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

92 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized phase IV trial compares intramuscular and intradermal fractional dose of bivalent HPV vaccine to fractional dose of nonavalent HPV vaccine among men and women aged 27-45 years in Seattle, Washington. Participants will have immune response assessed at baseline, 4 weeks, 6 months, and 12 months

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 data supports the effectiveness of the HPV vaccine treatment?

Research shows that the HPV vaccines, Gardasil and Cervarix, are highly effective in preventing infections with HPV types that cause cervical cancer and genital warts. Both vaccines have shown strong protection against these infections, with Gardasil also preventing vaginal and vulvar lesions, and Cervarix providing additional protection against other cancer-causing HPV types. ^{1 2 3 4 5}

Is the fractional dose HPV vaccine safe for humans?

The HPV vaccines, including Gardasil, Gardasil 9, and Cervarix, have been studied for safety, and while some adverse events (unwanted effects) have been reported, they are generally considered safe. Most reactions, like tenderness at the injection site, are mild, and serious adverse events are rare and not linked to the vaccine. Overall, these vaccines have an acceptable safety profile. ^{6 7 8 9 10}

How is the fractional dose HPV vaccine different from other HPV vaccines?

The fractional dose HPV vaccine is unique because it potentially offers protection with a smaller amount of the vaccine, which could make it more accessible and cost-effective, especially in low-income countries. This approach may still provide strong immunity against HPV infections, similar to the full-dose vaccines like Gardasil and Cervarix. ^{2 4 5 10 11}

Research Team

Helen Stankiewicz Karita, MD

Principal Investigator

University of Washington

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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, 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]

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]

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]

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]

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]

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 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]

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]

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]

References

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

An update of prophylactic human papillomavirus L1 virus-like particle vaccine clinical trial results. [2022]

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

HPV vaccines - A review of the first decade. [2022]

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

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

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

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

5. England pubmed.ncbi.nlm.nih.gov

Currently approved prophylactic HPV vaccines. [2022]

6. England pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

Post-licensure safety surveillance for human papillomavirus-16/18-AS04-adjuvanted vaccine: more than 4 years of experience. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

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

9. United States 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. [2021]

10. Netherlands pubmed.ncbi.nlm.nih.gov

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

11. England pubmed.ncbi.nlm.nih.gov

Current prophylactic HPV vaccines and gynecologic premalignancies. [2022]