xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05985681</url>
    </required_header>
    <id_info>
      <org_study_id>NCI-2023-05780</org_study_id>
      <secondary_id>NCI-2023-05780</secondary_id>
      <secondary_id>N01CN45009-45</secondary_id>
      <secondary_id>Pending19</secondary_id>
      <secondary_id>UWI20-04-01</secondary_id>
      <secondary_id>P30CA014520</secondary_id>
      <secondary_id>UG1CA242635</secondary_id>
      <nct_id>NCT05985681</nct_id>
    </id_info>
    <brief_title>Testing RG1-VLP Vaccine to Prevent HPV-related Cancers</brief_title>
    <official_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</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>National Cancer Institute (NCI)</agency>
        <agency_class>NIH</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>National Cancer Institute (NCI)</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        This phase I trial tests the safety, side effects, and best dose of RG1-virus-like particle&#xD;
        (VLP) in preventing human papillomavirus (HPV)-related cancers in women. RG1-VLP is a vaccine&#xD;
        that aims to protect against rare HPV types not targeted by currently approved HPV vaccines.&#xD;
        HPV is a common sexually-transmitted infection that can cause certain genital and oral&#xD;
        cancers. RG1-VLP contains a protein of HPV type 16 (HPV16) with a slightly different&#xD;
        structure than the licensed Gardasil-9 vaccine. Gardasil-9 is approved by the Federal Drug&#xD;
        Administration to help protect against diseases caused by some types of HPV. Gardasil-9 also&#xD;
        contains 9 different HPV proteins. Both vaccines contain alum to stimulate the immune system.&#xD;
        The usual approach for the prevention of HPV-related cancers for patients who are at&#xD;
        increased risk is to consider the currently approved HPV vaccine like Gardasil-9, as well as&#xD;
        to be followed closely by their doctor to watch for the development of cancer via routine pap&#xD;
        smears. This trial may allow researchers to find out whether the RG1-VLP vaccine can safely&#xD;
        trigger an immune response against HPV in healthy women and if it is better or worse than the&#xD;
        usual approach for the prevention of HPV-related cancers.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        PRIMARY OBJECTIVE:&#xD;
  &#xD;
        I. Assess the safety of RG1-virus-like particles (VLP) in healthy 18-45 years old women at 3&#xD;
        escalating doses.&#xD;
  &#xD;
        SECONDARY OBJECTIVES:&#xD;
  &#xD;
        I. Determine the immunogenicity of RG1-VLP in healthy 18-45 year old women at 3 escalating&#xD;
        doses via the following assays:&#xD;
  &#xD;
        Ia. Determine serum antibody responses induced by RG1-VLP vaccination by both human&#xD;
        papillomavirus (HPV) 16 L1 VLP and HPV16 L2 RG1-peptide enzyme-linked immunosorbent assay&#xD;
        (ELISA); Ib. Determine whether vaccination-induced serum antibody response neutralizes HPV16.&#xD;
  &#xD;
        EXPLORATORY OBJECTIVES:&#xD;
  &#xD;
        I. Determine whether vaccination-induced serum antibody response broadly neutralizes high&#xD;
        risk (hr) HPV other than HPV16.&#xD;
  &#xD;
        II. Determine whether vaccination induces a cell-mediated immune (CMI) response.&#xD;
  &#xD;
        III. Determine whether vaccination-induced serum antibody response upon passive transfer to&#xD;
        naive animals, protects mice against hrHPV pseudovirion (PsV) challenge.&#xD;
  &#xD;
        IV. Determine whether vaccination results in changes in local antibody titers in vaginal and&#xD;
        oral secretions (via oral rinse) and the effects of vaccination on HPV types in&#xD;
        optionally-collected vaginal and oral secretions and eyebrow hair samples between months 0, 7&#xD;
        and 12.&#xD;
  &#xD;
        V. Assess the safety of recombinant human papillomavirus nonavalent vaccine (Gardasil-9) in&#xD;
        healthy women post-administration of RG1-VLP.&#xD;
  &#xD;
        OUTLINE: This is a dose-escalation study of RG1-VLP. Patients are randomized to 1 of 2 arms.&#xD;
  &#xD;
        ARM I: Patients receive RG1-VLP intramuscularly (IM) for 3 doses at months 0, 2, and 6 in the&#xD;
        absence of disease progression or unacceptable toxicity. Patients may also receive Gardasil-9&#xD;
        via injection for 3 doses at 6 months after the 3rd study vaccination (month 12), then at&#xD;
        months 14 and 18 in the absence of disease progression or unacceptable toxicity. Patients&#xD;
        also undergo blood sample collection on study and may undergo vaginal swab collection on&#xD;
        study.&#xD;
  &#xD;
        ARM II: Patients receive saline placebo IM for 3 doses at months 0, 2, and 6 in the absence&#xD;
        of disease progression or unacceptable toxicity. Patients may also receive Gardasil-9 via&#xD;
        injection for 3 doses at 6 months after the 3rd saline injection (month 12), then at months&#xD;
        14 and 18 in the absence of disease progression or unacceptable toxicity. Patients also&#xD;
        undergo blood sample collection on study and may undergo vaginal swab collection on study.&#xD;
  &#xD;
        Upon completion of study treatment, patients are followed up to 6 months post-3rd RG1-VLP&#xD;
        vaccination/saline injection or up to 14 days post-3rd Gardasil-9 vaccination.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">January 15, 2024</start_date>
    <completion_date type="Anticipated">June 1, 2025</completion_date>
    <primary_completion_date type="Anticipated">June 1, 2025</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <primary_purpose>Prevention</primary_purpose>
      <masking>Double (Participant, Investigator)</masking>
      <masking_description>The study staff (excluding the pharmacist) and participants will be blinded to the vaccination arm.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Incidence of adverse events</measure>
      <time_frame>Up to 6 months post-3rd RG1-virus-like particle (VLP) vaccination/saline injection</time_frame>
      <description>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 &quot;Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials.&quot;</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Determination of serum antibody responses to both human papillomavirus (HPV)16 L1 VLP and to HPV16 L2</measure>
      <time_frame>At months 0, 1, 2, 3, 6, 7, and 12</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Determination of whether vaccination-induced serum antibody response neutralizes HPV16</measure>
      <time_frame>At months 0, 1, 2, 3, 6, 7, and 12</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Determination of whether vaccination-induced serum antibody response broadly neutralizes high-risk (hr)HPV other than HPV16</measure>
      <time_frame>At months 0, 1, 2, 3, 6, 7 and 12</time_frame>
      <description>A dose response relationship with serum neutralizing antibody titer will be tested with linear mixed models or Jonckheere-Terpstra tests as appropriate.</description>
    </other_outcome>
    <other_outcome>
      <measure>Determination of whether vaccination induces a cell-mediated immune response</measure>
      <time_frame>At months 0, 1, and 7</time_frame>
      <description>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.</description>
    </other_outcome>
    <other_outcome>
      <measure>Determination of whether vaccination-induced serum antibody response upon passive transfer to naive animals, protects mice against hrHPV pseudovirion challenge</measure>
      <time_frame>At months 0 and 7</time_frame>
      <description>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.</description>
    </other_outcome>
    <other_outcome>
      <measure>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</measure>
      <time_frame>Between months 0, 7 and 12</time_frame>
      <description>These samples will be submitted for future research related to investigating local antibody responses and HPV deoxyribonucleic acid detection.</description>
    </other_outcome>
    <other_outcome>
      <measure>Safety of administration of Gardasil-9 in individuals post-administration of RG1-VLP</measure>
      <time_frame>Up to 14 days post-3rd Gardasil-9 vaccination</time_frame>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">33</enrollment>
    <condition>Human Papillomavirus-Related Carcinoma</condition>
    <arm_group>
      <arm_group_label>Arm I (RG1-VLP, Gardasil-9)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>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.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Arm II (saline placebo, Gardasil-9)</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>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.</description>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Biospecimen Collection</intervention_name>
      <description>Undergo blood sample and vaginal swab collection</description>
      <arm_group_label>Arm I (RG1-VLP, Gardasil-9)</arm_group_label>
      <arm_group_label>Arm II (saline placebo, Gardasil-9)</arm_group_label>
      <other_name>Biological Sample Collection</other_name>
      <other_name>Biospecimen Collected</other_name>
      <other_name>Specimen Collection</other_name>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>HPV16 RG1 VLP Vaccine</intervention_name>
      <description>Given IM</description>
      <arm_group_label>Arm I (RG1-VLP, Gardasil-9)</arm_group_label>
      <other_name>16L1-16L2aa17-36-based Vaccine</other_name>
      <other_name>HPV16 RG1-VLP</other_name>
      <other_name>HPV16-RG1VLPs</other_name>
      <other_name>RG1-VLP Vaccine</other_name>
      <other_name>RG1-VLPs</other_name>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Questionnaire Administration</intervention_name>
      <description>Ancillary studies</description>
      <arm_group_label>Arm I (RG1-VLP, Gardasil-9)</arm_group_label>
      <arm_group_label>Arm II (saline placebo, Gardasil-9)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Recombinant Human Papillomavirus Nonavalent Vaccine</intervention_name>
      <description>Given via injection</description>
      <arm_group_label>Arm I (RG1-VLP, Gardasil-9)</arm_group_label>
      <arm_group_label>Arm II (saline placebo, Gardasil-9)</arm_group_label>
      <other_name>Gardasil 9</other_name>
      <other_name>Nonavalent HPV VLP Vaccine</other_name>
      <other_name>Recombinant HPV Nonavalent Vaccine</other_name>
      <other_name>Recombinant Human Papillomavirus 9-valent Vaccine</other_name>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Saline</intervention_name>
      <description>Given IM</description>
      <arm_group_label>Arm II (saline placebo, Gardasil-9)</arm_group_label>
      <other_name>ISOTONIC SODIUM CHLORIDE SOLUTION</other_name>
      <other_name>Normal Saline</other_name>
      <other_name>Sodium Chloride 0.9%</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Women, age 18 - 45 years. Because no dosing or adverse event (AE) data is currently&#xD;
               available for the use of RG1-VLP in humans, children and adolescents are excluded from&#xD;
               this study&#xD;
  &#xD;
            -  White blood cell (WBC) between 3000/mm^3-institutional upper limit of normal&#xD;
  &#xD;
            -  Hemoglobin (Hgb) between 10 g/dl-institutional upper limit of normal&#xD;
  &#xD;
            -  Platelets &gt;= 100,000/mm^3&#xD;
  &#xD;
            -  Serum creatinine within institutional normal limits&#xD;
  &#xD;
            -  Bilirubin =&lt; 2x institutional upper limit of normal&#xD;
  &#xD;
            -  Alanine aminotransferase (ALT) =&lt; 2x institutional upper limit of normal&#xD;
  &#xD;
            -  Aspartate aminotransferase (AST) =&lt; 2x institutional upper limit of normal&#xD;
  &#xD;
            -  Human immunodeficiency virus (HIV)-1/HIV-2 negative&#xD;
  &#xD;
            -  Hepatitis B and hepatitis C negative&#xD;
  &#xD;
            -  The effects of RG1-VLP vaccination on the developing human fetus at the proposed doses&#xD;
               are unknown. For this reason, all women of childbearing potential will have a&#xD;
               pregnancy test and all heterosexually active women must agree to use adequate&#xD;
               contraception (hormonal or barrier method of birth control; abstinence) prior to study&#xD;
               entry and for the duration of study participation. Should a woman become pregnant or&#xD;
               suspect she is pregnant while participating in this study, she should inform her study&#xD;
               physician immediately&#xD;
  &#xD;
            -  The following persons are not considered to be able to bear children and are therefore&#xD;
               eligible to participate without the use of concurrent birth control:&#xD;
  &#xD;
                 -  Female with bilateral oophorectomy and/or hysterectomy&#xD;
  &#xD;
                 -  Female with fallopian tubes cut, tied or sealed&#xD;
  &#xD;
                 -  Female with sterilization implant (e.g. Adiana, Essure) placed &gt; 3 months prior&#xD;
                    to randomization&#xD;
  &#xD;
                 -  Female post-menopausal (&gt; 1 year since last menses or prior laboratory follicle&#xD;
                    stimulating hormone (FSH) value per institutional range indicating&#xD;
                    post-menopausal)&#xD;
  &#xD;
            -  Eastern Cooperative Oncology Group (ECOG) performance status of =&lt; 1&#xD;
  &#xD;
            -  Ability to understand and the willingness to sign a written informed consent document&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  History of any of the following:&#xD;
  &#xD;
                 -  Prior or current genital warts&#xD;
  &#xD;
                 -  For women 25 and older: any abnormal Pap smear and positive HPV deoxyribonucleic&#xD;
                    acid (DNA) test (if co-testing), or positive HPV DNA test (if primary HPV&#xD;
                    screening)&#xD;
  &#xD;
                 -  Treatment for anogenital intraepithelial neoplasia (cervical intraepithelial&#xD;
                    neoplasia [CIN], anal intraepithelial neoplasia [AIN], vaginal intraepithelial&#xD;
                    neoplasia [VAIN], vulvar intraepithelial neoplasia [VIN])&#xD;
  &#xD;
                 -  Treatment for any cancer&#xD;
  &#xD;
            -  History of anaphylaxis to vaccines or fever &gt; 100 degrees Fahrenheit (F) within 72&#xD;
               hours of vaccination&#xD;
  &#xD;
            -  Any prior vaccination with Gardasil, Gardasil-9, or Cervarix or other HPV vaccine&#xD;
  &#xD;
            -  Receipt of blood products within 3 months of enrollment, or continuing plasma donation&#xD;
  &#xD;
            -  Participants receiving any other investigational agents&#xD;
  &#xD;
            -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
               composition to the adjuvant or to RG1-VLP&#xD;
  &#xD;
            -  Uncontrolled intercurrent illness or psychiatric illness/social situations that would&#xD;
               limit compliance with study requirements&#xD;
  &#xD;
            -  Pregnant women or actively lactating women are excluded from this study because&#xD;
               RG1-VLP is a vaccine with the potential for teratogenic or abortifacient effects&#xD;
  &#xD;
            -  Planned receipt of any inactivated vaccine in the 2 weeks preceding and the 2 weeks&#xD;
               following any trial vaccination&#xD;
  &#xD;
            -  Planned receipt of any live attenuated vaccine in the 4 weeks preceding and the 4&#xD;
               weeks following any trial vaccination&#xD;
  &#xD;
            -  Women with a history of bleeding disorders or use of anticoagulants (aspirin is&#xD;
               acceptable)&#xD;
  &#xD;
            -  Had prior medical conditions:&#xD;
  &#xD;
                 -  Rheumatoid arthritis or other auto-immune disease&#xD;
  &#xD;
                 -  Congenital or acquired immunodeficiency&#xD;
  &#xD;
                 -  Collagen vascular disease&#xD;
  &#xD;
            -  Following medical treatments:&#xD;
  &#xD;
                 -  Current use of immunosuppressive drugs including corticosteroid use (inhaled or&#xD;
                    topical steroids are permitted)&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>45 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Reinhard Kirnbauer</last_name>
      <role>Principal Investigator</role>
      <affiliation>Medical University of Vienna</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>University of Alabama at Birmingham Cancer Center</name>
        <address>
          <city>Birmingham</city>
          <state>Alabama</state>
          <zip>35233</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Warner K. Huh</last_name>
        <phone>205-934-9999</phone>
        <email>whuh@uabmc.edu</email>
      </contact>
      <investigator>
        <last_name>Warner K. Huh</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Johns Hopkins University/Sidney Kimmel Cancer Center</name>
        <address>
          <city>Baltimore</city>
          <state>Maryland</state>
          <zip>21287</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Richard B. Roden</last_name>
        <phone>410-502-5161</phone>
        <email>roden@jhmi.edu</email>
      </contact>
      <investigator>
        <last_name>Richard B. Roden</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Staten Island University Hospital</name>
        <address>
          <city>Staten Island</city>
          <state>New York</state>
          <zip>10305</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Mario R. Castellanos</last_name>
        <phone>718-226-6158</phone>
        <email>mcastellan@northwell.edu</email>
      </contact>
      <investigator>
        <last_name>Mario R. Castellanos</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>University of Wisconsin Carbone Cancer Center</name>
        <address>
          <city>Madison</city>
          <state>Wisconsin</state>
          <zip>53792</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Lisa M. Barroilhet</last_name>
        <phone>608-265-2319</phone>
        <email>barroilhet@wisc.edu</email>
      </contact>
      <investigator>
        <last_name>Lisa M. Barroilhet</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Medical University Vienna</name>
        <address>
          <city>Vienna</city>
          <zip>A-1090</zip>
          <country>Austria</country>
        </address>
      </facility>
      <contact>
        <last_name>Reinhard Kirnbauer</last_name>
        <phone>43 1 40400 Ext. 77680</phone>
        <email>reinhard.kirnbauer@meduniwien.ac.at</email>
      </contact>
      <investigator>
        <last_name>Reinhard Kirnbauer</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Austria</country>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 2, 2023</study_first_submitted>
    <study_first_submitted_qc>August 9, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>September 12, 2023</last_update_submitted>
    <last_update_submitted_qc>September 12, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Vaccines</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.</ipd_description>
      <ipd_url>https://grants.nih.gov/policy/sharing.htm</ipd_url>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05985681
  org study id: NCI-2023-05780
  secondary id: NCI-2023-05780
  secondary id: N01CN45009-45
  secondary id: Pending19
  secondary id: UWI20-04-01
  secondary id: P30CA014520
  secondary id: UG1CA242635
  nct id: NCT05985681
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: No
  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.
  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 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.
  
        ARM II: 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.
  
        Upon 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.
  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.
  measure: Incidence of adverse events
  time frame: Up to 6 months post-3rd RG1-virus-like particle (VLP) vaccination/saline injection
  description: 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."
  measure: 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
  description: 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.
  measure: Determination of whether vaccination-induced serum antibody response neutralizes HPV16
  time frame: At months 0, 1, 2, 3, 6, 7, and 12
  description: 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.
  measure: Determination of whether vaccination-induced serum antibody response broadly neutralizes high-risk (hr)HPV other than HPV16
  time frame: At months 0, 1, 2, 3, 6, 7 and 12
  description: A dose response relationship with serum neutralizing antibody titer will be tested with linear mixed models or Jonckheere-Terpstra tests as appropriate.
  measure: Determination of whether vaccination induces a cell-mediated immune response
  time frame: At months 0, 1, and 7
  description: 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.
  measure: Determination of whether vaccination-induced serum antibody response upon passive transfer to naive animals, protects mice against hrHPV pseudovirion challenge
  time frame: At months 0 and 7
  description: 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.
  measure: 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
  time frame: Between months 0, 7 and 12
  description: These samples will be submitted for future research related to investigating local antibody responses and HPV deoxyribonucleic acid detection.
  measure: Safety of administration of Gardasil-9 in individuals post-administration of RG1-VLP
  time frame: Up to 14 days post-3rd Gardasil-9 vaccination
  arm group label: Arm I (RG1-VLP, Gardasil-9)
  arm group type: Experimental
  description: 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.
  arm group label: Arm II (saline placebo, Gardasil-9)
  arm group type: Placebo Comparator
  description: 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.
  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%
  criteria: 
  gender: Female
  minimum age: 18 Years
  maximum age: 45 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Reinhard Kirnbauer
  role: Principal Investigator
  affiliation: Medical University of Vienna
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  country: Austria
  country: United States
  responsible party type: Sponsor
  mesh term: Vaccines
  sharing ipd: Yes
  ipd description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
  ipd url: https://grants.nih.gov/policy/sharing.htm