Wirkstoff:
HPV16 RG1 VLP Vaccine, Recombinant Human Papillomavirus Nonavalent Vaccine
Geschlecht:
Frauen
Altersgruppe:
Erwachsene (18+)
Phase:
Phase 1
Sponsor:
National Cancer Institute (NCI)
Collaborator:
-
Studienleiter
Reinhard Kirnbauer Principal Investigator Medical University of Vienna
Studienlocations (3 von 5)
University of Alabama at Birmingham Cancer Center 35233 Birmingham United States» Google-Maps Ansprechpartner: Warner K. Huh Phone: 205-934-9999 E-Mail: whuh@uabmc.edu» Ansprechpartner anzeigenJohns Hopkins University/Sidney Kimmel Cancer Center 21287 Baltimore United States» Google-Maps Ansprechpartner: Richard B. Roden Phone: 410-502-5161 E-Mail: roden@jhmi.edu» Ansprechpartner anzeigenStaten Island University Hospital 10305 Staten Island United States» Google-Maps Ansprechpartner: Mario R. Castellanos Phone: 718-226-6158 E-Mail: mcastellan@northwell.edu» Ansprechpartner anzeigen
University of Wisconsin Carbone Cancer Center 53792 Madison United States» Google-Maps Ansprechpartner: Lisa M. Barroilhet Phone: 608-265-2319 E-Mail: barroilhet@wisc.edu» Ansprechpartner anzeigenMedical University Vienna A-1090 Vienna Austria» Google-Maps Ansprechpartner: Reinhard Kirnbauer Phone: 43 1 40400 Ext. 77680 E-Mail: reinhard.kirnbauer@meduniwien.ac.at» Ansprechpartner anzeigen
1. Incidence of adverse events (Time Frame - Up to 6 months post-3rd RG1-virus-like particle (VLP) vaccination/saline injection): 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."
Secondary outcome:
1. Determination of serum antibody responses to both human papillomavirus (HPV)16 L1 VLP and to HPV16 L2 (Time Frame - At months 0, 1, 2, 3, 6, 7, and 12): 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.
2. Determination of whether vaccination-induced serum antibody response neutralizes HPV16 (Time Frame - At months 0, 1, 2, 3, 6, 7, and 12): 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.
Experimental: Arm I (RG1-VLP, Gardasil-9) Patients receive RG1-VLP IM for 3 doses at months 0, 2, and 6 in the absence of disease progression or 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 disease progression or unacceptable toxicity. Patients also undergo blood sample collection on study and may undergo vaginal swab collection on study.
Placebo Comparator: Arm II (saline placebo, Gardasil-9) Patients receive saline placebo IM for 3 doses at months 0, 2, and 6 in the absence of disease progression or 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 disease progression or unacceptable toxicity. Patients also undergo blood sample collection on study and may undergo vaginal swab collection on study.