RG1-VLP Vaccine for HPV-Related Cancers

Recruiting at 5 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

Compensation: Varies

Number of Visits: 6

Duration: 6 months

33 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the RG1-VLP Vaccine treatment for HPV-related cancers?

Research shows that the RG1-VLP Vaccine can produce strong immune responses against a wide range of high-risk HPV types, similar to existing vaccines like Cervarix and Gardasil. It also offers cross-protection against other HPV types not covered by current vaccines, suggesting it could be effective in preventing various HPV-related cancers. ^{1 2 3 4 5}

Is the RG1-VLP vaccine safe for humans?

The RG1-VLP vaccine has been tested in animals and shown to induce immune responses similar to those of licensed vaccines, with no specific safety concerns reported in these studies. It is ready for a first-in-human clinical study, suggesting it has passed initial safety evaluations. ^{1 2 3 4 5}

How does the RG1-VLP vaccine differ from other treatments for HPV-related cancers?

The RG1-VLP vaccine is unique because it targets a broader range of HPV types, including both high-risk and low-risk types, as well as cutaneous HPV, by incorporating a conserved epitope from the minor capsid protein L2. This contrasts with existing vaccines that primarily target a limited number of HPV types using the major capsid protein L1. ^{1 2 3 4 5}

What is the purpose of this trial?

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 in women. RG1-VLP is a vaccine that aims to protect against rare HPV types not targeted by currently approved HPV vaccines. HPV is a common sexually-transmitted infection that can cause certain genital and oral cancers. RG1-VLP contains a protein of HPV type 16 (HPV16) with a slightly different structure than the licensed Gardasil-9 vaccine. Gardasil-9 is approved by the Federal Drug Administration to help protect against diseases caused by some types of HPV. Gardasil-9 also contains 9 different HPV proteins. Both vaccines contain alum to stimulate the immune system. The usual approach for the prevention of HPV-related cancers for patients who are at increased risk is to consider the currently approved HPV vaccine like Gardasil-9, as well as to be followed closely by their doctor to watch for the development of cancer via routine pap smears. 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 or worse than the usual approach for the prevention of HPV-related cancers.

Research Team

Reinhard Kirnbauer

Principal Investigator

Medical University of Vienna

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Arm I (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.

Group II: Arm II (saline placebo, Gardasil-9) Placebo Group 4 Interventions

Patients receive saline placebo 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 saline injection (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+

Findings from Research

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]

References

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

RG2-VLP: a Vaccine Designed to Broadly Protect against Anogenital and Skin Human Papillomaviruses Causing Human Cancer. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Incorporation of RG1 epitope into HPV16L1-VLP does not compromise L1-specific immunity. [2023]

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

Efficacy of RG1-VLP vaccination against infections with genital and cutaneous human papillomaviruses. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

RG1-VLP and Other L2-Based, Broad-Spectrum HPV Vaccine Candidates. [2023]

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

Chimeric L2-Based Virus-Like Particle (VLP) Vaccines Targeting Cutaneous Human Papillomaviruses (HPV). [2018]