HPV Vaccine for Anal Cancer Prevention

Not yet recruiting at 3 trial locations

Overseen By Grecia Higuerey

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must be taking: cART

Disqualifiers: Hypersensitivity, Anogenital cancer, Previous HPV immunization

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of the 9-valent HPV vaccine in preventing high-grade anal dysplasia, a condition that can lead to cancer, in HIV-positive men who have sex with men (MSM). Researchers are assessing the vaccine's safety and efficacy in this group. Participants will receive either immediate or delayed doses of the vaccine. Men who have engaged in sexual activity with other men and have a biopsy-confirmed condition called AIN-2 or -3 in the anal canal may be suitable for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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 cART (HIV treatment), you must be on a stable regimen for at least six months.

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

Research has shown that the 9-valent HPV vaccine, Gardasil 9, is generally safe. Studies have found that this vaccine protects against nine types of HPV linked to several cancers, including anal cancer. Gardasil 9 is approved for use in males aged 9 to 45 to help prevent certain HPV-related cancers.

The vaccine is well-tolerated, with most side effects being mild, such as pain, swelling, or redness at the injection site, and occasionally a mild fever. Serious side effects are rare. Evidence suggests that the vaccine effectively reduces the risk of HPV-related diseases, making it a promising option for preventing anal cancer in at-risk groups. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the 9-valent HPV vaccine for anal cancer prevention because it targets nine HPV types, offering broader protection than earlier vaccines. Unlike other treatments that primarily focus on treating existing HPV-related conditions, this vaccine aims to prevent the onset of cancer by tackling the virus before it can cause harm. This proactive approach could significantly reduce the incidence of anal cancer, providing a more comprehensive and preventive strategy than current treatments that often involve surgery or chemotherapy.

What evidence suggests that the 9-valent HPV vaccination might be an effective treatment for anal cancer prevention?

Research shows that the 9-valent HPV vaccine effectively prevents cancers caused by HPV types 16 and 18, including anal cancer. Studies have found that this vaccine protects against nine different types of HPV, which cause most HPV-related cancers. Evidence indicates that the vaccine can greatly reduce the risk of anal cancer, especially if administered before exposure to these HPV types. The vaccine is safe and effective in preventing these cancers. In this trial, participants will receive the 9-valent HPV vaccination either immediately or on a delayed schedule. Early vaccination can prevent many cases of anal cancer, making it a promising method to reduce the disease among at-risk individuals. ^{5 6 7 8 9}

Who Is on the Research Team?

Irving Salit, MD

Principal Investigator

Toronto General Hospital, University Health Network

Are You a Good Fit for This Trial?

This trial is for HIV-positive men who have had sexual activity with men or both genders, are at least 18 years old, and have high-grade anal dysplasia (AIN-2 or -3). They must be willing to undergo standard ablative therapy and either be on a stable antiretroviral regimen or not planning to start one within six months. Participants need documented HIV infection and the ability to attend all study visits.

Inclusion Criteria

I have had sexual relations with men or both men and women.

I can go to all required clinic visits for the study.

I have had sexual activity with men or both men and women.

Exclusion Criteria

I have or had cancer in the genital, anal, rectal, or throat areas.

You are allergic to any ingredient in the HPV vaccine, like yeast or aluminum.

I have been vaccinated against HPV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Immediate Vaccination

Administration of dose #1 of 9-valent HPV vaccination at baseline visit, dose #2 at month 2, and dose #3 at month 6

6 months

3 visits (in-person)

Delayed Vaccination

Administration of dose #1 of 9-valent HPV vaccination at month 12, dose #2 at month 14, and dose #3 at month 18

6 months

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in anal carriage of vaccine HPV types and immunogenicity

24 months

What Are the Treatments Tested in This Trial?

Interventions

• 9-valent HPV vaccination

Trial Overview The trial is testing the safety and effectiveness of the 9-valent HPV vaccine in preventing recurrence of high-grade anal lesions in HIV-positive MSM. It explores how well this vaccine works as part of their overall health management strategy.

How Is the Trial Designed?

Group I: Immediate Vaccination Experimental Treatment 1 Intervention

Administration of dose #1 of 9-valent HPV vaccination will be given at baseline visit, dose #2 at month 2, and dose #3 at month 6.

Group II: Delayed Vaccination Active Control 1 Intervention

Administration of dose #1 of 9-valent HPV vaccination will be given at month 12, dose #2 at month 14, and dose #3 at month 18.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

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

The nonavalent HPV vaccine (9vHPV) has shown over 90% efficacy in preventing cervical, vulvar, and vaginal precancers caused by HPV types 16, 18, and five additional cancer-causing types (31, 33, 45, 52, 58) in Phase III clinical studies.

9vHPV has the potential to prevent up to 93% of cervical cancer cases and has demonstrated lasting antibody responses for at least five years, indicating its long-term effectiveness in reducing the burden of HPV-related cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant human papillomavirus nonavalent vaccine in the prevention of cancers caused by human papillomavirus. Toh, ZQ., Kosasih, J., Russell, FM., et al.[2020]

The nine-valent HPV (9vHPV) vaccine demonstrated comparable immune responses to the quadrivalent HPV (qHPV) vaccine for HPV types 6/11/16/18, while also effectively eliciting immune responses for five additional oncogenic HPV types (31/33/45/52/58) in a study of 500 men aged 16-26.

Both the 9vHPV and qHPV vaccines exhibited similar safety profiles, indicating that the 9vHPV vaccine is a safe and effective option for preventing a broader range of HPV-related diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase III clinical study to compare the immunogenicity and safety of the 9-valent and quadrivalent HPV vaccines in men. Van Damme, P., Meijer, CJLM., Kieninger, D., et al.[2017]

The 9-valent HPV vaccine (9vHPV) can potentially increase the prevention of cervical cancer from 70% to 90% by covering additional HPV types (31, 33, 45, 52, and 58) not included in earlier vaccines.

In addition to cervical cancer, the 9vHPV vaccine could prevent 85-95% of HPV-related vulvar, vaginal, and anal cancers, highlighting its broad efficacy in reducing the overall cancer burden associated with HPV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

9-Valent HPV vaccine for cancers, pre-cancers and genital warts related to HPV. Pitisuttithum, P., Velicer, C., Luxembourg, A.[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 9-valent HPV vaccine (9vHPV) is safe and highly effective, showing over 99.8% seroconversion rates for all vaccine types in both groups of a study involving 1054 participants aged 11-15 years.

Administering the 9vHPV vaccine alongside the REPEVAX vaccine did not interfere with the immune response to either vaccine, indicating that this approach can safely reduce the number of vaccination visits needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open-label, randomized study of a 9-valent human papillomavirus vaccine given concomitantly with diphtheria, tetanus, pertussis and poliomyelitis vaccines to healthy adolescents 11-15 years of age. Kosalaraksa, P., Mehlsen, J., Vesikari, T., et al.[2015]

The 9-valent HPV vaccine (9vHPV) is as effective as the quadrivalent HPV vaccine (qHPV) in generating immune responses against HPV types 6, 11, 16, and 18, while also providing a 96.7% risk reduction against high-grade cervical, vulvar, or vaginal diseases related to five additional HPV types in females aged 16-26.

The 9vHPV vaccine has been shown to be safe and well tolerated, with evidence supporting its efficacy in both males and females aged 9-26, indicating its potential to significantly expand protection against HPV infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human papillomavirus 9-valent vaccine for cancer prevention: a systematic review of the available evidence. Signorelli, C., Odone, A., Ciorba, V., 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]

Citations

1. 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 ...

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

HPV Vaccine Efficacy 9-valent HPV vaccine (Gardasil-9 [23 pages]) is a non-infectious recombinant ... Quadrivalent vaccine was also found to have high efficacy (99%) for prevention of ...

3. merckvaccines.com merckvaccines.com/gardasil9/efficacy/

Efficacy of GARDASIL®9 (Human Papillomavirus 9-valent ... GARDASIL 9 is indicated in males 9 through 45 years of age for the prevention of anal, oropharyngeal and other head and neck cancers caused by HPV Types 16, 18 ...

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

Human Papillomavirus Vaccine Efficacy and Effectiveness ... The bivalent HPV vaccine (at least one dose) among young women who were previously uninfected showed a vaccine efficacy (VE) of 91–100% (95% CI = 64.6% to 86% ...

5. hpvworld.com hpvworld.com/articles/early-hpv-vaccination-could-reduce-anal-cancer-incidence/

Early HPV vaccination could reduce anal cancer incidence Vaccination of children and adolescents with 9vHPV is expected to prevent a large majority of anal cancer cases while HPV vaccination of adults, after sexual ...

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

Human Papillomavirus (HPV) Vaccine Safety The 9vHPV vaccine adds 5 additional antigens, providing protection against 9 types of cancer-causing human papillomaviruses.

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

GARDASIL 9 safety and side effects GARDASIL 9 does not prevent all types of cervical, vulvar, vaginal, anal, or head and neck cancers. Vaccination does not remove the need for recommended cancer ...

8. fda.gov fda.gov/media/90064/download

Package Insert - GARDASIL 9 GARDASIL 9 has not been demonstrated to provide protection against disease caused by: • HPV types not covered by the vaccine [see Description (11)],. • HPV ...

9. merckvaccines.com merckvaccines.com/gardasil9/

GARDASIL®9 (Human Papillomavirus 9-valent Vaccine, ... GARDASIL 9 is indicated in males 9 through 45 years of age for the prevention of anal, oropharyngeal and other head and neck cancers caused by HPV Types 16, 18 ...