Neoplasms

All Conditions

Carcinoma

Pharmaceutical Solutions

All Drugs and Chemicals

Vaccines

Immunologic Factors

Patients receive RG1-VLP IM for 3 doses at months 0, 2, and 6 in the absence of disease progression or 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 disease progression or unacceptable toxicity. Patients also undergo blood sample collection on study and may undergo vaginal swab collection on study.

Patients receive saline placebo IM for 3 doses at months 0, 2, and 6 in the absence of disease progression or 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 disease progression or unacceptable toxicity. Patients also undergo blood sample collection on study and may undergo vaginal swab collection on study.

Undergo blood sample and vaginal swab collection

Biospecimen Collection

HPV16 RG1 VLP Vaccine

Questionnaire Administration

Recombinant Human Papillomavirus Nonavalent Vaccine

Saline

Warner K. Huh

Richard B. Roden

Mario R. Castellanos

Lisa M. Barroilhet

Reinhard Kirnbauer

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.

PRIMARY OBJECTIVE:

I. Assess the safety of RG1-virus-like particles (VLP) in healthy 18-45 years old women at 3 escalating doses.

SECONDARY OBJECTIVES:

I. Determine the immunogenicity of RG1-VLP in healthy 18-45 year old women at 3 escalating doses via the following assays:

Ia. Determine serum antibody responses induced by RG1-VLP vaccination by both human papillomavirus (HPV) 16 L1 VLP and HPV16 L2 RG1-peptide enzyme-linked immunosorbent assay (ELISA); Ib. Determine whether vaccination-induced serum antibody response neutralizes HPV16.

EXPLORATORY OBJECTIVES:

I. Determine whether vaccination-induced serum antibody response broadly neutralizes high risk (hr) HPV other than HPV16.

II. Determine whether vaccination induces a cell-mediated immune (CMI) response.

III. Determine whether vaccination-induced serum antibody response upon passive transfer to naive animals, protects mice against hrHPV pseudovirion (PsV) challenge.

IV. Determine whether vaccination results in changes in local antibody titers in vaginal and oral secretions (via oral rinse) and the effects of vaccination on HPV types in optionally-collected vaginal and oral secretions and eyebrow hair samples between months 0, 7 and 12.

V. Assess the safety of recombinant human papillomavirus nonavalent vaccine (Gardasil-9) in healthy women post-administration of RG1-VLP.

OUTLINE: This is a dose-escalation study of RG1-VLP. Patients are randomized to 1 of 2 arms.

ARM I: Patients receive RG1-VLP intramuscularly (IM) for 3 doses at months 0, 2, and 6 in the absence of disease progression or 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 disease progression or unacceptable toxicity. Patients also undergo blood sample collection on study and may undergo vaginal swab collection on study.

ARM II: Patients receive saline placebo IM for 3 doses at months 0, 2, and 6 in the absence of disease progression or 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 disease progression or unacceptable toxicity. Patients also undergo blood sample collection on study and may undergo vaginal swab collection on study.

Upon completion of study treatment, patients are followed up to 6 months post-3rd RG1-VLP vaccination/saline injection or up to 14 days post-3rd Gardasil-9 vaccination.

The study staff (excluding the pharmacist) and participants will be blinded to the vaccination arm.

Testing RG1-VLP Vaccine to Prevent HPV-related Cancers

A Dose Escalation Phase I Trial of the Safety and Immunogenicity of RG1-VLP, a Candidate Broadly Protective Vaccine for the Prevention of HPV-Associated Cancer

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

A dose response relationship with serum neutralizing antibody titer will be tested with linear mixed models or Jonckheere-Terpstra tests as appropriate.

Peripheral blood mononuclear cells will be isolated. There will be five mice for each human subject. The presence or absence of a vaccination serum antibody response will be recorded for each mouse. A dose-response relationship for serum antibody response will be tested with a repeated measures logistic regression analysis, accounting for the repetition of mice per subject.

There will be five mice for each human subject. The presence or absence of a vaccination serum antibody response will be recorded for each mouse. A dose-response relationship for serum antibody response will be tested with a repeated measures logistic regression analysis, accounting for the repetition of mice per subject.

These samples will be submitted for future research related to investigating local antibody responses and HPV deoxyribonucleic acid detection.

Safety of the three escalating doses of RG1-VLP will be assessed by adverse events in terms of severity grade and attribution to vaccination as ordinal outcomes. All toxicities will be tabulated and frequencies and percentages of events will be presented for each vaccine dose cohort. The severity of the adverse events will be assessed using the Common Terminology Criteria for Adverse Events 5.0 and supplemented by Food and Drug Administration "Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials."

Will be tested for IgG against HPV16 L1 using a VLP-based enzyme-linked immunosorbent assay (ELISA). The HPV16 L2 17-36 peptide will be synthesized and used for an L2 ELISA. A dose response relationship for log antibody response will be tested with a linear mixed model. Will be summarized with frequency and relative frequencies along with 95% confidence intervals by time, vaccine dose group, and visit. As appropriate, Jonckheere-Terpstra or Cochran-Armitage tests will be used to test for dose-response relationships.

In vitro HPV pseudovirion (PsV) neutralization assays will be performed for HPV16 and HPV18 and additional PsV types requested by the National Cancer Institute, using an assay specifically developed for sensitivity to L2-specific as well as L1-specific neutralizing antibodies. A dose response relationship with serum neutralizing antibody titer will be tested with linear mixed models or Jonckheere-Terpstra tests as appropriate. Will be summarized with frequency and relative frequencies along with 95% confidence intervals by time, vaccine dose group, and visit. As appropriate, Cochran-Armitage tests will be used to test for dose-response relationships.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Testing RG1-VLP Vaccine to Prevent HPV-related Cancers	NCT05985681	Human Papilloma...	Biospecimen Col... HPV16 RG1 VLP V... Questionnaire A... Recombinant Hum... Saline	18 Years - 45 Years	National Cancer Institute (NCI)
Testing RG1-VLP Vaccine to Prevent HPV-related Cancers	NCT05985681	Human Papilloma...	Biospecimen Col... HPV16 RG1 VLP V... Questionnaire A... Recombinant Hum... Saline	18 Years - 45 Years	National Cancer Institute (NCI)
Testing RG1-VLP Vaccine to Prevent HPV-related Cancers	NCT05985681	Human Papilloma...	Biospecimen Col... HPV16 RG1 VLP V... Questionnaire A... Recombinant Hum... Saline	18 Years - 45 Years	National Cancer Institute (NCI)
Testing RG1-VLP Vaccine to Prevent HPV-related Cancers	NCT05985681	Human Papilloma...	Biospecimen Col... HPV16 RG1 VLP V... Questionnaire A... Recombinant Hum... Saline	18 Years - 45 Years	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for hpv16 rg1 vlp vaccine