HPV Vaccine for Human Papillomavirus

Overseen By Erin Scherer, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Emory University

Must not be taking: Anticoagulants, NSAIDs, Immunosuppressants, others

Disqualifiers: HPV history, Severe comorbidities, Immunosuppression, 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

Compensation: Varies

Number of Visits: 1

Duration: 6 months

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This study aims to answer the question: does 1-dose HPV vaccination generate the same immune responses compared to 2- or 3-dose HPV vaccination? This will be done by studying the immune response in blood, lymph nodes, and bone marrow. Human papillomaviruses (HPV) cause cancers (cervical, anal, oropharyngeal, vulvar, vaginal, and penile), and the current HPV vaccine is highly effective at preventing disease by HPV types that cause 90% of cancer cases. While this vaccine generates high levels of antibodies that last for \> 10 years, understanding of how this occurs is limited, and studying this immune response will help design new and better vaccines. The study population consists of healthy adult (age 18-45) participants who have not previously received an HPV vaccine, do not have antibodies against certain types of HPV, do not have a history of HPV infection or disease (such as genital warts, abnormal pap test, or HPV DNA test), and do not have contraindications to study procedures. Populations of increased concern are not being enrolled.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are taking blood thinners, anti-platelet products, or NSAIDs (like aspirin), you may need to stop these at least a week before participating. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug Gardasil-9 for HPV?

Gardasil-9 is shown to be effective in preventing infections from nine types of HPV, which are linked to about 90% of cervical cancer cases. Clinical trials have demonstrated that it produces strong immune responses in young women and is safe, with similar effectiveness in younger boys and girls. ^{1 2 3 4 5}

Is the HPV vaccine, including Gardasil-9, generally safe for humans?

The HPV vaccine, including Gardasil-9, is generally considered safe with a low rate of serious adverse events. Most reported side effects are mild, and serious reactions are rare, occurring in less than 1 in 100,000 doses. ^{6 7 8 9 10}

How is Gardasil-9 different from other HPV vaccines?

Gardasil-9 is unique because it protects against nine types of HPV, including five additional high-risk types not covered by earlier vaccines, increasing protection from about 70% to 90% against cervical cancer. This expanded coverage makes it a more comprehensive option for preventing HPV-related diseases. ^{3 4 7 11 12}

Research Team

Erin Scherer, PhD

Principal Investigator

Emory University

Eligibility Criteria

This trial is for healthy adults aged 18-45 who haven't had the HPV vaccine or past HPV infections. Participants should not have antibodies against certain HPV types, a history of genital warts, abnormal pap tests, or positive HPV DNA tests. They must also be able to undergo study procedures without contraindications.

Inclusion Criteria

I am willing to delay finishing my 9vHPV vaccine series.

In good health based on physical examination, vital signs, medical history, and the investigator's clinical judgment

Available and willing to participate for the duration of this study

Exclusion Criteria

I have not received blood products or immunoglobulin in the last 3 months.

I have received an HPV vaccine dose.

I am currently immunosuppressed due to cancer treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

8 weeks

1 visit (in-person)

Treatment

Participants receive 1 or 2 doses of the 9-valent HPV vaccine

6 months

Multiple visits for blood draws and lymph node sampling

Follow-up

Participants are monitored for immune response and safety, including bone marrow sampling

5 years

Regular visits for blood draws and bone marrow sampling

Treatment Details

Interventions

• Gardasil-9

Trial Overview The study compares immune responses in individuals given one dose of the Gardasil-9 vaccine versus those receiving two or three doses. It will measure antibody levels in blood, lymph nodes, and bone marrow to assess if a single dose can provide similar protection.

Participant Groups

Group I: One dose of the 9-valent HPV vaccine Experimental Treatment 3 Interventions

Participants will receive one dose of the 9-valent HPV (9vHPV) vaccine by intramuscular injection on Day 0. Participants will be asked to donate blood samples for immunologic testing at screening (from Day -60 to -1), on Day 0 (before vaccination), 7±1, 30±5, 180±5 (before vaccination; Visit 5), Visit 5 + 7±1 days, Visit 5 + 30±5 days, 365±14, 730±14, 1095±14, 1460±14, 1825±30 (Visit 15), and ≥84 days from Visit 15 (Optional Visit 17). Axillary lymph node sampling by fine needle aspiration (FNA) will be done 3 times per group on Day 30±5, 180±5 (Visit 5), Visit 5 + 30±5 days. Bone marrow sampling will be done for all groups at Days 730±14 and 1825±30.

Group II: Two doses of the 9-valent HPV vaccine Active Control 3 Interventions

Participants will receive two doses of the 9vHPV vaccine on Day 0 and a second dose 6 months later. Participants will be asked to donate blood samples for immunologic testing at screening (from Day -60 to -1), on Day 0 (before vaccination), 7±1, 30±5, 180±5 (before vaccination; Visit 5), Visit 5 + 7±1 days, Visit 5 + 30±5 days, 365±14, 730±14, 1095±14, 1460±14, 1825±30 (Visit 15), and ≥84 days from Visit 15 (Optional Visit 17). Axillary lymph node sampling by fine needle aspiration (FNA) will be done 3 times per group on Day 30±5, 180±5 (Visit 5), Visit 5 + 30±5 days. Bone marrow sampling will be done for all groups at Days 730±14 and 1825±30.

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

All three HPV vaccines (bivalent, quadrivalent, and 9vHPV) show high efficacy in preventing infections from specific HPV types and associated high-grade cervical dysplasia in women who have not been previously exposed to HPV.

While the bivalent and quadrivalent vaccines have demonstrated early clinical effectiveness in reducing HPV 16 and 18 prevalence, the overall benefits of HPV vaccination in reducing cervical cancer are still largely theoretical, highlighting the need for large-scale studies to confirm long-term effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of 2-, 4- and 9-valent HPV vaccines on morbidity and mortality from cervical cancer. Luckett, R., Feldman, S.[2018]

The nine-valent HPV vaccine, Gardasil9, significantly increases the efficacy against cervical cancer from 70% to 90% compared to the quadrivalent vaccine, covering a broader range of HPV types.

Gardasil9 also provides high efficacy (97%) against lesions associated with HPV types 31, 33, 45, 52, and 58, while maintaining similar effectiveness against HPV types 6, 11, 16, and 18 as the quadrivalent vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nine-valent HPV vaccine - new generation of HPV vaccine]. Fait, T., Dvořák, V., Pilka, R.[2018]

The 9-valent HPV vaccine (Gardasil 9®) significantly increases protection against cervical cancer by covering 9 oncogenic HPV types, raising potential protection from about 70% to 90%, based on clinical trials involving young women.

Clinical trials demonstrated that the 9vHPV vaccine has a comparable safety profile and immunogenicity to the original 4-valent vaccine, with a 2-dose regimen showing similar effectiveness in younger boys and girls compared to the standard 3-dose regimen for older women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanded strain coverage for a highly successful public health tool: Prophylactic 9-valent human papillomavirus vaccine. Zhang, Z., Zhang, J., Xia, N., et al.[2019]

While clinical trials have shown that HPV vaccines are highly effective, their effectiveness in the general population is still not fully understood, highlighting the need for further research.

A comprehensive review of HPV-related clinical outcomes suggests that tracking these outcomes at the population level is crucial for evaluating the real-world effectiveness of HPV vaccines, as many large trials are nearing completion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the impact of human papillomavirus vaccines. Chang, Y., Brewer, NT., Rinas, AC., et al.[2009]

A comprehensive analysis of adverse events (AEs) reported to the Vaccine Adverse Event Reporting System (VAERS) identified 3,112 AEs for Cervarix, 31,606 for Gardasil, and 6,872 for Gardasil 9, highlighting the need for ongoing monitoring of vaccine safety.

The study found 46 unique serious adverse events (SAEs) associated with the HPV vaccines, clustered around behavioral, neurological, immune, nervous, and reproductive systems, indicating that while the vaccines are effective, further research is needed to understand the cause-and-effect relationships of these AEs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OAE-based data mining and modeling analysis of adverse events associated with three licensed HPV vaccines. Zi, W., Yang, Q., Su, J., et al.[2022]

A study involving 215,965 individuals who received the nine-valent HPV vaccine (HPV9) found no new safety concerns, confirming its established safety profile from previous research.

While some elevated event categories were noted, such as skin disorders and ill-defined conditions, most were either previously known or had other causes, and no deaths were linked to the vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of 9-valent human papillomavirus vaccine administered to males and females in routine use. Hansen, J., Yee, A., Lewis, N., et al.[2023]

In a study of 266,647 doses of Gardasil-9® administered in Puglia, Italy, only 22 adverse events following immunization (AEFIs) were reported, resulting in a low reporting rate of 8.25 per 100,000 doses, indicating a favorable safety profile for the vaccine.

Out of the 22 reported AEFIs, only 5 were classified as serious, with 2 leading to hospitalization; however, only 2 serious AEFIs were consistently associated with the vaccine, suggesting that the benefits of Gardasil-9® outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-Life Safety Profile of the 9-Valent HPV Vaccine Based on Data from the Puglia Region of Southern Italy. Di Lorenzo, A., Berardi, P., Martinelli, A., et al.[2022]

In a study involving 12,066 women aged 9 to 26 years who received the HPV vaccines Gardasil® and Cervarix® over three years, 61% reported experiencing mild and transient adverse events after the first dose.

The high rate of reported adverse events is attributed to the study's design, which encouraged participants to document all occurrences, highlighting the importance of ongoing surveillance for vaccine safety, especially for newly marketed vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Human papillomavirus vaccine register]. Spila-Alegiani, S., Da Cas, R., Giambi, C., et al.[2013]

The post-licensure safety profile of HPV vaccines Gardasil and Cervarix was evaluated using data from three sources, including VigiBase and VAERS, confirming that the reported adverse events align with existing safety data.

The analysis showed that the safety profiles of both vaccines are consistent with the information provided in their Summary of Product Characteristics (SPC), indicating that they are safe for public use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postlicensure safety evaluation of human papilloma virus vaccines. Labadie, J.[2015]

The introduction of the quadrivalent vaccine Gardasil and the bivalent vaccine Cervarix has significantly advanced the prevention of HPV-related diseases, including various cancers and benign conditions like genital warts.

A new multivalent vaccine, Gardasil 9, has been approved and shows promise in providing broader protection against nine HPV subtypes, with ongoing efforts to improve vaccine accessibility and reduce production costs, especially in developing countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second-generation prophylactic HPV vaccines: current options and future strategies for vaccines development. Fruscalzo, A., Londero, AP., Bertozzi, S., et al.[2016]

The 9-valent HPV vaccine (9vHPV) is as effective as the quadrivalent HPV vaccine (qHPV) in generating immune responses against HPV types 6, 11, 16, and 18, while also providing a 96.7% risk reduction against high-grade cervical, vulvar, or vaginal diseases related to five additional HPV types in females aged 16-26.

The 9vHPV vaccine has been shown to be safe and well tolerated, with evidence supporting its efficacy in both males and females aged 9-26, indicating its potential to significantly expand protection against HPV infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human papillomavirus 9-valent vaccine for cancer prevention: a systematic review of the available evidence. Signorelli, C., Odone, A., Ciorba, V., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

HPV Vaccination after Primary Treatment of HPV-Related Disease across Different Organ Sites: A Multidisciplinary Comprehensive Review and Meta-Analysis. [2022]

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

Impact of 2-, 4- and 9-valent HPV vaccines on morbidity and mortality from cervical cancer. [2018]

3. Czech Republic pubmed.ncbi.nlm.nih.gov

[Nine-valent HPV vaccine - new generation of HPV vaccine]. [2018]

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

Expanded strain coverage for a highly successful public health tool: Prophylactic 9-valent human papillomavirus vaccine. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Evaluating the impact of human papillomavirus vaccines. [2009]

6. England pubmed.ncbi.nlm.nih.gov

OAE-based data mining and modeling analysis of adverse events associated with three licensed HPV vaccines. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Safety of 9-valent human papillomavirus vaccine administered to males and females in routine use. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Real-Life Safety Profile of the 9-Valent HPV Vaccine Based on Data from the Puglia Region of Southern Italy. [2022]

9. Italy pubmed.ncbi.nlm.nih.gov

[Human papillomavirus vaccine register]. [2013]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Postlicensure safety evaluation of human papilloma virus vaccines. [2015]

11. Italy pubmed.ncbi.nlm.nih.gov

Second-generation prophylactic HPV vaccines: current options and future strategies for vaccines development. [2016]

12. England pubmed.ncbi.nlm.nih.gov

Human papillomavirus 9-valent vaccine for cancer prevention: a systematic review of the available evidence. [2022]