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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a hepatitis B vaccine called Heplisav-B to evaluate its effectiveness in people with liver cirrhosis. Researchers aim to determine if two doses are as effective as three doses in building immunity. Individuals diagnosed with liver cirrhosis who have not developed immunity to hepatitis B are suitable candidates for this trial. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and effective treatment benefits a broader range of patients.

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 is the safety track record for Heplisav-B?

Previous studies have shown that HEPLISAV-B is well-tolerated in adults. Most recipients reported only mild side effects, such as soreness at the injection site and fatigue, while serious side effects were rare.

The FDA has already approved HEPLISAV-B for preventing hepatitis B in adults, indicating a strong safety record. However, its safety and effectiveness in adults undergoing hemodialysis (a kidney treatment) have not been established.

Overall, the vaccine is considered safe, but discussing any concerns with a healthcare provider is always important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for liver cirrhosis focus on managing symptoms and complications, but Heplisav-B offers a different approach. Researchers are excited about Heplisav-B because it is a hepatitis B vaccine, which could potentially prevent future liver damage in patients with cirrhosis by boosting their immune response against the hepatitis B virus. Unlike standard treatments, which generally do not address the underlying causes of liver damage, Heplisav-B might help protect the liver from viral attacks. Additionally, the vaccine's different dosing regimens—2-dose and 3-dose—provide flexibility and could improve patient compliance and outcomes.

What evidence suggests that Heplisav-B could be an effective treatment for cirrhosis?

Research has shown that Heplisav-B effectively protects against hepatitis B. One study found that 95% of adults were protected after receiving two doses in just one month. For individuals with chronic liver disease, Heplisav-B was 67.5% effective, outperforming the 33-45% effectiveness reported for another vaccine, Engerix-B. The vaccine provides rapid protection with just two doses. This trial will evaluate Heplisav-B in different dosing regimens for participants with and without cirrhosis, making it a strong choice for preventing hepatitis B, especially in adults with liver conditions like cirrhosis. ^{6 7 8 9 10}

Who Is on the Research Team?

Paul Thuluvath, MBBS, MD, FRCP

Principal Investigator

Mercy Medical Center

Are You a Good Fit for This Trial?

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.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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]

Citations

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

Study Results - HEPLISAV-B® (Recombinant), Adjuvanted In a pivotal study of adults aged 18–55, 95% of those who received HEPLISAV‑B were protected after only 2 doses in 1 month, in a head-to-head study vs Engerix‑ ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9813651/

Efficacy of a two-dose hepatitis B vaccination with a novel ... In patients with CLD, Heplisav-B's overall efficacy (67.5%) is greater than reports of Engerix-B (33–45%), and thus is an effective hepatitis B ...

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

Dosing Efficiency - HEPLISAV-B® (Recombinant), Adjuvanted HEPLISAV-B provides faster protection with 2-dose completion in 1 month. 1 Series completion is critical to help ensure protective immunity.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0264410X2100582X

Comparative cost-effectiveness of a 2-dose versus 3 ... Overall, HEPLISAV-B was cost-effective in multiple adult populations recommended for HBV vaccination in the United States.

5. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT04588077?draw=2&rank=1

NCT04588077 | Comparison Between 2-dose Versus 3- ... Comparison the Seroconversion Rate Between Two-dose and Three-dose Regimens of Heplisav B Among Patients With Cirrhosis, a Randomized-control Prospective Study.

6. 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.

7. fda.gov fda.gov/media/108745/download

Package Insert - HEPLISAV-B Safety and effectiveness of HEPLISAV-B have not been established in adults on hemodialysis. HEPLISAV-B [Hepatitis B Vaccine (Recombinant), Adjuvanted] is an ...

8. heplisavbhcp.com heplisavbhcp.com/heplisav-b-safety-profile/

Safety Profile - HEPLISAV-B® (Recombinant), Adjuvanted See the HEPLISAV-B® safety profile and learn about a hepatitis B vaccine option for your patients. See the benefits of HEPLISAV-B® dosing and hep B protection.

9. hhs.texas.gov hhs.texas.gov/sites/default/files/documents/doing-business-with-hhs/provider-portal/facilities-regulation/psychiatric/monograph/hepatitis-b-vaccine-recombinant-heplisav-b-monograph.pdf

Hepatitis B Vaccine Recombinant, Adjuvant (HEPLISAV-B) 6. Safety and efficacy of Heplisav-B have not been established in adults on hemodialysis. 6. Adverse Effects: The most common adverse effects of Heplisav-B in ...

10. heplisavbhcp.com heplisavbhcp.com/

HEPLISAV-B® (Recombinant), Adjuvanted - Hepatitis B ... HEPLISAV‑B does not treat liver diseases such as cirrhosis or liver cancer. ... Available data, primarily in individuals who received one dose of HEPLISAV‑B in ...