HPV Vaccine Dosing Schedules for HPV Prevention

Overseen By Rosalina M Trujillo

Age: < 65

Sex: Any

Trial Phase: Phase 4

Sponsor: The University of Texas Medical Branch, Galveston

Must not be taking: Immunosuppressants, Corticosteroids, Monoclonal antibodies, others

Disqualifiers: Pregnancy, Immunodeficiencies, Autoimmune disorders, 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: 7

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether young males and females aged 15-26 need a third dose of the HPV vaccine or if two doses provide equal protection against nine types of HPV (human papillomavirus). Participants will be divided into groups receiving either two doses with an optional third dose later or the usual three doses. The trial seeks individuals who haven't received any HPV vaccine doses and can access the vaccine through specific programs or insurance. As a Phase 4 trial, the HPV vaccine is already FDA-approved and proven effective, and this research aims to understand how it benefits more patients.

Will I have to stop taking my current medications?

If you are currently taking medications that suppress immune function, you may need to stop them to participate in this trial. The protocol does not specify a washout period, but these medications are listed as exclusion criteria.

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

Research has shown that the 9-valent HPV vaccine is generally safe and well-tolerated. Most participants in previous studies experienced only mild side effects, such as soreness at the injection site, headaches, or a mild fever. Serious reactions are rare.

The FDA has approved the vaccine for protection against nine types of HPV, indicating it has undergone thorough testing for safety and effectiveness. Studies also indicate that both the 2-dose and 3-dose schedules are similarly safe.

In summary, the 9-valent HPV vaccine has a strong safety record, making it a reliable choice for preventing diseases related to HPV. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about exploring different dosing schedules for the 9-valent HPV vaccine because they might offer more flexibility and potentially improve vaccine uptake. Unlike the standard three-dose regimen given over six months, the experimental approach involves two doses with a delayed third dose, which could simplify the vaccination process. This alternative schedule might be particularly appealing for those who find it challenging to complete the traditional series, potentially leading to better prevention rates against HPV. By investigating these new schedules, researchers hope to enhance accessibility and effectiveness of HPV prevention strategies.

What evidence suggests that this trial's dosing schedules could be effective for HPV prevention?

Research has shown that the 9-valent HPV vaccine provides strong protection against infections caused by the HPV virus. In this trial, some participants will receive two doses of the vaccine with a delayed third dose, while others will follow a standard three-dose schedule. Studies have found that even with just two doses, the vaccine is nearly 100% effective in preventing long-lasting HPV infections. This protection can last for many years, suggesting that a third dose might not add much extra benefit. The vaccine significantly lowers the risk of cervical cancer, reducing it by about 90%. Overall, evidence supports that both two-dose and three-dose schedules effectively prevent HPV-related health issues. ^{5 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 males and females aged 15-26 who haven't had any HPV vaccine doses. They must be able to consent (with parent's consent if under 18), have a way to pay for the vaccine, speak English or Spanish, and have reliable phone access. It's not for those with many sexual partners, immune/autoimmune disorders, bleeding disorders, pregnant women or those planning pregnancy/birth control non-users.

Inclusion Criteria

Reliable telephone access

Identified source of funding for vaccine which may include Texas Vaccines for Children (VFC) program, Medicaid, the Children's Health Insurance Plan (CHIP), Texas Healthy Women program or other public or private health insurance

Participant and parent/ guardian (if <18) can read and speak either English or Spanish

Exclusion Criteria

I am not pregnant, do not plan to be in the next year, and use birth control.

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

I have a history of immune system issues, like HIV, autoimmune disorders, or have had my spleen removed.

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 Gardasil 9 vaccine over a period of 6 months

6 months

3 visits (in-person)

Follow-up

Participants are monitored for immune response through blood draws at 7 and 12 months

6 months

2 visits (in-person)

Extension

Participants in the 2-dose group receive an optional 3rd dose after the final blood draw at 12 months

1 month

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• 9-valent HPV vaccine

Trial Overview The study is testing whether two doses of the Gardasil 9 HPV vaccine are as effective as three in preventing infection from nine types of HPV in young people. Participants will either receive the standard three-dose schedule or a two-dose schedule with a delayed third dose.

How Is the Trial Designed?

Group I: Males, 2 dose with delayed 3rd dose Experimental Treatment 1 Intervention

Two doses of the 9-valent HPV vaccine to be administered to the experimental group (15-26 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, 2 dose with delayed 3rd dose Experimental Treatment 1 Intervention

Two doses of the 9-valent HPV vaccine to be administered to the experimental group (15-26 years of age) at 0 and 6 months. Additional HPV vaccine dose will be offered after final blood draw at 12 months.

Group III: Females, 3 dose standard Active Control 1 Intervention

Three doses of the 9-valent HPV vaccine to be administered to the comparison group (15-26 years of age) at 0, 2, and 6 months.

Group IV: Males, 3 dose standard Active Control 1 Intervention

Three doses of the 9-valent HPV vaccine to be administered to the comparison group (15-26 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

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]

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 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]

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 (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 two-dose HPV vaccine series for pre-adolescent girls (ages 9-15) is effective in providing protection against HPV 16 and other types, with the World Health Organization recommending this schedule since 2015, while older women still require a three-dose series.

Gardasil9 and Cervarix both show strong efficacy in preventing HPV infections, with Cervarix offering a potentially more cost-effective option due to its sustained high antibody levels and the possibility of effective protection with just one dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HPV vaccines - A review of the first decade. Harper, DM., DeMars, LR.[2022]

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]

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]

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/vaccines.html

HPV Vaccine Efficacy All HPV vaccines have been found to have high efficacy (close to 100%) for prevention of HPV vaccine type-related persistent infection, cervical intraepithelial ...

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

HPV vaccine schedule For the 2-dose schedule, the second shot should be given 6-12 months after the first shot. If the second shot is given less than 5 months after the first shot, ...

4. my.clevelandclinic.org my.clevelandclinic.org/health/treatments/21613-hpv-vaccine

HPV Vaccine: Age, Schedule, Importance & Side Effects So, while Gardasil-9 reduces your risk of cervical cancer by 90%, the original Gardasil reduces your risk by 70%. Cervarix. The FDA approved Cervarix in 2009.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03943875

GARDASIL 9: 3 Dose vs. 2 Dose With Delayed 3rd Dose Biological : 9-valent HPV vaccine, 2 dose efficacy. Evaluate the efficacy of 2 doses of the HPV vaccine across a 12 month period following the 1st dose among ...

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

Human Papillomavirus (HPV) Vaccine Safety ... 3-dose series should be delayed until completion of pregnancy. She may ... Quadrivalent HPV vaccine safety review and US safety monitoring plans for nine-valent ...

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

GARDASIL 9 safety and side effects If the second shot is given less than 5 months after the first shot, a third shot should be given at least 4 months after the second shot. For the 3-dose ...

8. merckvaccines.com merckvaccines.com/gardasil9/dosing-administration/

Dosage and Administration for GARDASIL 9 For the 2-dose schedule, the second dose should be administered 6–12 months after the first dose. If the second dose is administered less than 5 months after ...

9. fda.gov fda.gov/files/vaccines,%20blood%20&%20biologics/published/Package-Insert---Gardasil.pdf

Gardasil Package Insert Page 3. 3. 2. DOSAGE AND ADMINISTRATION. 2.1 Dosage. GARDASIL should be administered intramuscularly as a 0.5-mL dose at the following schedule: 0, 2 months, 6 ...