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

Trial Summary

What is the purpose of this trial?

Vaccines have prevented countless infections but poor vaccine responses remain a major challenge in many scenarios. Hepatitis B vaccine nonresponses are common but immunologically not well-understood. This study aims to study the immunology of hepatitis B vaccine responses by comparing traditional HBV vaccine, which is associated with nonresponses in some patients, to CpG-adjuvanted HBV vaccine, which is associated with far fewer rates of nonresponses. This research will build upon prior studies of the human immune response to infection to gain a deeper understanding of the complexity of these responses. This information will be broadly useful as many vaccine candidates fail due to lack of immunogenicity, potentially enabling improved vaccine design and better protection.

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 data supports the effectiveness of the treatment Heplisav-B for Hepatitis B?

Heplisav-B, a hepatitis B vaccine with a novel adjuvant, has shown superior effectiveness compared to traditional vaccines like Engerix-B. In studies, 90-100% of people who received Heplisav-B developed protective antibodies, compared to 71-90% with Engerix-B, especially benefiting those who typically respond poorly to vaccines, such as older adults and people with chronic conditions. ^{1 2 3 4 5}

Is the CpG-adjuvanted Hepatitis B vaccine safe for humans?

The CpG-adjuvanted Hepatitis B vaccine, known as HEPLISAV-B, has been shown to have a similar safety profile to traditional vaccines like Engerix-B in studies involving thousands of participants. It has been evaluated for safety in both clinical trials and post-marketing studies, with no significant increase in adverse events compared to traditional vaccines. ^{1 2 3 5 6}

How does the CpG-adjuvanted HBV vaccine differ from traditional hepatitis B vaccines?

The CpG-adjuvanted HBV vaccine (Heplisav-B) is unique because it uses a novel adjuvant that stimulates the immune system more effectively, requires only two doses over one month, and provides higher protection rates, especially in people who typically respond poorly to vaccines, compared to traditional three-dose vaccines like Engerix-B. ^{1 2 3 4 5}

Research Team

Ramin Herati, MD

Principal Investigator

NYU Langone Health

Eligibility Criteria

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)

I am 18 years old or older.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

References

1. Netherlands 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. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Observational Study Evaluating the Seroprotection of HepB-alum Vaccine and HepB-CpG Vaccine in People With HIV. [2023]

3. England pubmed.ncbi.nlm.nih.gov

CpG-Adjuvanted Hepatitis B Vaccine (HEPLISAV-B®) Update. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Association Between 2-Dose vs 3-Dose Hepatitis B Vaccine and Acute Myocardial Infarction. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Recommendations of the Advisory Committee on Immunization Practices for Use of a Hepatitis B Vaccine with a Novel Adjuvant. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

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