Heplisav-B for Liver Cirrhosis

Overseen By Paul Thuluvath, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Mercy Medical Center

Disqualifiers: Allergy to vaccine, Hepatitis B exposure, Liver transplant, 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 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

200 Participants Needed

Trial Summary

What is the purpose of this trial?

Investigators want to compare the seroconversion rates between two-dose and three-dose regimens of the hepatitis B vaccine (Heplisav B) among patients with cirrhosis, a randomized prospective study.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the drug Heplisav-B for liver cirrhosis?

Heplisav-B, a hepatitis B vaccine, has shown high effectiveness in creating protective antibodies in various groups, including those with chronic liver disease, with seroprotection rates of 90%-100% in adults. This suggests it could be effective for people with liver cirrhosis, as it helps prevent hepatitis B infections, which can worsen liver conditions. ^{1 2 3 4 5}

Is Heplisav-B generally safe for humans?

Heplisav-B, a hepatitis B vaccine, has shown similar safety profiles to current hepatitis B vaccines in clinical trials, meaning it is generally considered safe for humans. However, like all vaccines, it may cause side effects in some people, and any adverse reactions should be reported to health authorities. ^{1 2 3 4 6}

How is the treatment Heplisav-B unique for liver cirrhosis?

Heplisav-B is unique because it is a two-dose hepatitis B vaccine that uses a novel immunostimulatory adjuvant, which helps boost the body's immune response. This makes it more effective in achieving protection against hepatitis B compared to traditional three-dose vaccines, especially in patients with chronic liver disease. ^{1 2 3 5 7}

Research Team

Paul Thuluvath, MBBS, MD, FRCP

Principal Investigator

Mercy Medical Center

Eligibility Criteria

This trial is for adults over 18 with cirrhosis who visit Mercy Medical Center's hepatology clinic and lack immunity to Hepatitis B. It excludes those allergic to the hepatitis B vaccine or its components, yeast, previous hepatitis B exposure, post liver transplant patients, and anyone under 18.

Inclusion Criteria

I am over 18, have cirrhosis, and lack immunity to Hepatitis B.

Exclusion Criteria

Anyone who has had a serious allergic reaction to a prior dose of the hepatitis B vaccine, a component of the hepatitis B vaccine, or yeast should not receive the hepatitis B vaccine

I have been exposed to hepatitis B before.

I have had a liver transplant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Heplisav-B vaccine in either a 2-dose regimen at 0 and 4 weeks or a 3-dose regimen at 0, 4, and 8 weeks

8 weeks

Follow-up

Participants are monitored for seroconversion rates and safety 12 weeks after completing the vaccination series

12 weeks

Treatment Details

Interventions

• Heplisav-B Injectable Product

Trial Overview The study aims to compare how well two different dosing schedules of Heplisav B (a hepatitis B vaccine) work in patients with cirrhosis. One group will receive a two-dose regimen while another will get three doses to see which provides better protection.

Participant Groups

Group I: Non cirrhosis, 3-dose regimen Experimental Treatment 1 Intervention

Investigators will randomize the patient in the noncirrhotic group to receive a 3-dose regimen of Heplisav-B.

Group II: Cirrhosis, 3-dose regimen Experimental Treatment 1 Intervention

Investigators will randomize the patient in the cirrhotic group to receive a 3-dose regimen of Heplisav-B.

Group III: Cirrhosis, 2-dose regimen Active Control 1 Intervention

Investigators will randomize the patient in the cirrhotic group to receive a 2-dose regimen of Heplisav-B.

Group IV: Non cirrhosis, 2-dose regimen Active Control 1 Intervention

Investigators will randomize the patient in the noncirrhotic group to receive a 2-dose regimen of Heplisav-B.

Heplisav-B Injectable Product is already approved in United States for the following indications:

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

Who Is Running the Clinical Trial?

Mercy Medical Center

Lead Sponsor

Trials

22

Recruited

4,400+

Findings from Research

In a study of 32 patients with end-stage renal disease (ESRD) on hemodialysis, 83% of those who completed the 3-dose regimen of the Heplisav-B vaccine successfully developed immunity against hepatitis B virus, indicating its efficacy in this immunocompromised population.

The Heplisav-B vaccine demonstrated a high seroconversion rate with fewer doses compared to standard hepatitis B vaccination regimens, suggesting it could be a more efficient option for patients with ESRD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seroconversion following Heplisav-B, hepatitis B vaccine (recombinant), adjuvanted, in patients with end-stage renal disease at an urban safety net hospital. Walsh, C., McDaniel, K., Lindsey, L., et al.[2023]

In a study of 120 patients with chronic liver disease (CLD), the Heplisav-B vaccine demonstrated a 67.5% efficacy in generating active immunity against hepatitis B, which is significantly higher than the 33-45% efficacy reported for the standard Engerix-B vaccine.

Patients over 50 years old had reduced odds of successful vaccination, indicating that age may impact the effectiveness of Heplisav-B in this population, highlighting the need for further research in older patients and those with advanced liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of a two-dose hepatitis B vaccination with a novel immunostimulatory sequence adjuvant (Heplisav-B) on patients with chronic liver disease: a retrospective study. Kwon, JY., Daoud, N., Ghoz, H., et al.[2023]

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]

HEPLISAV™, a novel hepatitis B vaccine, has shown to induce strong immune responses with fewer doses compared to traditional vaccines, making it particularly beneficial for populations that struggle to achieve adequate immunity.

In Phase III clinical trials, HEPLISAV™ demonstrated a similar safety profile to existing HBV vaccines while effectively providing seroprotective antibody levels, addressing the issue of non-responsiveness in 5-10% of healthy individuals and many immunocompromised patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential of 1018 ISS adjuvant in hepatitis B vaccines: HEPLISAV™ review. Eng, NF., Bhardwaj, N., Mulligan, R., et al.[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]

The recombinant hepatitis B vaccine is generally considered safe and effective in preventing hepatitis B infection, which is a major cause of liver disease worldwide, but it may contain components that could be linked to autoimmune diseases in susceptible individuals.

Despite the potential risks, the overall benefits of the hepatitis B vaccine outweigh its risks, and it is important for patients and physicians to discuss these factors when considering vaccination, while also encouraging reporting of any adverse reactions for further research and safety improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of hepatitis B vaccination. Geier, MR., Geier, DA., Zahalsky, AC.[2019]

In a study of 166 patients with chronic liver disease, the two-dose hepatitis B vaccine (Heplisav-B) achieved a higher seroconversion rate (63%) compared to the three-dose vaccine (Engerix-B) which had a 45% rate, indicating better efficacy for Heplisav-B.

Factors such as cirrhosis, COPD, and renal failure were found to significantly reduce the likelihood of achieving immunity, highlighting the importance of patient health status in vaccine effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-Dose Hepatitis B Vaccine (Heplisav-B) Results in Better Seroconversion Than Three-Dose Vaccine (Engerix-B) in Chronic Liver Disease. Amjad, W., Alukal, J., Zhang, T., et al.[2021]

References

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

Seroconversion following Heplisav-B, hepatitis B vaccine (recombinant), adjuvanted, in patients with end-stage renal disease at an urban safety net hospital. [2023]

2. China pubmed.ncbi.nlm.nih.gov

Efficacy of a two-dose hepatitis B vaccination with a novel immunostimulatory sequence adjuvant (Heplisav-B) on patients with chronic liver disease: a retrospective study. [2023]

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

The potential of 1018 ISS adjuvant in hepatitis B vaccines: HEPLISAV™ review. [2021]

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. England pubmed.ncbi.nlm.nih.gov

A review of hepatitis B vaccination. [2019]

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

Two-Dose Hepatitis B Vaccine (Heplisav-B) Results in Better Seroconversion Than Three-Dose Vaccine (Engerix-B) in Chronic Liver Disease. [2021]