Fractional Dose HPV Vaccine for Human Papillomavirus

Overseen By Virology Research Clinic

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Washington

Must not be taking: Immunosuppressants, Chemotherapy

Disqualifiers: Pregnancy, 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: 4

Duration: Baseline to 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests different doses and types of HPV vaccines to assess their effects on the immune system in adults aged 27-45. Participants will receive a smaller dose of either a bivalent or nonavalent HPV vaccine, administered either into the muscle or under the skin. The goal is to compare immune responses over a year to determine the best vaccination method. Ideal candidates for this trial are those who have not previously received an HPV vaccine and do not plan to get one soon. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment benefits more patients.

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

The trial does not specify if you need to stop taking your current medications. However, if you are on medication that causes significant immunosuppression, you may not be eligible to participate.

What is the safety track record for these treatments?

Research has shown that HPV vaccines are generally safe and well-tolerated. Studies on the bivalent HPV vaccine have found common side effects, such as mild reactions like dizziness, headaches, and nausea, which are usually not serious. Pain or redness at the injection site is also common.

For the nonavalent HPV vaccine, reports indicate that side effects often include pain, swelling, and redness at the injection site. These effects occur slightly more often than with older versions of the vaccine but remain mild.

Both types of HPV vaccines have been closely monitored, with many studies confirming their safety. Most side effects are minor and temporary, and serious side effects are rare. This makes these vaccines a generally safe choice for preventing HPV-related conditions. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments because they explore lower, fractional doses of the HPV vaccine, potentially making immunization more accessible and cost-effective. Unlike the standard full-dose vaccines, this trial investigates the effectiveness of giving just one-fifth of the usual dose, either subcutaneously or intramuscularly. This approach could stretch existing vaccine supplies further and increase vaccination rates, which is crucial for preventing HPV-related diseases globally. Moreover, testing both bivalent and nonavalent types provides insights into optimizing protection against various HPV strains with minimal doses.

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

Research shows that HPV vaccines effectively prevent infections from virus strains that can cause cancer. The bivalent HPV vaccine, even with one dose, is 97.5% effective in preventing infections from HPV types 16 and 18, matching the effectiveness of the full three-dose series. Similarly, the nonavalent HPV vaccine can prevent up to 90% of cervical cancers linked to high-risk HPV types. Studies suggest that even smaller doses of either vaccine still generate a strong immune response, crucial for preventing infections. This trial will explore the potential effectiveness of using smaller doses, with participants receiving either a fractional dose of the bivalent or nonavalent HPV vaccine administered intramuscularly or subcutaneously. ^{5 6 7 8 9}

Who Is on the Research Team?

Helen Stankiewicz Karita, 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 give consent, attend follow-ups, and not have HIV, recent chemo or immunosuppression drugs, unstable health conditions like severe high blood pressure or diabetes, a history of HPV cancer, known allergies to vaccine ingredients, or significant immune system diseases.

Inclusion Criteria

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

Not intending to receive the HPV vaccine series for the duration of the study participation

I am between 27 and 45 years old.

Exclusion Criteria

Known allergy to vaccine components

I am HIV positive.

Any medical condition which, in the opinion of the investigator, may compromise the subject's ability to safely complete the study

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 bivalent or nonavalent HPV vaccine administered intramuscularly or subcutaneously

Baseline to 12 months

Visits at baseline, 4 weeks, 6 months, and 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• HPV vaccine

Trial Overview The study compares two ways of giving a smaller-than-usual dose of HPV vaccines: one group gets the bivalent vaccine intramuscularly (in the muscle) or intradermally (under the skin), while another gets a fractional dose of nonavalent vaccine. The participants' immune responses are checked over a year at set times after vaccination.

How Is the Trial Designed?

Group I: IM Nonavalent HPV vaccine Experimental Treatment 1 Intervention

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

Group II: IM Bivalent HPV vaccine Experimental Treatment 1 Intervention

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

Group III: ID Nonavalent HPV vaccine Experimental Treatment 1 Intervention

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

Group IV: ID 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

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 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]

Cervarix and Gardasil are effective prophylactic HPV vaccines that help prevent cervical cancer by targeting different cancer-causing HPV types, with Cervarix covering five types and Gardasil covering three types plus two that cause genital warts.

Cervarix has demonstrated efficacy for 6.4 years, while Gardasil has shown efficacy for 5 years, highlighting the importance of vaccine duration in reducing cervical cancer risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Currently approved prophylactic HPV vaccines. Harper, DM.[2022]

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 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]

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]

Over 4 years of post-licensure safety surveillance of the HPV-16/18 vaccine (Cervarix) showed that the most commonly reported adverse events were consistent with those expected in the general population, indicating a favorable safety profile.

No significant patterns of serious immune-mediated diseases were found, and the incidences of conditions like Bell's palsy and Guillain-Barré syndrome were within expected ranges, reinforcing the vaccine's acceptable benefit-risk profile for adolescent girls and women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-licensure safety surveillance for human papillomavirus-16/18-AS04-adjuvanted vaccine: more than 4 years of experience. Angelo, MG., Zima, J., Tavares Da Silva, F., et al.[2021]

Both Cervarix and Gardasil HPV vaccines show over 90% efficacy in preventing cervical intraepithelial neoplasia grade 2+ (CIN 2+) caused by HPV 16 and 18 in women aged 16-26 who were initially HPV-negative, indicating strong potential to reduce cervical cancer incidence.

Cervarix not only provides higher efficacy against HPV 31 and 33 compared to Gardasil but also induces a stronger immune response, with significantly higher antibody levels and memory cell responses, while both vaccines have similar safety profiles with mostly mild injection site reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current prophylactic HPV vaccines and gynecologic premalignancies. Harper, DM.[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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11436243/

The Clinical Effectiveness of Single-Dose Human ... In conclusion, the one-dose bivalent vaccination was able to prevent HPV16/18 infections, although some research suggested that two or three ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05291871

Immunogenicity of Fractional Dose of the HPV Vaccines | ... ID Bivalent HPV vaccine. One-fifth fractional dose (0.1 ml) of bivalent HPV vaccine administered subcutaneously. Intervention/Treatment, Biological : HPV ...

3. 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 In a randomized trial in Kenya (KEN SHE), a single-dose of HPV vaccine was found to be 97.5% effective in preventing cancer-causing strains of HPV among 15–20- ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6054558/

Evidence for single-dose protection by the bivalent HPV ... A single dose of the bivalent HPV vaccine could be as efficacious as three doses of the vaccine using the endpoint of persistent HPV infection.

5. mdpi.com mdpi.com/2076-393X/9/12/1413

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% ...

6. 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 ...

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

Human Papillomavirus (HPV) Vaccine Safety HPV vaccines are safe​​ Findings from many vaccine safety monitoring systems and more than 160 studies have shown that HPV vaccines have a favorable safety ...

8. 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 ...

9. ema.europa.eu ema.europa.eu/en/documents/product-information/cervarix-epar-product-information_en.pdf

Cervarix, INN-Human Papillomavirus Vaccine [Types 16, 18 ... The vaccine should under no circumstances be administered intravascularly or intradermally. No data are available on subcutaneous administration of Cervarix.