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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a single dose of the HPV vaccine (Gardasil-9) provides the same immune protection as two or three doses. HPV (human papillomavirus) can cause several types of cancer, and understanding the vaccine's mechanism can enhance future vaccines. The trial includes healthy adults who have not previously received the HPV vaccine or had certain HPV-related conditions, such as genital warts or abnormal pap tests. Participants will receive either one or two doses of the vaccine, and researchers will collect blood, lymph node, and bone marrow samples to study their immune response. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective vaccine can benefit more patients.

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 is the safety track record for Gardasil-9?

Research shows that Gardasil-9, the HPV vaccine used in this study, is usually well-tolerated. Studies have found that the most common side effects are mild, including pain, swelling, redness, or occasionally a small bump at the injection site. Some individuals might also experience dizziness, headaches, or nausea. Serious side effects are rare. No evidence links the vaccine to long-term health problems like infertility. This safety information comes from data on large numbers of people who have received the vaccine. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments because Gardasil-9 offers a new approach to HPV vaccination. Unlike the standard three-dose schedule, this trial is exploring the effectiveness of just one or two doses of the 9-valent HPV vaccine, potentially making vaccination more accessible and easier for people to complete. The unique feature of Gardasil-9 is its coverage of nine HPV types, which is broader than earlier vaccines, offering the potential for greater protection against cervical and other HPV-related cancers. If successful, these simplified dosing regimens could increase vaccination rates and reduce the burden of HPV-related diseases worldwide.

What is the effectiveness track record for the HPV vaccine?

Research shows that the HPV vaccine, Gardasil-9, effectively prevents cancers caused by HPV. In this trial, participants will receive either one or two doses of the 9-valent HPV vaccine. Studies have found that one dose can prevent 97.5% of the cancer-causing HPV types, suggesting it might work as well as two or three doses. For those receiving two doses in this trial, research indicates the immune response matches that of three doses. Overall, Gardasil-9 has proven to create a strong defense against HPV, offering significant protection against the virus. ^{6 7 8 9 10}

Who Is on the Research Team?

Erin Scherer, PhD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

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

Available and willing to participate for the duration of this study

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

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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]

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]

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]

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]

Citations

1. publichealth.jhu.edu publichealth.jhu.edu/ivac/the-power-of-a-single-dose-evidence-for-a-single-dose-hpv-vaccine-schedule

Evidence for a Single-Dose HPV Vaccine Schedule In a randomized trial in Kenya (KEN SHE), a single-dose of HPV vaccine was found to be 97.5% effective in preventing cancer-causing strains of HPV among 15–20- ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10769028/

The clinical effectiveness of one-dose vaccination with an ... Our analysis suggests that a single-dose HPV vaccine may offer effectiveness on par with two- or three-dose schedules.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0264410X24000586

Evidence for an HPV one-dose schedule Results showed that one dose of the HPV vaccine has comparable efficacy (82.1 %) against HPV 16/18 prevalent infection as three doses of the ...

4. cdc.gov cdc.gov/vaccines/vpd/hpv/hcp/vaccines.html

HPV Vaccine Efficacy More than 98% of recipients develop an antibody response to HPV types included in the respective vaccines 1 month after completing a full vaccination series.

5. merckvaccines.com merckvaccines.com/gardasil9/efficacy/

Efficacy of GARDASIL®9 (Human Papillomavirus 9-valent ... Efficacy and effectiveness of GARDASIL are relevant to GARDASIL 9 since the vaccines are manufactured similarly and contain 4 of the same HPV L1 VLPs.

6. gardasil9.com gardasil9.com/patient-pd/what-is-gardasil-9/safety-and-side-effects/

GARDASIL 9 safety and side effects The most common side effects of GARDASIL 9 include: pain, swelling, redness, itching, bruising, bleeding, and a lump where your child got the shot.

7. cdc.gov cdc.gov/vaccine-safety/vaccines/hpv.html

Human Papillomavirus (HPV) Vaccine Safety The most common side effect reported was pain, swelling, and redness in the arm where the shot was given. · These mild side effects may occur more often after ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12269663/

Adverse events following 9-valent human papillomavirus ... The overwhelming majority of reported events were non-serious in nature, with dizziness, syncope, headache, and various injection site reactions ...

9. gardasil9.com gardasil9.com/patient-a/what-is-gardasil-9/safety-and-side-effects/

Safety Profile and Possible Side Effects of GARDASIL®9 ... The side effects include pain, swelling, redness, itching, bruising, bleeding, and a lump where you got the shot; headache; fever; nausea; and dizziness.

10. cancer.gov cancer.gov/news-events/cancer-currents-blog/2021/hpv-vaccine-parents-safety-concerns

Parent Concerns About HPV Vaccine Safety Increasing - NCI The most common serious side effects of HPV vaccination are dizziness and fainting. There is no evidence that HPV vaccines lead to infertility ...