Gardasil 9 Vaccination Regimen for HPV

Overseen By Johane Seide, MPH

Age: < 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Boston Medical Center

Disqualifiers: Pregnancy, Prior HPV vaccination, Immunocompromised, 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

Compensation: Varies

Number of Visits: 6

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a 2-dose schedule of the Gardasil 9 vaccine generates an immune response as effectively as the standard 3-dose schedule. It focuses on preventing HPV (human papillomavirus) in women aged 16-45. Women currently receiving care at Boston Medical Center who have not been vaccinated for HPV may be suitable candidates. Participants will either receive two doses, with a possible third dose later, or follow the standard three-dose plan. As a Phase 4 trial, this research aims to understand how the FDA-approved and effective Gardasil 9 vaccine can benefit more patients.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What is the safety track record for these treatments?

Research has shown that Gardasil 9 is generally safe and well-tolerated. Both the 2-dose and 3-dose versions have similar safety records. Common side effects include pain, swelling, and redness at the injection site. Some individuals may also experience itching, bruising, bleeding, or a small bump where the shot is given.

The FDA approved Gardasil 9 in 2014, indicating thorough safety studies. Women and girls receiving Gardasil 9 might notice more swelling and redness compared to those who received the earlier version of the vaccine. These side effects are usually mild and resolve on their own.

Overall, evidence suggests that Gardasil 9 is safe. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the Gardasil 9 vaccination regimens because they offer potentially more flexible options for preventing HPV. Unlike the standard 3-dose regimen given over six months, the new 2-dose regimen could simplify the vaccination process by reducing the number of initial doses and adding a rescue dose later if needed. This could make it easier for more people to complete the vaccine series, potentially increasing vaccination rates and broadening protection against HPV.

What evidence suggests that this trial's treatments could be effective for HPV?

This trial will compare two different dosing regimens of Gardasil 9, the HPV vaccine. Studies have shown that Gardasil 9 effectively prevents infections from nine types of HPV. Research indicates that three doses of Gardasil 9 can reduce the risk of HPV-related diseases, such as cervical cancer and genital warts, by about 90%. In this trial, one group will receive the standard three-dose regimen, while another group will receive a two-dose regimen. Studies have shown that the two-dose regimen offers strong and possibly long-lasting protection. Evidence suggests that both the two-dose and three-dose schedules are safe and help the body build a strong defense against HPV infections. Overall, both schedules of Gardasil 9 effectively prevent conditions related to HPV. ^{4 6 7 8 9}

Who Is on the Research Team?

Carl G Streed, MD MPH

Principal Investigator

Boston Medical Center, Internal Medicine

Are You a Good Fit for This Trial?

This trial is for women aged 16-45 who are patients at Boston Medical Center and have not been vaccinated against HPV. They must not be pregnant, breastfeeding, have blood clotting disorders, severe allergies (especially to yeast), or a compromised immune system.

Inclusion Criteria

I am a woman receiving care at Boston Medical Center.

Exclusion Criteria

You've had a severe allergic reaction before, especially to yeast, or you know you're allergic to any part of the vaccine.

I have a blood clotting disorder or low platelet count.

I have received the HPV vaccine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person or phone)

Treatment

Participants receive either a 2-dose or 3-dose regimen of Gardasil 9

6 months

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

1 visit (in-person)

Extension

Participants in the 2-dose group receive a rescue 3rd dose at month 12

1 month

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Gardasil 9 2 dose regimen
• Gardasil 9 3 dose regimen
• Gardasil 9 rescue dose

Trial Overview

The study tests if two doses of Gardasil 9 provide the same immune response in women aged 16-45 as three doses do in those aged 16-26. It also explores the safety of this reduced-dose regimen compared to the standard three-dose schedule.

How Is the Trial Designed?

Group I: Intervention group Experimental Treatment 2 Interventions

240 eligible women will receive a 2-dose regimen of Gardasil 9 at (0 and 6 months, followed by a rescue 3rd dose at month 12)

Group II: Control group Active Control 1 Intervention

120 eligible women will receive the standard 3-dose regimen of Gardasil 9 at (0, 2, 6 months)

Gardasil 9 2 dose regimen is already approved in European Union, United States for the following indications:

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
• Genital warts caused by HPV Types 6 and 11

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
• Genital warts caused by HPV Types 6 and 11

Who Is Running the Clinical Trial?

Boston Medical Center

Lead Sponsor

Trials

410

Recruited

890,000+

Merck Sharp & Dohme LLC

Industry 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

GARDASIL®9, a vaccine designed to prevent diseases caused by nine types of human papillomavirus (HPV), showed a favorable safety profile in nonclinical studies with no treatment-related deaths or adverse effects observed in Sprague-Dawley rats after multiple doses.

The vaccine induced strong immune responses without causing toxicity in both the mothers and their offspring during prenatal and postnatal studies, indicating its potential safety for use in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of a 9-valent HPV vaccine in Sprague-Dawley rats: Nonclinical studies assessing general, reproductive, and developmental toxicity. Wise, LD., Wolf, JJ., Plitnick, LM.[2019]

In a study of 266,647 doses of Gardasil-9® administered in Puglia, Italy, only 22 adverse events following immunization (AEFIs) were reported, resulting in a low reporting rate of 8.25 per 100,000 doses, indicating a favorable safety profile for the vaccine.

Out of the 22 reported AEFIs, only 5 were classified as serious, with 2 leading to hospitalization; however, only 2 serious AEFIs were consistently associated with the vaccine, suggesting that the benefits of Gardasil-9® outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-Life Safety Profile of the 9-Valent HPV Vaccine Based on Data from the Puglia Region of Southern Italy. Di Lorenzo, A., Berardi, P., Martinelli, A., et al.[2022]

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]

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 (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 single dose of the nonavalent HPV vaccine, Gardasil9, was shown to induce stable and high antibody responses for HPV16 and HPV18 in 201 healthy children over a 24-month period, suggesting it could simplify vaccination logistics.

The study demonstrated that antibody levels remained significantly elevated after the initial dose, with a notable boost observed after a delayed booster at 30 months, indicating the potential for long-lasting immunity with fewer doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HPV16/18 Antibody Responses After a Single Dose of Nonavalent HPV Vaccine. Zeng, Y., Moscicki, AB., Woo, H., 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]

Citations

1.

cdc.gov

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

HPV Vaccine Efficacy

Quadrivalent vaccine was also found to have high efficacy (99%) for prevention of genital warts. Among men who have sex with men (MSM), quadrivalent vaccine had ...

2.

fda.gov

fda.gov/media/90064/download

Package Insert - GARDASIL 9

1.3 Limitations of Use and Effectiveness​​ GARDASIL 9 has not been demonstrated to provide protection against disease caused by: • HPV types not covered by the ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8706722/

Human Papillomavirus Vaccine Efficacy and Effectiveness ...

Maximal reductions of approximately 90% for HPV 6/11/16/18 infections, approximately 90% for genital warts, approximately 45% for low-grade cytological cervical ...

4.

merckvaccines.com

merckvaccines.com/gardasil9/efficacy/

Efficacy of GARDASIL®9 (Human Papillomavirus 9-valent ...

If the second dose is administered less than 5 months after the first dose, a third dose should be given at least 4 months after the second dose. For the 3-dose ...

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 ...

Long-term protection in girls and boys who received 2 doses can be inferred based on the demonstration of long-term effectiveness of qHPV and ...

6.

gardasil9.com

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

GARDASIL 9 safety and side effects

The most common side effects of GARDASIL 9 include: pain, swelling, redness, itching, bruising, bleeding, and a lump where your child got the shot.

7.

cdc.gov

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

Human Papillomavirus (HPV) Vaccine Safety

Women and girls who received Gardasil 9 reported higher rates of swelling and redness where the shot was given than those who received Gardasil. Reports of ...

8.

merck.com

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

gardasil_9_pi.pdf

Safety and immunogenicity were assessed in individuals who completed a three-dose vaccination series with GARDASIL 9 and had previously completed a three-dose ...

9.

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 ...