Testing RG1-VLP Vaccine to Prevent HPV-related Cancers
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexFemale
Age18-60
SponsorNational Cancer Institute (NCI)
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Design model
Sequential
Treatments tested in this trial
Biospecimen Collection
Procedure/SurgeryUndergo blood sample and vaginal swab collection
HPV16 RG1 VLP Vaccine
Biological/VaccineGiven IM
Questionnaire Administration
Other interventionAncillary studies
Recombinant Human Papillomavirus Nonavalent Vaccine
Biological/VaccineGiven via injection
Treatment groups
18 Participants
are divided into 1 treatment groupGroup A: Prevention (RG1-VLP, Gardasil-9)Experimental treatment 4 interventions
Trial outcomes
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."
Time frame
Up to 6 months post-3rd RG1-virus-like particle (VLP) vaccination/saline injectionSecondary outcomes
1
Determination of serum antibody responses to both human papillomavirus (HPV)16 L1 VLP and to HPV16 L2
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.
Time frame
At months 0, 1, 2, 3, 6, 7, and 122
Determination of whether vaccination-induced serum antibody response neutralizes HPV16
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.
Time frame
At months 0, 1, 2, 3, 6, 7, and 12Other outcomes
1
Determination of whether vaccination-induced serum antibody response broadly neutralizes high-risk (hr)HPV other than HPV16
A dose response relationship with serum neutralizing antibody titer will be tested with linear mixed models or Jonckheere-Terpstra tests as appropriate.
Time frame
At months 0, 1, 2, 3, 6, 7 and 122
Determination of whether vaccination induces a cell-mediated immune response
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.
Time frame
At months 0, 1, and 73
Determination of whether vaccination-induced serum antibody response upon passive transfer to naive animals, protects mice against hrHPV pseudovirion challenge
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.
Time frame
At months 0 and 74
Determination of whether vaccination results in changes in 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
These samples will be submitted for future research related to investigating local antibody responses and HPV deoxyribonucleic acid detection.
Time frame
Between months 0, 7 and 12Sponsors and contacts
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Source ClinicalTrials.gov