HPV Vaccine Regimens for Human Papillomavirus

Not currently recruiting at 34 trial locations

Overseen By Toll Free Number

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Immunosuppressants, Immunoglobulins

Disqualifiers: Allergy, Immunocompromised, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests different HPV vaccine schedules to determine if fewer doses can be as effective as the standard three-dose regimen. It aims to prevent human papillomavirus (HPV), a virus linked to certain cancers. The study includes multiple groups: boys and girls aged 9 to 14 and young women aged 16 to 26. Participants may qualify if they have had no sexual activity for the younger groups or limited sexual partners for the older group. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants an opportunity to contribute to potentially groundbreaking advancements in HPV prevention.

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 currently receiving immunosuppressive therapies or have received them in the last year, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the 9-valent human papillomavirus (9vHPV) vaccine, known as Gardasil 9, is generally well-tolerated. The FDA approved this vaccine in 2014, indicating it passed strict safety tests. Studies have found that the vaccine is safe across different dosing schedules.

For example, research on two-dose schedules, with doses given 12 to 53 months apart, has shown that these schedules maintain strong antibody levels without raising safety concerns. Adolescents who received two doses 12 to 53 months apart demonstrated strong immune responses and did not experience significant safety issues.

Moreover, long-term safety data over many years supports the vaccine's safety. It is not associated with serious health problems and offers protection for at least 12 years after just one dose. These findings suggest the vaccine is generally safe for the age groups and dosing schedules in this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the different HPV vaccine regimens because they aim to simplify and potentially enhance the effectiveness of HPV vaccination schedules. Unlike the standard three-dose regimen, these new approaches explore fewer doses given over varied timeframes, which could make it easier for more people to complete the vaccination series. By testing dosages spaced over months to years, the study seeks to determine if long-term protection can be achieved with fewer doses, making it more accessible and increasing vaccination rates. Additionally, a successful outcome could mean stronger, longer-lasting immunity against HPV-related cancers with less frequent doctor visits.

What evidence suggests that this trial's HPV vaccine regimens could be effective?

Research has shown that the 9-valent HPV (9vHPV) vaccine effectively prevents HPV infections. Studies indicate that over 98% of individuals develop a protective response to the HPV types covered by the vaccine after completing the full series of shots. In this trial, participants will receive different dosing regimens of the 9vHPV vaccine. For young women aged 16–26, who are part of one of the study cohorts, the vaccine demonstrated 96.7% effectiveness in preventing infections. Additionally, protection from the 9vHPV vaccine lasts for at least 10 years. These findings suggest that the vaccine is highly effective in preventing HPV-related infections and diseases. ^{2 6 7 8 9}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for boys and girls aged 9-14, and young women aged 16-26 with a history of limited sexual partners. Participants should not be sexually active during the study or plan to become so. Women must have normal Pap tests. Those previously vaccinated with one dose of HPV vaccine can join, but those who are pregnant, immunocompromised, or have severe allergies cannot.

Inclusion Criteria

I received one HPV vaccine dose over a year ago and no others.

I received one dose of the 9vHPV vaccine over a year ago and no other HPV vaccines since.

I am a woman aged 16-26, never had or only had normal Pap tests, and have had up to 4 sexual partners.

Exclusion Criteria

History of severe allergic reaction that required medical intervention

Known allergy to any vaccine component

Currently immunocompromised, or been diagnosed with immunodeficiency

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vaccination

Participants receive the 9vHPV vaccine according to their assigned cohort regimen

Up to 60 months

Multiple visits depending on cohort schedule

Follow-up

Participants are monitored for safety and immunogenicity, including antibody titers and adverse events

36 months post last vaccination

Long-term Follow-up

Participants are monitored for serious vaccine-related adverse events throughout the study period

Up to 96 months

What Are the Treatments Tested in This Trial?

Interventions

• 9vHPV vaccine

Trial Overview The study is testing extended two-dose regimens (0,12; 0,24; 0,36; and 0,60 months) of the 9vHPV vaccine in younger participants against the standard three-dose regimen given to young women at intervals of 0,2,and6 months. The aim is to compare safety and immune response over a period of up to eight years.

How Is the Trial Designed?

Group I: Cohort 4: 2 Doses of 9vHPV Vaccine Given 60 Months Apart Experimental Treatment 1 Intervention

9 to 10 year old girls and boys receive a 2-dose regimen of 9vHPV vaccine at Day 1 and Month 60.

Group II: Cohort 3: 2 Doses of 9vHPV Vaccine Given 36 Months Apart Experimental Treatment 1 Intervention

9 to 12 year old girls and boys receive a 2-dose regimen of 9vHPV vaccine at Day 1 and Month 36.

Group III: Cohort 2: 2 Doses of 9vHPV Vaccine Given 24 Months Apart Experimental Treatment 1 Intervention

9 to 13 year old girls and boys receive a 2-dose regimen of 9vHPV vaccine at Day 1 and Months 24.

Group IV: Cohort 1: 2 Doses of 9vHPV Vaccine Given 12 Months Apart Experimental Treatment 1 Intervention

9 to 14 year old girls and boys receive a 2-dose regimen of 9vHPV vaccine at Day 1 and Month 12.

Group V: Cohort 0: 1 Dose of 9vHPV Vaccine (previous 1-dose recipients) Experimental Treatment 1 Intervention

10 to 15 year old girls and boys (who previously received 1 dose of 9vHPV vaccine) receive a second dose of 9vHPV vaccine at Day 1.

Group VI: Cohort 5: 3 Doses of 9vHPV Vaccine Given Over a 6-Month Period Active Control 1 Intervention

16 to 26 year old young women receive 3 dose regimen of 9vHPV vaccine at Day 1, Month 2 and Month 6.

Who Is Running the Clinical Trial?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

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

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

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

Merck Sharp & Dohme LLC

Lead 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

The 9-valent HPV vaccine (9vHPV) is safe and highly effective, showing over 99.8% seroconversion rates for all vaccine types in both groups of a study involving 1054 participants aged 11-15 years.

Administering the 9vHPV vaccine alongside the REPEVAX vaccine did not interfere with the immune response to either vaccine, indicating that this approach can safely reduce the number of vaccination visits needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open-label, randomized study of a 9-valent human papillomavirus vaccine given concomitantly with diphtheria, tetanus, pertussis and poliomyelitis vaccines to healthy adolescents 11-15 years of age. Kosalaraksa, P., Mehlsen, J., Vesikari, T., et al.[2015]

A total of 7244 adverse event reports were received after the 9-valent HPV vaccine (9vHPV) was administered, with 97.4% of these reports classified as nonserious, indicating a favorable safety profile.

No new safety concerns were identified, and the adverse events reported were consistent with those observed in prelicensure trials, confirming that the 9vHPV vaccine is safe for use in the approved age group of 9 to 26 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of the 9-Valent Human Papillomavirus Vaccine. Shimabukuro, TT., Su, JR., Marquez, PL., et al.[2023]

The 9-valent HPV vaccine (9vHPV) is highly immunogenic in females aged 12-26 who previously received the quadrivalent HPV vaccine (qHPV), with over 98% showing seropositivity for additional HPV types 31/33/45/52/58 after the third dose.

While injection-site adverse events were more common in the 9vHPV group (91.1%) compared to placebo (43.9%), systemic adverse events were similar between both groups, indicating that the 9vHPV vaccine is generally well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of a 9-valent HPV vaccine in females 12-26 years of age who previously received the quadrivalent HPV vaccine. Garland, SM., Cheung, TH., McNeill, 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 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 9-valent HPV vaccine (9vHPV) has been shown to be generally well tolerated in both prior recipients of the quadrivalent HPV vaccine and young men, with a low incidence of serious adverse events (AEs).

The most common AEs were mild injection-site reactions, occurring in over 90% of prior qHPV vaccine recipients and 79% of young men, indicating that the vaccine is safe for use in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of the 9-valent human papillomavirus vaccine: assessment in prior quadrivalent HPV vaccine recipients and in men 16 to 26 years of age. Moreira, ED., Giuliano, AR., de Hoon, J., et al.[2019]

The nonavalent HPV vaccine (9vHPV) has shown increased efficacy compared to the quadrivalent HPV vaccine (4vHPV), with an estimated 90% prevention rate for cervical cancer and up to 80% for precancerous cervical lesions in women aged 16-26 years.

The 9vHPV vaccine may provide broader protection against various HPV-related diseases in both males and females, but its future adoption will depend on factors like cost-effectiveness and ongoing safety monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of the benefits and potential issues of the nonavalent HPV vaccine. Mariani, L., Preti, M., Cristoforoni, P., et al.[2017]

Citations

1. 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.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5974698/

Human papillomavirus 9-valent vaccine for cancer prevention The 9vHPV clinical efficacy has been directly assessed on females aged 16–26 years in one study that reported 96·7% 9vHPV vaccine efficacy against composite ...

3. publications.aap.org publications.aap.org/pediatrics/article/152/4/e2022060993/193886/Ten-Year-Follow-up-of-9-Valent-Human

Ten-Year Follow-up of 9-Valent Human Papillomavirus ... Immunogenicity, effectiveness, and safety were demonstrated through 10 years postvaccination. Rates of persistent infection and disease related ...

4. tandfonline.com tandfonline.com/doi/full/10.1080/21645515.2024.2377903

Long-term effectiveness of the nine-valent human ... Statistically significant protection was provided by the 9vHPV vaccine through at least 10 years, with complete, although not statistically ...

5. 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- ...

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

Human Papillomavirus (HPV) Vaccine Safety Gardasil 9 (human papillomavirus 9-valent vaccine, recombinant; 9vHPV) was approved by FDA for use in 2014. The safety of Gardasil 9 was studied in clinical ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10760320/

Post-marketing safety surveillance study of a 9-valent human ... There were 1000 individuals received at least one dose of 9vHPV vaccine: 982 received three doses and 992 received two doses. And all 982 ...

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

Evidence for an HPV one-dose schedule The currently available data have shown that a single dose of HPV vaccine can provide protection for at least 12 years post-vaccination. The ...

9. hpvroundtable.org hpvroundtable.org/wp-content/uploads/2024/10/Epidemiologic-Evidence-Effectiveness-and-Safety-of-the-HPV-Vaccine.pdf

Epidemiologic-Evidence-Effectiveness-and-Safety-of-the- ... A 2022 study demonstrated that the 9vHPV vaccine is safe over long periods of time and is not linked to severe health events.9. º The research built on the work ...