Testing RG1-VLP Vaccine to Prevent HPV-related Cancers

NCT05985681 | Recruiting Phase 1 DMC FDA Drug

• 5 other identifiers: NCI-2023-05780N01CN45009-45UWI20-04-01P30CA014520UG1CA242635
• Study Type: interventional
• Target: 18
• Locations: 2 countries
• Sites: 5

Brief Summary

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.

Conditions

Human Papillomavirus-Related Carcinoma

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events

  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."

  Up to 6 months post-3rd RG1-virus-like particle (VLP) vaccination/saline injection

Secondary Outcomes (2)

• Determination of serum antibody responses to both human papillomavirus (HPV)16 L1 VLP and to HPV16 L2

  At months 0, 1, 2, 3, 6, 7, and 12

• Determination of whether vaccination-induced serum antibody response neutralizes HPV16

  At months 0, 1, 2, 3, 6, 7, and 12

Other Outcomes (5)

• Determination of whether vaccination-induced serum antibody response broadly neutralizes high-risk (hr)HPV other than HPV16

  At months 0, 1, 2, 3, 6, 7 and 12

• Determination of whether vaccination induces a cell-mediated immune response

  At months 0, 1, and 7

• Determination of whether vaccination-induced serum antibody response upon passive transfer to naive animals, protects mice against hrHPV pseudovirion challenge

  At months 0 and 7

Study Arms (1)

Prevention (RG1-VLP, Gardasil-9)

EXPERIMENTAL

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.

Procedure: Biospecimen Collection; Biological: HPV16 RG1 VLP Vaccine; Other: Questionnaire Administration; Biological: Recombinant Human Papillomavirus Nonavalent Vaccine

Interventions

Recombinant Human Papillomavirus Nonavalent Vaccine BIOLOGICAL

Given via injection

Also known as: Gardasil 9, Nonavalent HPV VLP Vaccine, Recombinant HPV Nonavalent Vaccine, Recombinant Human Papillomavirus 9-valent Vaccine

Prevention (RG1-VLP, Gardasil-9)

Biospecimen Collection PROCEDURE

Undergo blood sample and vaginal swab collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Prevention (RG1-VLP, Gardasil-9)

HPV16 RG1 VLP Vaccine BIOLOGICAL

Given IM

Also known as: 16L1-16L2aa17-36-based Vaccine, HPV16 RG1-VLP, HPV16-RG1VLPs, RG1-VLP Vaccine, RG1-VLPs

Prevention (RG1-VLP, Gardasil-9)

Questionnaire Administration OTHER

Ancillary studies

Prevention (RG1-VLP, Gardasil-9)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Women, age 18 - 60 years. Because no dosing or adverse event (AE) data is currently available for the use of RG1-VLP in humans, children and adolescents are excluded from this study
• White blood cell (WBC) between 3000/mm\^3 - institutional upper limit of normal
• Hemoglobin (Hgb) between 10 g/dl - institutional upper limit of normal
• Platelets \>= 100,000/mm\^3
• Serum creatinine within institutional normal limits
• Bilirubin =\< 2x institutional upper limit of normal
• Alanine aminotransferase (ALT) =\< 2x institutional upper limit of normal
• Aspartate aminotransferase (AST) =\< 2x institutional upper limit of normal
• Human immunodeficiency virus (HIV)-1/HIV-2 negative
• Hepatitis B and hepatitis C negative
• The effects of RG1-VLP vaccination on the developing human fetus at the proposed doses are unknown. For this reason, all women of childbearing potential will have a pregnancy test and all heterosexually active women must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
• The following persons are not considered to be able to bear children and are therefore eligible to participate without the use of concurrent birth control:
• Female with bilateral oophorectomy and/or hysterectomy
• Female with fallopian tubes cut, tied or sealed
• Female with sterilization implant (e.g. Adiana, Essure) placed \> 3 months prior to randomization

You may not qualify if:

• History of any of the following:
• Prior or current genital warts
• Treatment for anogenital intraepithelial neoplasia (cervical intraepithelial neoplasia \[CIN\], anal intraepithelial neoplasia \[AIN\], vaginal intraepithelial neoplasia \[VAIN\], vulvar intraepithelial neoplasia \[VIN\])
• Systemic cancer treatment within the prior year
• History of anaphylaxis to vaccines
• Any prior vaccination with Gardasil, Gardasil-9, or Cervarix or other HPV vaccine
• Receipt of blood products within 3 months of enrollment, or continuing plasma donation
• Participants receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to the adjuvant or to RG1-VLP
• Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements or preclude protocol vaccination
• Pregnant women or actively lactating women are excluded from this study because RG1-VLP is a vaccine with the potential for teratogenic or abortifacient effects
• Planned receipt of any inactivated vaccine in the 2 weeks preceding and the 2 weeks following any trial vaccination
• Planned receipt of any live attenuated vaccine in the 4 weeks preceding and the 4 weeks following any trial vaccination
• Women with a history of bleeding disorders or use of anticoagulants (aspirin is acceptable)
• Had prior medical diagnoses:

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (5)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

WITHDRAWN

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

WITHDRAWN

Staten Island University Hospital

Staten Island, New York, 10305, United States

WITHDRAWN

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792, United States

RECRUITING

Medical University Vienna

Vienna, A-1090, Austria

NOT YET RECRUITING

MeSH Terms

Interventions

Specimen Handling; Human Papillomavirus Recombinant Vaccine nonavalent

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Reinhard Kirnbauer

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2023
• First Posted: August 14, 2023
• Study Start: February 27, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

AU (1); US (4)