Hepatitis B Vaccine for Hepatitis B

Overseen By Recruitment Specialist

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Rockefeller University

Must not be taking: Systemic corticosteroids, Immunosuppressive, Anticancer, others

Disqualifiers: HIV, Chronic HCV, Pregnancy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 6 months

12 Participants Needed

Trial Summary

What is the purpose of this trial?

Antibodies are the primary mediators of the protection against infection provided by vaccination. Antibodies become most powerful after the B cells that produce them undergo an evolutionary process called affinity maturation, in which antibodies increase their ability to bind to their targets, and thus neutralize pathogens. Affinity maturation occurs in structures within secondary lymphoid organs (for example lymph nodes or tonsils) known as germinal centers. Germinal centers are well known to be triggered by the first dose of vaccines, generating affinity matured plasma cells (B cells that secrete antibody into serum) and memory B cells, which can be converted into plasma cells by booster doses of vaccine. However, it is not fully understood the extent to which memory B cells can return to germinal centers again upon vaccine boosting. Such return would be very important to allow B cells, for example, to adapt to emerging variants of viruses such as influenza or SARS-CoV-2. This study will involve acquiring samples of B cells from germinal centers that form in response to vaccination with the highly effective hepatitis B vaccine. These cells will be analyzed to determine what fraction of them are memory B cells that returned to germinal centers upon boosting, information that is key to knowledge of how vaccine boosters work. Understanding the "rules" that govern how and when memory B cells choose to return to germinal centers in an effective vaccine such hepatitis B could help efforts to develop effective vaccination against more challenging, rapidly mutating viruses, such as influenza, HIV, and hepatitis C.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those who have used certain medications like systemic corticosteroids, immunosuppressive, anticancer, or antituberculosis drugs in the past 6 months. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Hepatitis B Vaccine for Hepatitis B?

Research shows that the Hepatitis B vaccine, particularly HEPLISAV-B, is highly effective, with a seroprotection rate of 90-100% compared to 71-90% for Engerix-B. This means it helps the body build strong protection against the virus, especially in people who usually respond poorly to vaccines, like older adults and those with certain health conditions. ^{1 2 3 4 5}

Is the Hepatitis B vaccine safe for humans?

The Hepatitis B vaccines, including Engerix-B, Euvax-B, and others, have been shown to be safe in various studies involving adults, infants, and children. No serious adverse events were observed, and the vaccines were well tolerated with only mild side effects reported. ^{2 4 5 6 7}

How is the Hepatitis B Vaccine different from other treatments for Hepatitis B?

The Hepatitis B Vaccine, such as HEPLISAV-B, is unique because it requires fewer doses over a shorter period and provides higher and earlier protection compared to other vaccines like Engerix-B. Additionally, Fendrix is an alternative for those who do not respond to Engerix-B, showing effectiveness in healthcare workers who are non-responsive to the standard vaccine. ^{4 5 7 8 9}

Research Team

Gabriel D. Victora, PhD

Principal Investigator

The Rockefeller University

Eligibility Criteria

Healthy individuals aged 18-50, with no history of Hepatitis B infection or vaccination, can join this trial. They shouldn't have had severe reactions to vaccines before, any chronic infections like HCV, allergies to HBV vaccine components, immune disorders, or be on certain medications. Pregnant or breastfeeding individuals are excluded.

Inclusion Criteria

I have never had hepatitis B nor been vaccinated against it.

I am either male or female.

Exclusion Criteria

I have chronic hepatitis C.

I have tested positive for hepatitis B antibodies.

I am HIV positive.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the Hepatitis B Vaccine (Recombinant) 20 mcg intramuscular injection at 0-1-6 months

6 months

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the third dose of the HBV vaccine

4 weeks

Treatment Details

Interventions

• Hepatitis B Vaccine

Trial Overview The study is testing the response of germinal centers in lymphoid organs to the Hepatitis B vaccine (Recombinant). It aims to understand how memory B cells react and adapt when boosted by vaccines—a key factor for improving vaccinations against mutating viruses.

Participant Groups

Group I: Hepatitis B Vaccine (Recombinant) Experimental Treatment 1 Intervention

Hepatitis B Vaccine (Recombinant) 20 mcg intramuscular injection at 0-1-6 months

Hepatitis B Vaccine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Engerix-B for:

• Prevention of infection caused by all known subtypes of hepatitis B virus

Approved in United States as Heplisav-B for:

• Prevention of infection caused by all known subtypes of hepatitis B virus in adults 18 years of age and older

Approved in United States as Recombivax HB for:

• Prevention of infection caused by all known subtypes of hepatitis B virus

Approved in United States as Twinrix for:

• Prevention of infection caused by hepatitis A and hepatitis B viruses

Approved in European Union as Engerix-B for:

• Prevention of infection caused by all known subtypes of hepatitis B virus

Approved in European Union as Heplisav-B for:

• Prevention of infection caused by all known subtypes of hepatitis B virus in adults 18 years of age and older

Approved in European Union as Prehevbrio for:

• Prevention of infection caused by all known subtypes of hepatitis B virus

Approved in Canada as Engerix-B for:

• Prevention of infection caused by all known subtypes of hepatitis B virus

Who Is Running the Clinical Trial?

Rockefeller University

Lead Sponsor

Trials

162

Recruited

16,700+

Weill Medical College of Cornell University

Collaborator

Trials

1,103

Recruited

1,157,000+

Findings from Research

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 involving 105 healthy infants, both the new recombinant hepatitis B vaccine (Hepavax-Gene) and the standard Engerix-B vaccine demonstrated over 94% effectiveness in providing seroprotection against hepatitis B within 360 days.

The safety profiles of both vaccines were comparable, with no serious adverse events reported, and very few subjects remained HBsAg positive after 2 years, indicating strong long-term protection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy, safety and immunogenicity of Hepavax-Gene and Engerix-B, recombinant hepatitis B vaccines, in infants born to HBsAg and HBeAg positive mothers in Vietnam: an assessment at 2 years. Hieu, NT., Kim, KH., Janowicz, Z., et al.[2019]

In a study of 64 people with HIV who received the Heplisav-B vaccine, the seroprotection rate (SPR) was 81%, indicating that the vaccine is effective in providing protection against hepatitis B in this population.

The SPR was particularly high (86%) in individuals without significant non-HIV immunosuppression, suggesting that Heplisav-B could be a viable option for HBV vaccination in people with HIV, especially those with better immune function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brief Report: Heplisav-B Seroprotection in People With HIV: A Single-Center Experience. Schnittman, SR., Zepf, R., Cocohoba, J., et al.[2022]

A clinical trial involving 400 healthy adults demonstrated that four hepatitis B vaccines, including Heberbiovac-HB, Euvax-B, Hepavax-Gene, and Engerix-B, were safe and highly immunogenic, achieving similar seroprotection rates of around 96-100% after the second and third doses.

Heberbiovac-HB showed significantly higher antibody levels and responder rates compared to the other vaccines, indicating it may provide a stronger immune response, although all vaccines were well tolerated with no serious adverse events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of four recombinant hepatitis B vaccines applied on an accelerated schedule in healthy adults. Hernández-Bernal, F., Aguilar-Betancourt, A., Aljovin, V., et al.[2011]

Both the Euvax-B and Engerix-B hepatitis B vaccines were found to be well tolerated and highly effective, with seroprotection rates exceeding 90% in all groups of 300 newborns studied.

Euvax-B was shown to be clinically identical to Engerix-B, meaning it can be safely used interchangeably in a vaccination schedule, allowing flexibility in immunizing infants against hepatitis B.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of two recombinant hepatitis B vaccines and their interchangeability in Argentine infants. Tregnaghi, M., Ussher, J., Baudagna, AM., et al.[2019]

The new recombinant hepatitis B vaccine (Bio-Hep-B) at a reduced dose of 2.5 micrograms was found to be as safe as the standard 10 microgram dose of the licensed vaccine (Engerix-B) in a study involving 217 children aged 4-9 years.

While Bio-Hep-B showed a trend towards better immunogenicity at early time points, both vaccines produced similar antibody responses, indicating that the lower dose of Bio-Hep-B is effective for immunization against hepatitis B.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of a novel mammalian cell-derived recombinant hepatitis B vaccine containing Pre-S1 and Pre-S2 antigens in children. Raz, R., Dagan, R., Gallil, A., et al.[2019]

In a study involving healthcare workers who did not respond to the Engerix B® vaccine, the Fendrix® adjuvanted vaccine demonstrated a 92.3% success rate in developing humoral immunity against Hepatitis B after a specific vaccination schedule.

The Fendrix® vaccine showed a significant increase in antibody levels after the initial doses, suggesting it could be a viable alternative for immunizing healthcare workers against HBV who are nonresponsive to traditional vaccination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fendrix® Vaccine Effectiveness in Healthcare Workers Who Are Non-Responsive to Engerix B® Vaccination. Tejada-Pérez, JJ., Vázquez-Vicente, JJ., Herrera-Burgos, MR., et al.[2021]

HEPLISAV™ provides higher and earlier seroprotection rates (89-96%) compared to Engerix-B (62-81%) with fewer doses required, making it a more efficient vaccination option for preventing hepatitis B infection in various populations.

The cost-effectiveness analysis showed that HEPLISAV is economically favorable, with incremental cost-effectiveness ratios under $25,000 for all studied groups, and it was even cost-saving for patients with chronic or end-stage kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of hepatitis B vaccination using HEPLISAV™ in selected adult populations compared to Engerix-B® vaccine. Kuan, RK., Janssen, R., Heyward, W., et al.[2022]

Engerix-B is a safe and well-tolerated recombinant DNA vaccine that effectively immunizes against all known subtypes of the hepatitis B virus.

The vaccine produces anti-HBs antibody responses that are comparable to those generated by traditional plasma-derived hepatitis B vaccines, indicating its efficacy in providing immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engerix-B hepatitis B vaccine (recombinant)/Smith, Kline & French. Swartz, ML.[2007]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. Netherlands pubmed.ncbi.nlm.nih.gov

Comparative efficacy, safety and immunogenicity of Hepavax-Gene and Engerix-B, recombinant hepatitis B vaccines, in infants born to HBsAg and HBeAg positive mothers in Vietnam: an assessment at 2 years. [2019]

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

Brief Report: Heplisav-B Seroprotection in People With HIV: A Single-Center Experience. [2022]

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

Comparison of four recombinant hepatitis B vaccines applied on an accelerated schedule in healthy adults. [2011]

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

Comparison of two recombinant hepatitis B vaccines and their interchangeability in Argentine infants. [2019]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of a novel mammalian cell-derived recombinant hepatitis B vaccine containing Pre-S1 and Pre-S2 antigens in children. [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Fendrix® Vaccine Effectiveness in Healthcare Workers Who Are Non-Responsive to Engerix B® Vaccination. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of hepatitis B vaccination using HEPLISAV™ in selected adult populations compared to Engerix-B® vaccine. [2022]

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

Engerix-B hepatitis B vaccine (recombinant)/Smith, Kline & French. [2007]