HPV Vaccine Regimens for Human Papillomavirus

Recruiting at 29 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

700 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a 96-month safety and immunogenicity study conducted in boys and girls 9 to 14 years of age and in young women 16 to 26 years of age. From this study, the goal is to establish that the investigational extended 2-dose regimens (0, 12 months; 0, 24 months; 0, 36 months; and 0, 60 months) studied in boys and girls 9 to 14 years of age are generally safe and immunogenic, with an antibody response that is not inferior to that observed in young women 16 to 26 years of age who receive the standard 3-dose regimen of 9-valent human papillomavirus (9vHPV) vaccine at 0, 2, and 6 months (i.e., the population and dose regimen used to establish 9vHPV vaccine efficacy).

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.

What data supports the effectiveness of the 9vHPV vaccine treatment for preventing HPV-related diseases?

The 9vHPV vaccine has been shown to be highly effective, reducing the risk of high-grade cervical, vulvar, or vaginal diseases by 96.7% in females aged 16-26 years. It also offers expanded protection against additional high-risk HPV types, potentially increasing overall prevention rates for cervical cancer to 90%. ^{1 2 3 4 5}

Is the 9-valent HPV vaccine safe for humans?

The 9-valent HPV vaccine (9vHPV) has been generally well tolerated in clinical trials, with most side effects being mild, such as reactions at the injection site. Serious adverse events were rare and not judged to be vaccine-related, although some studies noted a slightly higher rate of serious events compared to other vaccines. ^{1 2 6 7 8}

How is the 9vHPV vaccine different from other HPV vaccines?

The 9vHPV vaccine is unique because it protects against nine types of HPV, including five additional types (31, 33, 45, 52, and 58) not covered by the earlier quadrivalent HPV vaccine. This broader protection makes it more effective in preventing HPV-related infections and diseases. ^{1 5 7 8 9}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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) 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 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]

References

1. Netherlands 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. [2016]

2. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

Overview of the benefits and potential issues of the nonavalent HPV vaccine. [2017]

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

Safety of the 9-Valent Human Papillomavirus Vaccine. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Serious adverse events after HPV vaccination: a critical review of randomized trials and post-marketing case series. [2022]

7. United States 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. [2019]

8. United States 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. [2015]

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

Phase II studies to select the formulation of a multivalent HPV L1 virus-like particle (VLP) vaccine. [2018]