Testing RG1-VLP Vaccine to Prevent HPV-related Cancers

PRIMARY OBJECTIVE:

I. Assess the safety of RG1-virus-like particles (VLP) in healthy 18-60 years old women at 3 escalating doses.

SECONDARY OBJECTIVES:

I. Determine the immunogenicity of RG1-VLP in healthy 18-60 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). This will be assessed at months 0, 1, 2, 3, 6, 7 and 12; Ib. Determine whether vaccination-induced serum antibody response neutralizes HPV16. This will be assessed at months 0, 1, 2, 3, 6, 7 and 12.

EXPLORATORY OBJECTIVES:

I. Determine whether vaccination-induced serum antibody response broadly neutralizes high risk (hr) HPV other than HPV16. This will be assessed at months 0, 1, 2, 3, 6, 7 and 12.

II. Determine whether vaccination induces a cell-mediated immune (CMI) response. Peripheral blood mononuclear cells (PBMC) will be isolated at months 0, 1 and 7.

III. Determine whether vaccination-induced serum antibody response upon passive transfer to naive animals, protects mice against hrHPV pseudovirion (PsV) challenge. This will be assessed at months 0 and 7.

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 receive RG1-VLP intramuscularly (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.

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

Inclusion criteria

• 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
• Female post-menopausal (> 1 year since last menses or prior laboratory follicle stimulating hormone [FSH] value per institutional range indicating post-menopausal)
• Eastern Cooperative Oncology Group (ECOG) performance status of =< 1
• Ability to understand and the willingness to sign a written informed consent document

Exclusion criteria

• 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:

• Rheumatoid arthritis or other auto-immune disease
• Congenital or acquired immunodeficiency
• Collagen vascular disease
• Following medical treatments:

• Current use of immunosuppressive drugs including corticosteroid use (inhaled or topical steroids are permitted)
• Unrecovered major infections and/or surgical procedures