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

757 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

We are evaluating whether 15-26 year old males and females need a 3rd dose of the human papillomavirus (HPV) vaccine, or whether 2 doses provide similar protection as 3 doses from the 9 types of HPV that it protects against.

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.

Is the 9-valent HPV vaccine safe for humans?

The 9-valent HPV vaccine, also known as Gardasil 9, has been shown to be generally safe in humans. Most side effects are mild, such as soreness at the injection site, and serious side effects are rare. ^{1 2 3 4 5}

How is the 9-valent HPV vaccine different from other HPV vaccines?

The 9-valent HPV vaccine (Gardasil 9) is unique because it protects against nine different types of HPV, including those most commonly associated with cervical cancer and other HPV-related diseases, whereas earlier vaccines like the quadrivalent and bivalent versions cover fewer types. It offers broader protection and is administered in a flexible dosing schedule, which may improve vaccine uptake. ^{1 2 6 7 8}

What data supports the effectiveness of the drug Gardasil 9 for HPV prevention?

Gardasil 9, a 9-valent HPV vaccine, has been shown to increase protection against cervical cancer from about 70% to 90% by covering additional HPV types. Clinical trials demonstrated that it is safe and effective, with strong immune responses in both young women and younger boys and girls. ^{1 2 3 9 10}

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

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 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]

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 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]

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 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 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]

Citations

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

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

2. Czech Republic pubmed.ncbi.nlm.nih.gov

[Nine-valent HPV vaccine - new generation of HPV vaccine]. [2018]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Safety of 9-valent human papillomavirus vaccine administered to males and females in routine use. [2023]

4. 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]

5. 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]

6. 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]

7. England pubmed.ncbi.nlm.nih.gov

OAE-based data mining and modeling analysis of adverse events associated with three licensed HPV vaccines. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Randomized controlled trial of two dosing schedules for human papillomavirus vaccination among college age males. [2021]

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

HPV vaccines - A review of the first decade. [2022]

10. Netherlands 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. [2020]