RG1-VLP Vaccine for HPV-Related Cancers

Recruiting at 2 trial locations

Age: 18 - 65

Sex: Female

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Genital warts, Cancer treatment, Auto-immune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

Duration: 6 months

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new vaccine, RG1-VLP, which could prevent cancers linked to certain rare types of human papillomavirus (HPV) not covered by current vaccines. Researchers seek to determine if RG1-VLP is safe and can effectively trigger the body's immune response. Women who have not received HPV vaccines and are concerned about HPV-related cancers might be suitable for this trial. Participants will receive the RG1-VLP vaccine and possibly the Gardasil-9 vaccine later, with close monitoring for any side effects. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this potentially groundbreaking vaccine.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using immunosuppressive drugs or certain vaccines around the time of the trial vaccinations.

Is there any evidence suggesting that the RG1-VLP vaccine is likely to be safe for humans?

Past studies have shown that HPV vaccines are safe, with most side effects being mild, such as soreness at the injection site. Research suggests that the RG1-VLP vaccine, currently under testing for HPV-related cancers, might have a similar safety profile. Current HPV vaccines, like Gardasil-9, have proven effective and safe in preventing HPV infections and related cancers. Since RG1-VLP aims to protect against more types of HPV, researchers are carefully studying its safety. As this trial is in its early stages, researchers are focused on ensuring it is well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the RG1-VLP vaccine for HPV-related cancers because it offers a potential new way to prevent these cancers by targeting a broader range of HPV types. Unlike existing vaccines like Gardasil-9, which primarily cover the most common cancer-causing HPV strains, RG1-VLP aims to provide even wider protection by including additional HPV strain targets. This broader coverage could potentially reduce the incidence of HPV-related cancers even further, making it a promising option for enhanced prevention.

What evidence suggests that the RG1-VLP vaccine might be an effective treatment for HPV-related cancers?

Research has shown that the RG1-VLP vaccine, which participants in this trial may receive, could effectively combat HPV infections. Studies have found that this vaccine works well against many HPV types linked to certain cancers. It activates the body's defense system, similar to the licensed vaccine Cervarix, by producing neutralizing antibodies. This helps the body recognize and fight the virus before it can cause harm. By targeting a different part of the virus, RG1-VLP might protect against HPV types not covered by current vaccines. Overall, early findings suggest that RG1-VLP may offer a new way to prevent HPV-related cancers. ^{2 3 5 6 7}

Who Is on the Research Team?

Reinhard Kirnbauer

Principal Investigator

Medical University of Vienna

Are You a Good Fit for This Trial?

This trial is for women aged 18-45 with normal blood counts and organ function, not pregnant or breastfeeding, without HPV-related diseases or abnormal Pap smears (if over 25), no history of severe allergies to vaccines, and not on immunosuppressants. Participants must agree to use contraception if they can bear children.

Inclusion Criteria

Human immunodeficiency virus (HIV)-1/HIV-2 negative

All women of childbearing potential will have a pregnancy test and agree to use adequate contraception

Platelets >= 100,000/mm^3

Exclusion Criteria

Receiving other investigational agents

I am scheduled to receive certain vaccines around the time of the trial vaccination.

I have had genital warts in the past or currently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive RG1-VLP or saline placebo intramuscularly for 3 doses at months 0, 2, and 6. Blood and optional vaginal swab collections are conducted.

6 months

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including optional Gardasil-9 administration at months 12, 14, and 18.

6 months

3 visits (in-person)

Long-term follow-up

Participants are followed up to 6 months post-3rd RG1-VLP vaccination/saline injection or up to 14 days post-3rd Gardasil-9 vaccination.

6 months

What Are the Treatments Tested in This Trial?

Interventions

• RG1-VLP Vaccine

Trial Overview The trial tests a new vaccine called RG1-VLP against rare HPV types potentially causing cancer. It's compared with the approved Gardasil-9 vaccine. The study includes questionnaires, biospecimen collection, and uses saline as a control in some participants.

How Is the Trial Designed?

Group I: Prevention (RG1-VLP, Gardasil-9) Experimental Treatment 4 Interventions

Patients receive RG1-VLP IM for 3 doses at months 0, 2, and 6 in the absence of unacceptable toxicity. Patients may also receive Gardasil-9 via injection for 3 doses at 6 months after the 3rd study vaccination (month 12), then at months 14 and 18 in the absence of unacceptable toxicity. Patients also undergo blood sample collection on study and may undergo vaginal swab collection on study.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The RG2-VLP vaccine has been developed to provide broad-spectrum protection against both αHPVs, which cause anogenital and oropharyngeal cancers, and βHPVs associated with cutaneous squamous cell carcinoma, showing effectiveness in animal models.

In contrast to the Gardasil 9 vaccine, RG2-VLP induced strong immune responses against a wider range of HPV types, including those not covered by existing vaccines, suggesting its potential as a more comprehensive preventive measure against HPV-related cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RG2-VLP: a Vaccine Designed to Broadly Protect against Anogenital and Skin Human Papillomaviruses Causing Human Cancer. Olczak, P., Matsui, K., Wong, M., et al.[2023]

The RG1-VLP vaccine, which targets the HPV16 virus, demonstrated comparable efficacy to the licensed vaccine Cervarix in inducing neutralizing antibodies in rabbits, suggesting it could be an effective alternative for preventing HPV infections.

In mice, the RG1-VLP vaccine not only produced similar neutralization titers to Cervarix and Gardasil but also provided cross-protection against other high-risk HPV types, indicating its potential for broader protection against various HPV strains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incorporation of RG1 epitope into HPV16L1-VLP does not compromise L1-specific immunity. Schellenbacher, C., Huber, B., Skoll, M., et al.[2023]

The RG1-VLP vaccine, which targets the minor capsid protein L2 of HPV, induced strong immune responses and provided broad protection against a wide range of mucosal and cutaneous HPV types, including high-risk strains associated with cervical cancer.

Immunization with RG1-VLP resulted in long-lasting protection, demonstrated by effective defense against HPV challenges in mice even one year after vaccination, suggesting its potential as a next-generation vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of RG1-VLP vaccination against infections with genital and cutaneous human papillomaviruses. Schellenbacher, C., Kwak, K., Fink, D., et al.[2022]

Next-generation HPV vaccines, particularly those based on the minor structural protein L2, show promise for inducing broadly cross-type neutralizing antibodies, which could enhance protection against various HPV types beyond those included in current vaccines.

The RG1-VLP vaccine candidate, which presents a conserved neutralization epitope from HPV16 L2, has demonstrated cross-protection in animal studies against multiple high-risk and low-risk HPV types and is now ready for first-in-human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RG1-VLP and Other L2-Based, Broad-Spectrum HPV Vaccine Candidates. Huber, B., Wang, JW., Roden, RBS., et al.[2023]

The study developed chimeric virus-like particles (VLP) that incorporate RG1 epitopes from various HPV types, which significantly enhanced the immune response against beta HPV, suggesting a potential for broader protection against cutaneous HPV infections.

In animal models, these RG1-based VLPs demonstrated cross-protection against multiple beta HPV types, indicating their promise as next-generation vaccines for preventing skin warts and non-melanoma skin cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric L2-Based Virus-Like Particle (VLP) Vaccines Targeting Cutaneous Human Papillomaviruses (HPV). Huber, B., Schellenbacher, C., Shafti-Keramat, S., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05985681

Testing RG1-VLP Vaccine to Prevent HPV-related Cancers This trial may allow researchers to find out whether the RG1-VLP vaccine can safely trigger an immune response against HPV in healthy women and if it is better ...

2. 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% ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0022202X15360498

Efficacy of RG1-VLP Vaccination against Infections with ... RG1-VLP is a promising next-generation vaccine with broad efficacy against all relevant mucosal and also cutaneous HPV types.

4. withpower.com withpower.com/trial/phase-1-human-papilloma-virus-related-carcinoma-2024-68fec

RG1-VLP Vaccine for HPV-Related Cancers The RG1-VLP vaccine, which targets the HPV16 virus, demonstrated comparable efficacy to the licensed vaccine Cervarix in inducing neutralizing antibodies in ...

5. hpvworld.com hpvworld.com/articles/l2-based-human-papillomavirus-vaccines-current-status-and-potential/

L2-based Human Papillomavirus Vaccines: Current Status ... By targeting the seven most prevalent hrHPV detected in cancer, protection is expected against ~90% of cervical cancers (CaCx), leaving the remaining 10% ...

6. cancer.gov cancer.gov/clinicaltrials/NCI-2023-05780

Testing RG1-VLP Vaccine to Prevent HPV-related Cancers This phase I trial tests the safety, side effects, and best dose of RG1-virus-like particle (VLP) in preventing human papillomavirus (HPV)-related cancers ...

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

Human Papillomavirus (HPV) Vaccine Safety HPV vaccine is safe and effective at preventing HPV-related infections and cancers. Vaccines, like any medicine, can have side effects. Many ...