HPV Vaccine Comparison for Human Papillomavirus

Overseen By UW Virology Research Clinic

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Washington

Disqualifiers: Immune disorder, HIV, Cancer, 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 8 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: Baseline

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of different HPV vaccines in men and women aged 27-45 who have not yet received an HPV vaccine. Researchers aim to determine if a small dose of either a bivalent (two-strain) or nonavalent (nine-strain) HPV vaccine can effectively boost the immune system against the virus. They will monitor immune responses over two years to assess vaccine effectiveness. Ideal candidates are those in this age group who have never received an HPV vaccine and are willing to attend follow-up visits. As a Phase 4 trial, this research involves an FDA-approved treatment and seeks to understand its benefits for more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have an unstable medical condition or are undergoing chemotherapy, you may not be eligible to participate.

What is the safety track record for these treatments?

Research has shown that both the nonavalent and bivalent HPV vaccines are generally safe. For the nonavalent HPV vaccine, studies have found that most side effects are mild, with common reports of pain, redness, or swelling at the injection site. Other frequent reactions include dizziness and headaches.

The bivalent HPV vaccine causes similar mild reactions, such as redness and swelling at the injection site, along with fever and headaches. Both vaccines have been approved and used widely, demonstrating their safety. Although rare, some individuals may experience more serious side effects, like seizure-like reactions.

In the current trial, the vaccines are administered in smaller doses, which might further reduce the likelihood of side effects. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments because they offer a potential solution to vaccine accessibility and cost issues for HPV prevention. Unlike the standard full-dose vaccines, the nonavalent and bivalent HPV vaccines in this trial are administered as one-fifth fractional doses. This new delivery method could make the vaccines more affordable and easier to distribute, especially in resource-limited settings. Additionally, these fractional doses could retain effectiveness while reducing costs, making widespread HPV vaccination more feasible globally.

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

This trial will compare the effectiveness of the bivalent and nonavalent HPV vaccines. Studies have shown that both vaccines effectively prevent infections from high-risk HPV types. Research indicates that the nonavalent vaccine is 97.5% effective against these types. Similarly, the bivalent vaccine also demonstrates 97.5% effectiveness against high-risk HPV. These vaccines offer strong protection, with over 98% of recipients developing an immune response to the HPV types they cover. This robust evidence underscores the vaccines' effectiveness in preventing HPV infections. ^{6 7 8 9 10}

Who Is on the Research Team?

Anna Wald, MD

Principal Investigator

University of Washington

Are You a Good Fit for This Trial?

This trial is for men and women aged 27-45 in Seattle who haven't had the HPV vaccine and won't get it during the study. They must be able to follow the trial schedule. People with immune issues, cancer treatments, HIV risk without recent negative tests, unstable health conditions like severe hypertension or uncontrolled diabetes, a history of HPV-related cancer, pregnancy or breastfeeding, or allergies to vaccine ingredients can't join.

Inclusion Criteria

Age 27-45 years at enrollment

Willing and able to provide written informed consent, undergo clinical evaluation, and adhere to follow-up schedule

You do not plan on getting the HPV vaccine during the study.

Exclusion Criteria

Cancer or chemotherapy (current, within 6 months, or anticipated in the future) except for fully excised non-melanoma skin cancer)

You have a weakened immune system or a disorder that affects your immune system.

HIV infection or continued high risk for HIV; patients at risk for HIV who do not have a negative HIV test in the last 6 months will be excluded

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a fractional dose of either the bivalent or nonavalent HPV vaccine administered subcutaneously

Baseline

1 visit (in-person)

Follow-up

Participants are monitored for immune response at 4 weeks, 6 months, 12 months, and 24 months after vaccination

24 months

4 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• HPV vaccine

Trial Overview The study compares two fractional doses of different HPV vaccines: bivalent versus nonavalent. Participants' immune responses are checked over two years at specific intervals (baseline, after 4 weeks, then at 6 months, 12 months and finally at 24 months).

How Is the Trial Designed?

Group I: Nonavalent HPV vaccine Experimental Treatment 1 Intervention

One-fifth fractional dose (0.1 ml) of nonavalent HPV vaccine administered subcutaneously

Group II: Bivalent HPV vaccine Experimental Treatment 1 Intervention

One-fifth fractional dose (0.1 ml) of bivalent HPV vaccine administered subcutaneously

HPV vaccine is already approved in United States, European Union, Canada, Switzerland, United Kingdom for the following indications:

Approved in United States as Gardasil 9 for:

• Prevention of cervical, vulvar, vaginal, and anal cancers caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58
• Prevention of genital warts caused by HPV types 6 and 11

Approved in European Union as Gardasil 9 for:

• Prevention of cervical, vulvar, vaginal, and anal cancers caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58
• Prevention of genital warts caused by HPV types 6 and 11

Approved in Canada as Gardasil 9 for:

• Prevention of cervical, vulvar, vaginal, and anal cancers caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58
• Prevention of genital warts caused by HPV types 6 and 11

Approved in Switzerland as Gardasil 9 for:

• Prevention of cervical, vulvar, vaginal, and anal cancers caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58
• Prevention of genital warts caused by HPV types 6 and 11

Approved in United Kingdom as Gardasil 9 for:

• Prevention of cervical, vulvar, vaginal, and anal cancers caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58
• Prevention of genital warts caused by HPV types 6 and 11

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Published Research Related to This Trial

In a study involving 198 girls aged 12-15, the tetravalent HPV vaccine Gardasil® demonstrated a comparable safety profile to the bivalent HPV vaccine Cervarix®, with most local and systemic reactions being mild and infrequent.

Severe tenderness at the injection site was reported more frequently in the Cervarix® group (24%) compared to the Gardasil® group (7%), indicating that Gardasil® may be associated with fewer injection site reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reactogenicity of Cervarix and Gardasil human papillomavirus (HPV) vaccines in a randomized single blind trial in healthy UK adolescent females. Haskins-Coulter, T., Southern, J., Andrews, N., et al.[2021]

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]

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]

Both Gardasil and Cervarix HPV vaccines have shown outstanding efficacy in preventing infections and related conditions in young women, with excellent safety profiles and only mild to moderate side effects reported.

Neither vaccine is effective in treating existing HPV infections or lesions, but they provide strong protection against specific HPV types for at least four years, with Gardasil also preventing genital warts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update of prophylactic human papillomavirus L1 virus-like particle vaccine clinical trial results. Schiller, JT., Castellsagué, X., Villa, LL., et al.[2022]

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]

Cervarix, an HPV vaccine, has shown a 70.2% reduction in cervical precancerous lesions in HPV-naïve young girls, indicating its strong efficacy in preventing cervical cancer caused by HPV types 16, 18, 31, 33, and 45.

Cervarix induces significantly higher levels of neutralizing antibodies and memory immune cells compared to Gardasil, with sustained protection lasting over 7 years, demonstrating its long-term effectiveness and safety in preventing HPV-related diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical update of the AS04-adjuvanted human papillomavirus-16/18 cervical cancer vaccine, Cervarix. Schwarz, TF.[2020]

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 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 Gardasil® and Cervarix® vaccines are highly effective and safe in preventing cervical cancer caused by human papillomaviruses (HPV), which is the third most common cancer in women.

Current research is focused on developing more affordable second-generation HPV vaccines using different formulations, as the high cost of existing vaccines limits their global implementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylactic papillomavirus vaccines. Ribeiro-Müller, L., Müller, M.[2022]

Citations

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

Human Papillomavirus Vaccine Efficacy and Effectiveness ... The bivalent HPV vaccine efficacy against prevent persistent HPV 16/18 infection in adult, previously uninfected women was 83% (95% CI = 71% to 90%) and 43% ( ...

2. cdc.gov cdc.gov/hpv/hcp/vaccination-considerations/safety-and-effectiveness-data.html

HPV Vaccine Safety and Effectiveness Data More than 15 years of monitoring and research have accumulated reassuring evidence that HPV vaccination provides safe, effective, and long-lasting protection.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8724969/

EFFICACY OF THE BIVALENT HPV VACCINE AGAINST ... Large pre-licensure trials of bivalent and quadrivalent vaccines demonstrated high protection against HPV 16 and 18 persistent infection and associated cervical ...

4. publichealth.jhu.edu publichealth.jhu.edu/ivac/the-power-of-a-single-dose-evidence-for-a-single-dose-hpv-vaccine-schedule

Evidence for a Single-Dose HPV Vaccine Schedule After 18 months of follow-up, both the bivalent and nonavalent vaccines demonstrated 97.5% vaccine efficacy against high-risk strains of HPV.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0002817719307378

Summary of the evidence on the safety, efficacy, and ... Systematic reviews have found evidence that the available HPV vaccines are safe, effective, and efficacious against vaccine-type HPV infection and HPV- ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6256007/

Safety of bivalent human papillomavirus vaccine in the US ... Data from prelicensure clinical trials and postlicensure safety monitoring indicate that injection site reactions, fever, headache, nausea, dizziness, malaise ...

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

Human Papillomavirus (HPV) Vaccine Safety To date, no adverse events related to this lot of HPV vaccine have been reported other than mild reactions such as redness and swelling at the injection site.

8. fda.gov fda.gov/media/78013/download

cervarix, suspension for intramuscular injection The safety of CERVARIX was evaluated by pooling data from controlled and uncontrolled. 66 clinical trials involving 23,952 females 9 through 25 years of age ...

9. drugs.com drugs.com/cervarix.html

Cervarix HPV Vaccine: Schedule, Side Effects, Warnings Some people have had seizure-like reactions after receiving a human papilloma virus vaccine. Your doctor may want you to remain under ...

10. aafp.org aafp.org/pubs/afp/issues/2010/1215/p1541.html

Bivalent HPV Recombinant Vaccine (Cervarix) for the ... SAFETY. Safety concerns include minor injection site reactions and general adverse effects similar to those of other vaccines. The tip cap ...