Gardasil HPV Vaccine for Human Papillomavirus

(PROTECT Trial)

Recruiting at 1 trial location

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

Trial Summary

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.

What data supports the effectiveness of the drug Gardasil9 for preventing human papillomavirus?

Gardasil9 is shown to be effective in preventing HPV infections that can lead to cervical cancer by covering more HPV types than earlier vaccines, increasing protection from about 70% to 90%. Clinical trials demonstrated that Gardasil9 is safe and effective, with strong immune responses in both young women and younger boys and girls. ^{1 2 3 4 5}

Is the Gardasil HPV vaccine generally safe for humans?

The Gardasil HPV vaccine, including Gardasil 9, has been studied for safety, and while some adverse events have been reported, they are generally rare. Most side effects are not serious, and the vaccine's safety profile is considered favorable with a low rate of serious adverse events. ^{2 6 7 8 9}

How does Gardasil9 differ from other HPV vaccines?

Gardasil9 is unique because it protects against nine types of HPV, including five additional types beyond the original Gardasil, increasing protection from about 70% to 90% against HPV-related cancers. This expanded coverage makes it more effective in preventing a wider range of HPV-related diseases. ^{3 4 6 10 11}

What is the purpose of this trial?

This is a phase 2, open-label study to assess the immunogenicity of the 9-valent human papillomavirus (HPV) recombinant vaccine (Gardasil9) in people born male with current or past exposure to androgen blockers or estrogen (BM-EABE). Investigators will enroll BM-EABE with HIV and HIV negative controls (BM-EABE or men who have sex with a person with a penis (MSPP)) and administer Gardasil9 at timepoints Day 0, Month 2, and Month 6. The immune response to the vaccine will be analyzed at Month 7 (1 month following the final vaccine dose).

Research Team

Omar Harfouch, MD

Principal Investigator

University of Maryland, Baltimore

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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 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]

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]

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 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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Co-administration of human papillomavirus-16/18 AS04-adjuvanted vaccine with hepatitis B vaccine: randomized study in healthy girls. [2022]

2. Italy pubmed.ncbi.nlm.nih.gov

[Human papillomavirus vaccine register]. [2013]

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

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

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

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

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

The use of the quadrivalent human papillomavirus vaccine (gardasil) as adjuvant therapy in the treatment of recurrent respiratory papilloma. [2015]

6. Netherlands pubmed.ncbi.nlm.nih.gov

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

7. Netherlands pubmed.ncbi.nlm.nih.gov

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

8. Switzerland 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. [2022]

9. England pubmed.ncbi.nlm.nih.gov

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

10. New Zealand pubmed.ncbi.nlm.nih.gov

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

11. Italy pubmed.ncbi.nlm.nih.gov

Second-generation prophylactic HPV vaccines: current options and future strategies for vaccines development. [2016]