Title
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

Description
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.

Objective
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.

Treatment 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 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.

ARM II: 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.

Key Eligibility Inclusion Criteria:

Women, age 18 - 45 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

Applicable Disease Sites
Anal; Cervix; Head and Neck; Ovary

Participating Institutions
UW - Madison; UW Health 20 S. Park; UW Health Eastpark Medical Center