Hepatitis B Vaccine for Hepatitis B

Recruiting in Palo Alto (17 mi)

Overseen by Gabriel D. Victora, PhD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Rockefeller University

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

Disqualifiers: HIV, Chronic HCV, Pregnancy, others

No Placebo Group

Prior Safety Data

Approved in 8 Jurisdictions

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}

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 am between 18 and 50 years old.

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.

Trial 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 (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, United States, United States, United States, European Union, European Union, 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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

The Rockefeller University New York, NY

Who Is Running the Clinical Trial?

Rockefeller University Lead Sponsor

Weill Medical College of Cornell University Collaborator

References

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

CpG-Adjuvanted Hepatitis B Vaccine (HEPLISAV-B®) Update. [2022] Introduction: HEPLISAV-B is a hepatitis B vaccine composed of rHBsAg mixed with a synthetic oligonucleotide containing CpG motifs that stimulate innate immunity through TLR9. This vaccine was recently approved by FDA in view of its superior efficacy.Areas covered: Published literature on HEPLISAV-B was critically reviewed. Four randomized controlled trials among 7,056 subjects receiving 2 doses of HEPLISAV-B and 3,214 subjects receiving 3 doses of Engerix-B showed superior seroprotection rate (SPR) (anti-HBs ≥10 mIU/mL) of 90-100%, compared with 71-90% in those receiving Engerix-B. Furthermore, the seroprotection rate was also significantly higher in HEPLISAV-B compared with Engerix-B recipients in persons with traditionally poor vaccine responses such as older adults, diabetics, and those with chronic kidney disease. The safety profiles among 9,871 subjects were similar between HEPLISAV-B and Engerix-B .Expert opinion: HEPLISAV-B, a CpG adjuvant mixed with HBsAg, is more efficacious and produced earlier seroprotection compared to existing vaccines, with a favorable safety profile. The shorter, two-dose regimen, earlier seroprotection, higher adherence, and a higher seroprotection rate, especially in populations with traditionally poor vaccine response, makes this an important therapeutic option in hepatitis B vaccination.

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] In a randomized, controlled trial, 105 healthy full-term infants born to HBsAg and HBeAg positive mothers received three doses (at 0, 1 and 6 months) of either a new recombinant hepatitis B vaccine (Hepavax-Gene) or Engerix-B. Both groups were also given hepatitis B specific Hepa-big immunoglobulin (HBIG) within 24h of birth. Levels of antibodies to hepatitis B surface antigen (anti-HBs) were assessed on days 30, 60, 210, 360, and 2 years post-vaccination. Efficacy and immunogenicity and safety of the two vaccines were not significantly different; both vaccines achieved >94% seroprotection within 360 days. At 2 years, only one subject (1.9%) in the Hepavax-Gene group and two subjects (3.9%) in the Engerix-B group were HBsAg positive. No serious adverse events (AEs) were observed in either group.

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

Brief Report: Heplisav-B Seroprotection in People With HIV: A Single-Center Experience. [2022] Heplisav-B, a hepatitis B virus (HBV) vaccine with an immunostimulatory adjuvant, was FDA approved in 2017 for adults ≥18 years. In randomized controlled trials, Heplisav-B demonstrated seroprotection rates (SPR) of 90%-95% versus 65%-80% for Engerix-B. No studies have included people with HIV (PWH), and the SPR and its predictors in this population are unknown.

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

Comparison of four recombinant hepatitis B vaccines applied on an accelerated schedule in healthy adults. [2011] A post-marketing, double blind, randomised, controlled clinical trial to assess the immunogenicity and safety profiles of four commercially available recombinant hepatitis B vaccines was performed. The vaccines included in this study were Heberbiovac-HB (®) (Heber Biotec S.A., Havana, Cuba), Euvax-B (®) (LG Chemical Ltd., Seoul, Korea), Hepavax-Gene (®) (Greencross Vaccine Corp., Seoul, Korea), and Engerix-B (®) (GlaxoSmithKline Biologicals, Rixensart, Belgium). Vaccines were administered intramuscularly to healthy adults in three 20mg doses at monthly intervals (0 - 1 - 2 months). Four hundred volunteers aged 18 to 45 years (average age, 35 years) non-reactive for serological markers of hepatitis B virus infection were vaccinated. Volunteers were randomly assigned (ratio 1:1:1:1) to one of the four treatment groups. The antibody response (anti-HBs) was assessed at days 60, 90 and 365 post-vaccination using a commercial kit. The four vaccines showed to be safe and highly immunogenic. Similar seroprotection rates (anti-HBs ≥10 IU/L) about one month after application of the second and third dose were obtained for Engerix-B (®) , Hepavax-Gene (®) , Euvax-B (®) , and Heberbiovac-HB (®) vaccines 96.7%, 96.6%, 100%, 100% and 98.8%, 89.5%, 100%, 100%, respectively.. Heberbiovac-HB (®) vaccine achieved significantly higher geometric mean antibody titers (GMT) and rate of good and hyper-responders at all time-points post-vaccination. The GMT on day 365 after full vaccination was significantly reduced in all groups compared to day 90, although Heberbiovac-HB (®) showed the highest anti-HBs GMT and good-responders rate. The four vaccines were well tolerated and poorly reactogenic. No serious adverse events were observed. This study confirms an overall good immune response and rapid priming for the four vaccines in the course of an accelerated schedule, with higher anti-HBs geometric mean concentrations and better responses for Heberbiovac-HB (®) . [WHO primary Registry Number: RPCEC00000075].

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

Comparison of two recombinant hepatitis B vaccines and their interchangeability in Argentine infants. [2019] To compare two pediatric recombinant hepatitis B vaccines-the Engerix-B reference vaccine and the Euvax-B vaccine-in terms of immunogenicity and reactogenicity, and also to investigate their interchangeability, that is, whether a three-dose hepatitis B vaccination schedule begun with a first dose of Engerix-B could be completed with two doses of Euvax-B.

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] We tested the safety and immunogenicity of the new recombinant hepatitis B virus (HBV) vaccine produced via expression of the Pre-S1, Pre-S2 and S protein components of the hepatitis B surface antigen (HBsAg). A reduced dose (2.5 micrograms) of the vaccine (Bio-Hep-B) was tested in children aged 4-9 years and was compared to a 10 microgram dose of a licensed vaccine (Engerix-B) in a randomized manner. Both vaccines were administered in 3 doses (0, 1 and 6 month intervals). Adverse events were collected 5 days following each vaccination by a diary card provided to the parents. Immunogenicity was tested by measuring anti-hepatitis B surface antibody (anti-HBs). A total of 217 children were enrolled (162 in the Bio-Hep-B group and 55 in the Engerix-B group). Total adverse events were observed in 35% of the Bio-Hep-B group and 33% of the Engerix-B group, with no differences when each of the potential adverse events was considered. Titers were within the expected range (geometric mean titers post dose 1, 2 and 3 were 45.8, 8360.2 and 1445.7, respectively, for Bio-Hep-B and 36.3, 10316.1 and 1898.7, respectively, for Engerix-B). A trend toward better immunogenicity with Bio-Hep-B was observed at early visits when measured by both seroconversion (anti-HBs > or = 2.1 mIU ml-1) rate and seroprotection (anti-HBs > or = 10 mIU ml-1) rate; however, statistical significance was not reached. We conclude that in children, Bio-Hep-B vaccine at a reduced dose was as safe and as immunogenic as Engerix-B given at the regular pediatric dosage.

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

Fendrix® Vaccine Effectiveness in Healthcare Workers Who Are Non-Responsive to Engerix B® Vaccination. [2021] Hepatitis B (HBV) is a pathogen virus with transmission mechanisms that include contact with the infected blood or bodily fluids of the infected organism. Nowadays, healthcare workers are one of the most exposed groups to HBV. Conventionally, completing a vaccine series dosage with Engerix B® lowers this risk by providing workers with immunity to the virus. However, through the years, we have encountered nonresponsive health personnel to the Engerix B® vaccine; hence, the Occupational Health Service of Poniente Hospital studied the Fendrix® adjuvanted vaccine as an alternative vaccine to develop immunological responses in healthcare workers who do not respond to vaccination with Engerix B®. In our study, we employed a vaccination schedule with the Fendrix® vaccine, performing serology tests on the cases after the application of each dose. The results obtained showed humoral immunity in 92.3% of the cases, with a remarkable increase in antibody titer after the first doses. These encouraging results support the future inclusion of this vaccine as one possible alternative for the immunization to HBV for healthcare workers nonresponsive to Engerix B®.

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] HEPLISAV™ is an adult hepatitis B vaccine that requires fewer doses over a shorter period of time and elicits higher and earlier seroprotection compared to Engerix-B to reduce the risk of hepatitis B infection. The objective of this analysis was to evaluate the cost-effectiveness of vaccination with HEPLISAV vs. Engerix-B(®) to prevent hepatitis B infection in select populations.

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

Engerix-B hepatitis B vaccine (recombinant)/Smith, Kline & French. [2007] Engerix-B [Hepatitis B Vaccine (Recombinant)], a product by SmithKline Biologicals, is a noninfectious recombinant DNA hepatitis B vaccine for immunization against infection caused by all known subtypes of hepatitis B virus. It provides a safe and well-tolerated vaccination regimen shown to confer immunity on the basis of anti-HBs antibody responses comparable with those of plasma-derived vaccines.