vaccine composed of rHBsAg mixed with a synthetic oligonucleotide containing CpG motifs that stimulate innate immunity through TLR9.

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0264410X22004431

Safety and immunogenicity of HepB-CpG in women with ... These limited data suggest that HepB-CpG is immunogenic in women who become pregnant after vaccination, and pregnancy outcomes appear to be similar to women ...