HPV Vaccine Dosing Schedules for Human Papillomavirus

Overseen By Rosalina M Trujillo

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: The University of Texas Medical Branch, Galveston

Must not be taking: Immunosuppressants, Chemotherapy, Corticosteroids, others

Disqualifiers: Pregnancy, Immunodeficiency, Autoimmune diseases, 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 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

Duration: 6 months

618 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether two doses of the 9-valent HPV vaccine (Gardasil 9) are as effective as the usual three doses in enhancing the body's defenses against HPV (human papillomavirus). Women aged 27 to 45 who have not previously received the HPV vaccine can participate. Participants will be divided into two groups to receive either two or three doses and will provide blood samples over 12 months to monitor their immune response. The trial aims to determine if fewer doses can still offer strong protection, making vaccination more convenient. As a Phase 4 trial, the vaccine has already received FDA approval and proven effective, and this research seeks to understand its benefits for 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, but you cannot participate if you are on treatments that suppress the immune system, like chemotherapy or certain immune-suppressing drugs.

What is the safety track record for the 9-valent HPV vaccine?

Research has shown that the 9-valent HPV vaccine, known as Gardasil 9, is safe and generally well-tolerated. The FDA approved this vaccine in 2014 after it passed strict safety tests. In previous studies, most participants experienced only mild side effects, such as soreness at the injection site, while serious side effects were rare.

Typically, adults receive the vaccine in three doses, but younger individuals may receive two doses. Although less information exists on the duration of protection for adults on the two-dose schedule, current studies are investigating this. The vaccine's strong safety record provides reassurance for those considering participation in trials. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these HPV vaccine dosing schedules because they could simplify and improve HPV vaccination. The trial is comparing the standard three-dose regimen of the 9-valent HPV vaccine to an alternative two-dose schedule. If the two-dose schedule proves effective, it could make HPV vaccination more accessible and encourage higher vaccination rates by reducing the number of clinic visits required. This change has the potential to maintain strong protection against HPV while being more convenient for patients.

What is the effectiveness track record for the 9-valent HPV vaccine?

Research has shown that the 9-valent HPV vaccine is safe and effective, providing protection against nine types of HPV, including those most likely to cause cancer. Over ten years, individuals who received the vaccine experienced lower rates of ongoing HPV infections and related diseases. In this trial, participants will follow different dosing schedules. Studies comparing two-dose and three-dose schedules suggest that two doses are nearly as effective if spaced correctly. If the two doses offer protection for at least 20 years, the additional benefit of a third dose is minimal. This makes the two-dose schedule a promising option to reduce the number of shots needed. ^{2 6 7 8 9}

Who Is on the Research Team?

Abbey B Berenson, MD, PhD

Principal Investigator

University of Texas

Are You a Good Fit for This Trial?

This trial is for females aged 27-45 who haven't had the HPV vaccine, use reliable birth control, and can consent. They must have a way to pay for the vaccine, speak English or Spanish, and have phone access. Pregnant women or those planning pregnancy soon, with suppressed immune systems or certain medical conditions are excluded.

Inclusion Criteria

Identified source of funding for vaccine such as Medicaid, private health insurance, Texas Healthy Women program, etc.

Reports consistent use of reliable birth control and plans to continue its use through study month 13

Ability to give informed consent

Exclusion Criteria

Plans to move out of the Galveston/Houston area in the 13 months following study entry

I have had more than 10 sexual partners in my lifetime.

Currently pregnant or plans to become pregnant or donate eggs in the next 13 months

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either 2 or 3 doses of the 9-valent HPV vaccine over 6 months

6 months

4 visits (in-person) for blood draws and vaccinations

Follow-up

Participants are monitored for immune response through blood samples

12 months

4 visits (in-person) for blood draws

Open-label extension (optional)

Participants in the 2-dose group are offered a 3rd dose after the final blood draw

Post 12-month follow-up

What Are the Treatments Tested in This Trial?

Interventions

• 9-valent HPV vaccine

Trial Overview The study compares two schedules of the HPV vaccine: one group will receive two doses at different times while another gets three doses at standard intervals. The goal is to see if fewer doses still provide strong immunity against HPV over a year.

How Is the Trial Designed?

Group I: Females, 2-dose alternative Experimental Treatment 1 Intervention

Two doses of the 9-valent HPV vaccine to be administered to the experimental group (27-45 years of age) at 0 and 6 months. Additional HPV vaccine dose will be offered after final blood draw at 12 months.

Group II: Females, 3-dose standard Active Control 1 Intervention

Three doses of the 9-valent HPV vaccine to be administered to the comparison group (27-45 years of age) at 0, 2, and 6 months.

9-valent HPV vaccine is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Gardasil 9 for:

• Cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers caused by HPV Types 16, 18, 31, 33, 45, 52, and 58
• Cervical, vulvar, vaginal, and anal precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58
• Genital warts caused by HPV Types 6 and 11

Approved in European Union as Gardasil 9 for:

• Cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers caused by HPV Types 16, 18, 31, 33, 45, 52, and 58
• Cervical, vulvar, vaginal, and anal precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58
• Genital warts caused by HPV Types 6 and 11

Approved in Canada as Gardasil 9 for:

• Cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers caused by HPV Types 16, 18, 31, 33, 45, 52, and 58
• Cervical, vulvar, vaginal, and anal precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58
• Genital warts caused by HPV Types 6 and 11

Approved in Switzerland as Gardasil 9 for:

• Cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers caused by HPV Types 16, 18, 31, 33, 45, 52, and 58
• Cervical, vulvar, vaginal, and anal precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58
• Genital warts caused by HPV Types 6 and 11

Who Is Running the Clinical Trial?

The University of Texas Medical Branch, Galveston

Lead Sponsor

Trials

263

Recruited

55,400+

Cancer Prevention Research Institute of Texas

Collaborator

Trials

55

Recruited

98,900+

Published Research Related to This Trial

The study involving 220 college-age males found that an alternate dosing schedule for the HPV vaccine (0, 2, 12 months) is not only non-inferior but also superior in generating immune responses compared to the standard schedule (0, 2, 6 months).

This flexibility in the dosing schedule could potentially increase vaccination rates among college-age males, addressing the issue of low vaccine uptake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized controlled trial of two dosing schedules for human papillomavirus vaccination among college age males. Lin, CJ., Zimmerman, RK., Nowalk, MP., et al.[2021]

A study involving 371 children aged 9-10 years found that a mixed vaccination schedule using one dose of the nonavalent (9vHPV) and one dose of the bivalent vaccine (2vHPV) was immunogenic, achieving 100% seropositivity for all 9 HPV types included in the 9vHPV vaccine after the second dose.

The mixed vaccination schedule had an acceptable safety profile, although more local or systemic adverse events were reported in subjects who received the 2vHPV as the first dose compared to those who received the 9vHPV first.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of a mixed vaccination schedule with one dose of nonavalent and one dose of bivalent HPV vaccine versus two doses of nonavalent vaccine - A randomized clinical trial. Gilca, V., Sauvageau, C., Panicker, G., et al.[2020]

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 (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) 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 demonstrated a high efficacy of 92.3% in preventing high-grade cervical, vulvar, and vaginal dysplasia related to HPV types 31, 33, 45, 52, and 58 in a study involving 5,312 participants aged 9-26 years.

The vaccine was well tolerated, with over 99% of recipients developing antibodies for all 9 HPV types, and most adverse events were mild to moderate, supporting its use in vaccination programs in Latin America.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, immunogenicity, and safety of a 9-valent human papillomavirus vaccine in Latin American girls, boys, and young women. Ruiz-Sternberg, ÁM., Moreira, ED., Restrepo, JA., et al.[2021]

The 9-valent HPV vaccine (9vHPV) was well tolerated in over 15,000 participants aged 9 to 26, with a safety profile similar to the quadrivalent HPV vaccine, showing mostly mild-to-moderate adverse events like injection-site pain and headaches.

Serious adverse events were very rare (0.1%), and the vaccine did not show any significant safety concerns related to pregnancy outcomes, supporting its widespread use for HPV prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Profile of the 9-Valent HPV Vaccine: A Combined Analysis of 7 Phase III Clinical Trials. Moreira, ED., Block, SL., Ferris, D., et al.[2019]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4978371/

Comparison of 2-Dose and 3-Dose 9-Valent Human ... Our model predicts that if 2 doses of 9-valent vaccine protect for ≥20 years, the additional benefits of a 3-dose schedule are small as compared to those of 2- ...

2. cdc.gov cdc.gov/vaccines/vpd/hpv/hcp/recommendations.html

HPV Vaccination Recommendations The second dose of HPV vaccine should be given 6 to 12 months after the first dose. Adolescents who receive two doses less than 5 months apart will require a ...

3. 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 After 18 months of follow-up, both the bivalent and nonavalent vaccines demonstrated 97.5% vaccine efficacy against high-risk strains of HPV. Researchers ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4865336/

Update on the new 9-valent vaccine for human ... The 9-valent HPV vaccine, which protects against HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58, is safe and effective and will further reduce the incidence ...

5. 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 ...

6. gardasil9.com gardasil9.com/patient-pd/what-is-gardasil-9/gardasil9-schedule/

HPV vaccine schedule For persons 15 through 45 years of age, GARDASIL 9 is given using a 3-dose schedule; the second shot should be given 2 months after the first shot and the third ...

7. gardasil9.com gardasil9.com/patient-a/what-is-gardasil-9/dosing-schedule/

GARDASIL 9 is a 3-shot vaccination series for adults For persons 9 through 14 years of age, GARDASIL 9 can be given using a 2-dose or 3-dose schedule. For the 2-dose schedule, the second shot should be given 6– ...

8. merck.com merck.com/product/usa/pi_circulars/g/gardasil_9/gardasil_9_pi.pdf

gardasil_9_pi.pdf The 9-valent. HPV VLP vaccine is a sterile liquid suspension that is ... Duration of immunity of a 2-dose schedule of GARDASIL 9 has not been established.

9. 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 ...