Gardasil HPV Vaccine for Human Papillomavirus

(PROTECT Trial)

Recruiting at 2 trial locations

Overseen By Onyinyechi Ogbumbadiugha-Weekes, MPH

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University of Maryland, Baltimore

Must be taking: Androgen blockers, Estrogen

Must not be taking: Chemotherapy, Immunomodulants

Disqualifiers: Born female, Hypersensitivity, 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: 4

Duration: 6 months

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the Gardasil9 vaccine to evaluate its effectiveness in boosting the immune system against the human papillomavirus (HPV). The focus is on individuals born male who have used or are using hormone treatments, such as androgen blockers or estrogen, including those living with HIV and those without. Participants will receive the vaccine and have their immune response assessed after the final dose. Suitable candidates for this trial are HIV-positive or HIV-negative individuals, born male, who have used hormone treatments or have had sexual contact with a person with a penis in the past year. As a Phase 2 trial, this research aims to measure the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant medical advancements.

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 on treatments like systemic chemotherapy or certain immune-affecting drugs, you may not be eligible to participate.

Is there any evidence suggesting that Gardasil9 is likely to be safe for humans?

Research has shown that Gardasil9, the HPV vaccine being tested, is generally safe. Common side effects include pain, redness, and swelling at the injection site. Some individuals might also experience mild reactions such as headaches or dizziness. These effects resemble those caused by other vaccines and are usually not serious. Serious side effects, such as fainting, occur rarely. No evidence links the vaccine to infertility or other long-term health problems. The vaccine's approval for use in other groups suggests a good safety record. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike other treatments for human papillomavirus (HPV) prevention, Gardasil9 is noteworthy because it covers nine different HPV strains, offering broader protection compared to earlier vaccines that cover fewer strains. Researchers are particularly excited about this treatment for its potential to protect individuals with unique health backgrounds, such as those with past exposure to hormone treatments, who may have different immune responses. This expanded protection could significantly reduce HPV-related health issues in these populations, making Gardasil9 a promising advancement in HPV prevention.

What evidence suggests that Gardasil9 might be an effective treatment for HPV?

Research has shown that the Gardasil9 vaccine effectively protects against HPV, a common virus. Over 98% of recipients develop an immune response to the virus. This trial will administer the Gardasil9 vaccine to participants in different groups. One group includes people born male with current or past exposure to androgen blockers or estrogen, while another group includes HIV-negative individuals who are either in the same category or are men who have had sex with a person with a penis. The vaccine can prevent up to 90% of infections from certain types of HPV linked to cancers and genital warts. It has been proven to lower the risk of several diseases related to HPV. The vaccine is safe and provides strong protection for many people. ^{6 7 8 9 10}

Who Is on the Research Team?

Omar Harfouch, MD

Principal Investigator

University of Maryland, Baltimore

Are You a Good Fit for This Trial?

This trial is for individuals born male, aged 18-70, who may or may not be living with HIV. It's specifically for those who identify as transgender, non-binary, gender diverse, or have had sexual relations with another person with a penis in the past year. Participants should not have received the Gardasil9 vaccine before and must be able to consent.

Inclusion Criteria

I can understand and agree to the study's procedures and risks.

I am living with HIV.

I do not have HIV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a 3-dose series of the Gardasil9 vaccine at Day 0, Month 2, and Month 6

6 months

3 visits (in-person)

Follow-up

Participants are monitored for immune response and safety 1 month after the final vaccine dose

1 month

1 visit (in-person)

Optional Follow-up

Participants with anal dysplasia at study entry may have an optional visit for repeat HRA and additional sample collection

What Are the Treatments Tested in This Trial?

Interventions

• Gardasil9

Trial Overview

The study tests how well the Gardasil9 HPV vaccine works in people assigned male at birth who are taking hormones like estrogen or androgen blockers. The vaccine will be given three times over six months to both HIV-positive and HIV-negative groups to compare immune responses.

How Is the Trial Designed?

Group I: People born male with current or past exposure to androgen blockers or estrogen (BM-EABE) Experimental Treatment 1 Intervention

One dose of human papillomavirus (HPV) vaccine, 9-valent (Gardasil9) will be administered on Day 0, Month 2, and Month 6

Group II: HIV Negative BM-EABE or HIV Negative men who had sex with a person with a penis (MSPP) Active Control 1 Intervention

One dose of human papillomavirus (HPV) vaccine, 9-valent (Gardasil9) will be administered on Day 0, Month 2, and Month 6

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Published Research Related to This Trial

In a study involving 12,066 women aged 9 to 26 years who received the HPV vaccines Gardasil® and Cervarix® over three years, 61% reported experiencing mild and transient adverse events after the first dose.

The high rate of reported adverse events is attributed to the study's design, which encouraged participants to document all occurrences, highlighting the importance of ongoing surveillance for vaccine safety, especially for newly marketed vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Human papillomavirus vaccine register]. Spila-Alegiani, S., Da Cas, R., Giambi, C., et al.[2013]

The introduction of the quadrivalent vaccine Gardasil and the bivalent vaccine Cervarix has significantly advanced the prevention of HPV-related diseases, including various cancers and benign conditions like genital warts.

A new multivalent vaccine, Gardasil 9, has been approved and shows promise in providing broader protection against nine HPV subtypes, with ongoing efforts to improve vaccine accessibility and reduce production costs, especially in developing countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second-generation prophylactic HPV vaccines: current options and future strategies for vaccines development. Fruscalzo, A., Londero, AP., Bertozzi, S., et al.[2016]

The post-licensure safety profile of HPV vaccines Gardasil and Cervarix was evaluated using data from three sources, including VigiBase and VAERS, confirming that the reported adverse events align with existing safety data.

The analysis showed that the safety profiles of both vaccines are consistent with the information provided in their Summary of Product Characteristics (SPC), indicating that they are safe for public use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postlicensure safety evaluation of human papilloma virus vaccines. Labadie, J.[2015]

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]

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 new nonavalent HPV vaccine (9vHPV) shows a very strong immune response with nearly 100% seroconversion rates and has a safety profile similar to the quadrivalent vaccine (qHPV), although it may cause more local reactions like swelling, especially when given with other vaccines.

The 9vHPV vaccine offers additional protection against HPV-related cancers, potentially preventing 8% to 18% more cases compared to previous vaccines, but its overall impact will depend on various factors such as duration of protection and population-specific HPV type distribution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on the 9-valent HPV vaccine. Lopalco, PL.[2018]

In a study involving 741 healthy girls aged 9-15, co-administration of the HPV-16/18 vaccine with the hepatitis B vaccine met non-inferiority criteria for immune responses, showing that both vaccines can be effectively given together without compromising their efficacy.

The co-administered vaccines were well tolerated, with high seroprotection rates achieved for both hepatitis B (97.9% to 100%) and HPV (≥99%), indicating that this combination is safe and effective for adolescent girls.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Co-administration of human papillomavirus-16/18 AS04-adjuvanted vaccine with hepatitis B vaccine: randomized study in healthy girls. Schmeink, CE., Bekkers, RL., Josefsson, A., 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 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 Gardasil vaccine significantly increased the intersurgical interval (ISI) by an average of 3.1 months in patients with recurrent respiratory papillomatosis (RRP), indicating a positive effect on disease management.

40% of patients achieved complete remission and 25% experienced partial remission, with males showing a greater response compared to females, suggesting that the vaccine can effectively modulate the severity of RRP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of the quadrivalent human papillomavirus vaccine (gardasil) as adjuvant therapy in the treatment of recurrent respiratory papilloma. Young, DL., Moore, MM., Halstead, LA.[2015]

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.

merckvaccines.com

merckvaccines.com/gardasil9/efficacy/

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

Efficacy against certain HPV-related cancers and diseases in individuals aged 16-26 · ~98% · 100% · 100% · ~75% · ~97% · ~88% · 95%.

2.

cdc.gov

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

HPV Vaccine Efficacy

More than 98% of recipients develop an antibody response to HPV types included in the respective vaccines 1 month after completing a full vaccination series.

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.

merck.com

merck.com/news/merck-announces-positive-top-line-results-from-phase-3-trial-evaluating-efficacy-and-safety-of-gardasil9-in-japanese-males/

Merck Announces Positive Top-line Results from Phase 3 ...

The trial met its primary and secondary endpoints demonstrating that administration of a 3-dose regimen of GARDASIL 9 reduced the combined incidence of ...

5.

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 ...

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

Gardasil 9, Gardasil and Cervarix · The most common side effect reported was pain, swelling, and redness in the arm where the shot was given. · These mild side ...

8.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40662677/

Adverse events following 9-valent human papillomavirus ...

Among reported events, most were non-serious and consistent with known reactogenicity patterns, including syncope, headache, and injection site ...

9.

fda.gov

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

Gardasil Package Insert

The injection site adverse reactions that were observed among recipients of GARDASIL at a frequency of at least 1.0% and also at a greater frequency than that ...

10.

cancer.gov

cancer.gov/news-events/cancer-currents-blog/2021/hpv-vaccine-parents-safety-concerns

Parent Concerns About HPV Vaccine Safety Increasing - NCI

The most common serious side effects of HPV vaccination are dizziness and fainting. There is no evidence that HPV vaccines lead to infertility ...