Trial Title:
Testing RG1-VLP Vaccine to Prevent HPV-related Cancers
NCT ID:
NCT05985681
Condition:
Human Papillomavirus-Related Carcinoma
Conditions: Official terms:
Vaccines
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Prevention
Masking:
Double (Participant, Investigator)
Masking description:
The study staff (excluding the pharmacist) and participants will be blinded to the
vaccination arm.
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample and vaginal swab collection
Arm group label:
Arm I (RG1-VLP, Gardasil-9)
Arm group label:
Arm II (saline placebo, Gardasil-9)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Biological
Intervention name:
HPV16 RG1 VLP Vaccine
Description:
Given IM
Arm group label:
Arm I (RG1-VLP, Gardasil-9)
Other name:
16L1-16L2aa17-36-based Vaccine
Other name:
HPV16 RG1-VLP
Other name:
HPV16-RG1VLPs
Other name:
RG1-VLP Vaccine
Other name:
RG1-VLPs
Intervention type:
Other
Intervention name:
Questionnaire Administration
Description:
Ancillary studies
Arm group label:
Arm I (RG1-VLP, Gardasil-9)
Arm group label:
Arm II (saline placebo, Gardasil-9)
Intervention type:
Biological
Intervention name:
Recombinant Human Papillomavirus Nonavalent Vaccine
Description:
Given via injection
Arm group label:
Arm I (RG1-VLP, Gardasil-9)
Arm group label:
Arm II (saline placebo, Gardasil-9)
Other name:
Gardasil 9
Other name:
Nonavalent HPV VLP Vaccine
Other name:
Recombinant HPV Nonavalent Vaccine
Other name:
Recombinant Human Papillomavirus 9-valent Vaccine
Intervention type:
Other
Intervention name:
Saline
Description:
Given IM
Arm group label:
Arm II (saline placebo, Gardasil-9)
Other name:
ISOTONIC SODIUM CHLORIDE SOLUTION
Other name:
Normal Saline
Other name:
Sodium Chloride 0.9%
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.
Detailed description:
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 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.
After 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.
Criteria for eligibility:
Criteria:
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
Exclusion Criteria:
- History of any of the following:
- Prior or current genital warts
- For women 25 and older: any abnormal Pap smear and positive HPV
deoxyribonucleic acid (DNA) test (if co-testing), or positive HPV DNA test (if
primary HPV screening)
- Treatment for anogenital intraepithelial neoplasia (cervical intraepithelial
neoplasia [CIN], anal intraepithelial neoplasia [AIN], vaginal intraepithelial
neoplasia [VAIN], vulvar intraepithelial neoplasia [VIN])
- Treatment for any cancer
- History of anaphylaxis to vaccines or fever > 100 degrees Fahrenheit (F) within 72
hours of vaccination
- 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
- 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 conditions:
- 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)
Gender:
Female
Minimum age:
18 Years
Maximum age:
45 Years
Healthy volunteers:
Accepts Healthy Volunteers
Locations:
Facility:
Name:
University of Alabama at Birmingham Cancer Center
Address:
City:
Birmingham
Zip:
35233
Country:
United States
Contact:
Last name:
Warner K. Huh
Phone:
205-934-9999
Email:
whuh@uabmc.edu
Investigator:
Last name:
Warner K. Huh
Email:
Principal Investigator
Facility:
Name:
Johns Hopkins University/Sidney Kimmel Cancer Center
Address:
City:
Baltimore
Zip:
21287
Country:
United States
Contact:
Last name:
Richard B. Roden
Phone:
410-502-5161
Email:
roden@jhmi.edu
Investigator:
Last name:
Richard B. Roden
Email:
Principal Investigator
Facility:
Name:
Staten Island University Hospital
Address:
City:
Staten Island
Zip:
10305
Country:
United States
Contact:
Last name:
Mario R. Castellanos
Phone:
718-226-6158
Email:
mcastellan@northwell.edu
Investigator:
Last name:
Mario R. Castellanos
Email:
Principal Investigator
Facility:
Name:
University of Wisconsin Carbone Cancer Center - University Hospital
Address:
City:
Madison
Zip:
53792
Country:
United States
Contact:
Last name:
Lisa M. Barroilhet
Phone:
608-265-2319
Email:
barroilhet@wisc.edu
Investigator:
Last name:
Lisa M. Barroilhet
Email:
Principal Investigator
Facility:
Name:
Medical University Vienna
Address:
City:
Vienna
Zip:
A-1090
Country:
Austria
Contact:
Last name:
Reinhard Kirnbauer
Phone:
43 1 40400 Ext. 77680
Email:
reinhard.kirnbauer@meduniwien.ac.at
Investigator:
Last name:
Reinhard Kirnbauer
Email:
Principal Investigator
Start date:
April 13, 2025
Completion date:
June 1, 2027
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05985681
