<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/NCT03036930</url>
  </required_header>
  <id_info>
    <org_study_id>NCI-2017-00116</org_study_id>
    <secondary_id>NCI-2017-00116</secondary_id>
    <secondary_id>N01-CN-2012-00035</secondary_id>
    <secondary_id>NCI2015-06-02</secondary_id>
    <secondary_id>NWU2015-06-02</secondary_id>
    <secondary_id>N01CN00035</secondary_id>
    <secondary_id>P30CA060553</secondary_id>
    <nct_id>NCT03036930</nct_id>
  </id_info>
  <brief_title>Preventive Human Papillomavirus (HPV) Vaccine Trial in Kidney Transplant Recipients</brief_title>
  <official_title>Immunogenicity of Nonavalent HPV Vaccine Administered Prior to Renal Transplantation in Adults: A Prospective, Single-Arm, Multi-Center Clinical Trial</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial studies whether the nonavalent human papillomavirus vaccine given to&#xD;
      adults prior to kidney transplantation can help the body build and maintain an effective&#xD;
      immune response during the post-transplant period when they receive immunosuppressive drugs&#xD;
      to prevent transplant rejection. This study will help inform our scientific understanding&#xD;
      about vaccine-induced immune responses among immunosuppressed individuals.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To assess human papillomavirus (HPV) vaccine-type-specific seroconversion rates at&#xD;
      12-months post-transplantation among kidney transplant recipients who receive &gt;= 1 doses of&#xD;
      the recombinant human papillomavirus nonavalent vaccine (Gardasil [registered trademark] 9&#xD;
      HPV vaccine) &gt;= 30 days prior to transplantation.&#xD;
&#xD;
      SECONDARY OBJECTIVE:&#xD;
&#xD;
      I. To assess HPV vaccine-type-specific seroconversion rates at 6- and 12-months&#xD;
      post-transplantation stratified by number of doses (1, 2, or 3) of the vaccine given&#xD;
      pre-transplant among kidney transplant recipients who receive &gt;= 1 doses of the Gardasil 9&#xD;
      HPV vaccine prior to transplantation.&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. To assess the following among kidney transplant recipients who receive &gt;= 1 doses of the&#xD;
      Gardasil 9 HPV vaccine &gt;= 30 days prior to transplantation:&#xD;
&#xD;
      Ia. HPV vaccine-type-specific seroconversion rates at 12-months post-transplantation&#xD;
      stratified by:&#xD;
&#xD;
      Ii. Time elapsed between last vaccine dose and the transplant procedure; Iii. Variations in&#xD;
      dosing and types of post-transplant immunosuppressant medications; and interactions with type&#xD;
      of transplant surgery (living donor/deceased donor); Iiii. Differences in human leukocyte&#xD;
      antigen (HLA) histocompatibility between donor and recipient; Iiv. Differences in biological&#xD;
      sex (i.e. male versus [vs.] female) of the transplant recipient; Ib. Stability of HPV&#xD;
      vaccine-type-specific geometric mean titers (GMT) at 6 and 12-months post-transplantation and&#xD;
      rise in HPV vaccine-type-specific GMT at the 13-month post-transplant visit; Ic. Vaccine&#xD;
      safety profile and allograft rejection/opportunistic infections stratified by number of&#xD;
      vaccine doses and time between the last vaccine dose and the transplant procedure; Id. HPV&#xD;
      detection in samples from the cervix/vagina and oral cavity at baseline (pre-vaccination) and&#xD;
      at 6- and 12-months post-vaccination, overall and by number of vaccine doses (1, 2, or 3),&#xD;
      sexual behavior, type-specific seroconversion rates, and time elapsed between the last&#xD;
      vaccine dose and the transplant procedure.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Participants receive the first dose of the recombinant human papillomavirus nonavalent&#xD;
      vaccine intramuscularly (IM) at baseline, at least 30 days prior to the kidney transplant&#xD;
      surgery. The second dose is given at least one month after the first dose. The third dose is&#xD;
      given at least five months after the first dose and at least three months after the second&#xD;
      dose. The timing of the second and third doses is dependent on the scheduling of the kidney&#xD;
      transplant surgery. Patients are followed up at 6- and 12-months after the kidney transplant&#xD;
      surgery to measure vaccine-induced immune responses. Patients may receive either one, two, or&#xD;
      all three vaccine doses prior to the kidney transplant surgery, and are offered additional&#xD;
      visits at least one year after the surgery to complete any remaining doses of the three-dose&#xD;
      vaccine series. Patients also undergo collection of blood samples and self-collection of&#xD;
      cervical/vaginal samples (female participants only) on study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 23, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Human papillomavirus (HPV) vaccine-type-specific seroconversion rates among kidney transplant recipients who receive &gt;= 1 doses of the vaccine &gt;= 30 days prior to transplantation</measure>
    <time_frame>At 12 months post-transplant</time_frame>
    <description>An estimate of the seroconversion rate will be provided along with exact Clopper-Pearson 95% confidence intervals (CIs).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>HPV vaccine-type-specific seroconversion rates</measure>
    <time_frame>At 6 and 12 months post-transplant</time_frame>
    <description>Descriptive statistics, such as probabilities and exact 95% CIs, will be used to summarize HPV vaccine-type-specific seroconversion rates at 6- and 12-months post-transplantation stratified by number of doses (1, 2, or 3) of the vaccine given pre-transplant. Seroconversion probabilities will be compared between dose groups using Fisher's exact test. Armitage trend test will be used to examine whether there is a trend for increased seropositivity across dose groups.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Probability of seroconversion</measure>
    <time_frame>At 12 months post-transplant</time_frame>
    <description>Descriptive statistics, such as probabilities and exact 95% CIs, will be used to summarize probability of seroconversion at 12 months post-transplant for the following groups: a) time elapsed between last vaccine dose and the transplant procedure, e.g. &lt; 3 months versus (vs.) &gt; 3 months. Different groupings will be considered based on observed (e.g. median) and clinical considerations. Time will be summarized using descriptive statistics, e.g. median, interquartile range, or range; groups defined by dosing and types of post-transplant immunosuppressant medications, as well as; b) type of transplant surgery (living donor/deceased donor); c) differences in human leukocyte antigen histocompatibility between donor and recipient; d) differences by biological sex (i.e., male vs. female) of the transplant recipient.</description>
  </other_outcome>
  <other_outcome>
    <measure>Stability of HPV vaccine-type-specific geometric mean titers (GMT)</measure>
    <time_frame>At 6 and 12 months post-transplant</time_frame>
    <description>Stability will be evaluated in relation to changes in the type-specific GMTs between the two post-transplant time points (6- and 12-months post-transplant) and reported as follows: (i) decrease: more than 2-fold decrease, (ii) stable: within 2-fold change, and (iii) increase: greater than 2-fold increase. Stability will also be described in relation to the number of vaccine doses (1, 2 or 3) received in the pre-transplant period.</description>
  </other_outcome>
  <other_outcome>
    <measure>Rise in HPV vaccine-type-specific GMT</measure>
    <time_frame>At 13 months post-transplant</time_frame>
    <description>The magnitude of increase in type-specific GMTs at the 13-month post-transplant visit (i.e., 1 month after the booster dose) will be described in relation to the type-specific GMTs at the other post-transplant visits (6 and 12-months post -transplant). Patterns over time will also be explored using graphical techniques. Post-booster dose increase in type-specific GMTs will also be described in relation to the number of vaccine doses (1, 2 or 3) received in the pre-transplant period.</description>
  </other_outcome>
  <other_outcome>
    <measure>Vaccine safety profile and allograft rejection/opportunistic infections</measure>
    <time_frame>Up to 13 months post-transplant</time_frame>
    <description>Will be summarized using descriptive statistics, stratified by number of vaccine doses and time between the last vaccine dose and the transplant procedure.</description>
  </other_outcome>
  <other_outcome>
    <measure>HPV detection in samples from the cervix/vagina, and oral cavity</measure>
    <time_frame>Self-collected at baseline (pre-vaccination) and at 6- and 12- months post-vaccination</time_frame>
    <description>HPV detection in samples from the cervix/vagina, and oral cavity at baseline (pre-vaccination) and at 6- and 12-months post-vaccination, overall and by number of vaccine doses (1, 2, or 3), sexual behavior, type-specific seroconversion rates, and time elapsed between the last vaccine dose and the transplant procedure will be evaluated. All rates of HPV detection will be specified, overall and stratified by number of doses (1, 2, or 3) and time to transplant.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">180</enrollment>
  <condition>Human Papillomavirus Infection</condition>
  <arm_group>
    <arm_group_label>Prevention (Gardasil 9 HPV vaccine)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive the first dose of the recombinant human papillomavirus nonavalent vaccine IM at baseline, at least 30 days prior to the kidney transplant surgery. The second dose is given at least one month after the first dose. The third dose is given at least five months after the first dose and at least three months after the second dose. The timing of the second and third doses is dependent on the scheduling of the kidney transplant surgery. Patients are followed up at 6- and 12-months after the kidney transplant surgery to measure vaccine-induced immune responses. Patients may receive either one, two, or all three vaccine doses prior to the kidney transplant surgery, and are offered additional visits at least one year after the surgery to complete any remaining doses of the three-dose vaccine series. Patients also undergo collection of blood samples and self-collection of cervical/vaginal samples (female participants only) on study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Biospecimen Collection</intervention_name>
    <description>Undergo collection of blood samples</description>
    <arm_group_label>Prevention (Gardasil 9 HPV vaccine)</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>Procedure</intervention_type>
    <intervention_name>HPV Self-Collection</intervention_name>
    <description>Undergo self-collection of vaginal/cervical samples</description>
    <arm_group_label>Prevention (Gardasil 9 HPV vaccine)</arm_group_label>
    <other_name>At-home HPV Self Collection</other_name>
    <other_name>HPV Self Collection</other_name>
    <other_name>Human Papillomavirus Self-Collection</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Questionnaire Administration</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Prevention (Gardasil 9 HPV vaccine)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Recombinant Human Papillomavirus Nonavalent Vaccine</intervention_name>
    <description>Given IM</description>
    <arm_group_label>Prevention (Gardasil 9 HPV vaccine)</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>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Candidate for renal transplant, expected to undergo transplant surgery &gt;= 30 days and&#xD;
             =&lt; 12 months after enrollment&#xD;
&#xD;
               -  For potential participants on the institutional waiting list for deceased donor&#xD;
                  transplant, a study clinician confirms the candidate is likely to receive a&#xD;
                  transplant within the next 12 months, taking into account the candidate's&#xD;
                  priority on the waiting list, age, medical status, institutional policies, and&#xD;
                  scores like the Estimated Post-Transplant Survival (EPTS) Score and Calculated&#xD;
                  Panel Reactive Antibody (CPRA) percentage, etc&#xD;
&#xD;
               -  For potential participants expected to undergo a living donor transplant, one or&#xD;
                  more donor(s) have been identified and is/are in work-up (even though all work-up&#xD;
                  status may or may not be complete); a study clinician confirms the living donor&#xD;
                  transplant is likely to be scheduled within the next twelve months after taking&#xD;
                  into account donor work-up progress, age and medical status, and institutional&#xD;
                  policies&#xD;
&#xD;
               -  Notes:&#xD;
&#xD;
                    -  Living and deceased donor transplant recipients: The study was originally&#xD;
                       restricted to participants who were expecting to receive only living donor&#xD;
                       renal transplants; however, less than a third of kidney transplants in the&#xD;
                       United States occur with kidneys from living donors; a majority of&#xD;
                       transplants are in the setting of donation of kidneys from deceased donors;&#xD;
                       to permit efficiencies in accrual, the study is amended (from version 3.5)&#xD;
                       to also open enrollment to recipients of deceased donor kidneys&#xD;
&#xD;
                    -  Transplant recipients of both genders: The study was originally designed to&#xD;
                       be conducted only among women; however, in October 2018, the Food and Drug&#xD;
                       Administration (FDA) approved an age expansion indication for the Gardasil 9&#xD;
                       HPV vaccine for both women and men up to 45 years (from the originally&#xD;
                       approved upper age limit of 26 years), thus opening a new clinical cancer&#xD;
                       preventative option for middle-age adults of both genders; the primary&#xD;
                       endpoint for the study is HPV-vaccine-type-specific seroconversion rates,&#xD;
                       which are not expected to be differential by gender, based on extrapolating&#xD;
                       from the uniformly high (&gt; 99%) seroconversion rates observed regardless of&#xD;
                       gender in studies among immunocompetent individuals; however, HPV&#xD;
                       vaccine-type-specific titer levels (GMT) differences by gender will be&#xD;
                       analyzed as a secondary endpoint, given variability in immune response titer&#xD;
                       levels observed between males and females in immunocompetent individuals&#xD;
                       (related to the differences in body mass index or hitherto unproven factors&#xD;
                       related to hormone-immune interactions); another advantage of expanding this&#xD;
                       study to males will be to facilitate efficiencies in accrual, since men&#xD;
                       constitute the majority (55%-65%) of all kidney transplant recipients in the&#xD;
                       United States; although a majority of current HPV-associated cancers among&#xD;
                       solid organ transplant recipients occur among women, there is increasing&#xD;
                       evidence of the link between HPV infection and oropharyngeal cancers that&#xD;
                       disproportionately affect men; HPV-related oropharyngeal cancers are now the&#xD;
                       most common HPV-related cancers in the United States, surpassing even the&#xD;
                       incidence of cervical cancer; the expansion of enrollment to men will also&#xD;
                       allow this study to look at the effect of HPV vaccination on persistence of&#xD;
                       oral HPV infection as a secondary/exploratory endpoint in the context of&#xD;
                       transplant-related immunosuppression&#xD;
&#xD;
          -  Age 18-49 years. We have chosen to focus on adults aged 18-49 for this initial study&#xD;
             in transplant recipients for a few reasons. Prior data for HPV vaccine response exists&#xD;
             for adults up to 49 years of age, providing an important external comparison group for&#xD;
             our study. Immune response and exposure wane as age increases and we want to minimize&#xD;
             the potential for age-related confounding of our study outcome. For this initial&#xD;
             trial, we thought it best to maintain homogeneity in the study population to the&#xD;
             extent possible. Finally, given that about half of renal transplant recipients in the&#xD;
             United States (U.S.) are between the ages of 18-49 years, selecting this age range&#xD;
             permits efficiency in study accrual&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status =&lt; 1 (Karnofsky &gt;= 70%)&#xD;
&#xD;
          -  The effects of the Gardasil 9 HPV vaccine on the developing human fetus at the&#xD;
             recommended therapeutic dose are unknown; for this reason and because there have been&#xD;
             no adequate and well-controlled studies of Gardasil 9 in pregnant women, women who are&#xD;
             able to become pregnant must have a confirmed negative pregnancy test result within&#xD;
             the past 28 days prior to enrollment and must agree to use adequate contraception&#xD;
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for&#xD;
             the duration of study participation; women who have had a both ovaries removed or a&#xD;
             tubal ligation will not be required to have a pregnancy test; should a woman become&#xD;
             pregnant or suspect she is pregnant while participating in this study, she should&#xD;
             inform her study physician immediately&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
             and medical release form&#xD;
&#xD;
          -  Willing and able to comply with trial protocol and follow-up&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous prophylactic HPV vaccination&#xD;
&#xD;
          -  Prior organ transplant&#xD;
&#xD;
          -  Anticipated desensitization treatment; this decision to exclude a participant who may&#xD;
             need desensitization will be based on the site clinician's judgement; desensitization&#xD;
             procedures vary somewhat among the five participating transplant centers, which does&#xD;
             not permit proposing uniform criteria across all study sites for determining exclusion&#xD;
             due to desensitization; in general, women who have received a prior transplant, have&#xD;
             unsuitable scores on Calculated Panel Reactive Antibody (PRA) percentage&#xD;
             (institution-specific thresholds), or an ABO incompatible donor are likely to undergo&#xD;
             desensitization at one or more of the study centers; these factors, among others, will&#xD;
             be used by the study clinician to determine exclusion due to anticipated&#xD;
             desensitization is warranted for a particular participant in the study&#xD;
&#xD;
          -  Current use of any other investigational agents&#xD;
&#xD;
          -  History of allergic reactions to yeast or attributed to compounds of similar chemical&#xD;
             or biologic composition to Gardasil 9 HPV vaccine&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements&#xD;
&#xD;
          -  For female participants: Pregnant or intention to get pregnant, or breastfeeding;&#xD;
             pregnant women are excluded from this study because the safety and effectiveness of&#xD;
             Gardasil 9 HPV vaccine have not been established in pregnant women; it is not known&#xD;
             whether Gardasil 9 is excreted in human milk; because many drugs are excreted in human&#xD;
             milk, caution should be exercised when Gardasil 9 is administered to a nursing woman;&#xD;
             because there is an unknown but potential risk for adverse events in nursing infants&#xD;
             secondary to treatment of the mother with Gardasil 9, women who are breastfeeding will&#xD;
             be excluded&#xD;
&#xD;
          -  History of cervical cancer or anal cancer&#xD;
&#xD;
          -  History of active malignancy, including basal/squamous cell skin cancer&#xD;
&#xD;
          -  Concurrent illness, such as known psychiatric disorders or substance abuse (i.e.,&#xD;
             average alcohol consumption of more than 3 drinks per day), which in the opinion of&#xD;
             the investigators would compromise either the patient or the integrity of the data&#xD;
&#xD;
          -  Patients on anticoagulation or with bleeding disorders should be evaluated by a&#xD;
             physician for risk/benefit of bleeding disorders with intramuscular injections prior&#xD;
             to study enrollment; patients determined to be at high risk for bleeding with&#xD;
             intramuscular injections will be excluded&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>49 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marc T Goodman</last_name>
    <role>Principal Investigator</role>
    <affiliation>Northwestern University</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>
  </location>
  <location>
    <facility>
      <name>Cedars Sinai Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90048</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCSF Medical Center-Mount Zion</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic in Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UNC Lineberger Comprehensive Cancer Center</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>January 30, 2017</study_first_submitted>
  <study_first_submitted_qc>January 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 31, 2017</study_first_posted>
  <last_update_submitted>July 21, 2023</last_update_submitted>
  <last_update_submitted_qc>July 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 24, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Papillomavirus Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vaccines</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT03036930
org study id: NCI-2017-00116
secondary id: NCI-2017-00116
secondary id: N01-CN-2012-00035
secondary id: NCI2015-06-02
secondary id: NWU2015-06-02
secondary id: N01CN00035
secondary id: P30CA060553
nct id: NCT03036930
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies whether the nonavalent human papillomavirus vaccine given to
      adults prior to kidney transplantation can help the body build and maintain an effective
      immune response during the post-transplant period when they receive immunosuppressive drugs
      to prevent transplant rejection. This study will help inform our scientific understanding
      about vaccine-induced immune responses among immunosuppressed individuals.
PRIMARY OBJECTIVE:

      I. To assess human papillomavirus (HPV) vaccine-type-specific seroconversion rates at
      12-months post-transplantation among kidney transplant recipients who receive >= 1 doses of
      the recombinant human papillomavirus nonavalent vaccine (Gardasil [registered trademark] 9
      HPV vaccine) >= 30 days prior to transplantation.

      SECONDARY OBJECTIVE:

      I. To assess HPV vaccine-type-specific seroconversion rates at 6- and 12-months
      post-transplantation stratified by number of doses (1, 2, or 3) of the vaccine given
      pre-transplant among kidney transplant recipients who receive >= 1 doses of the Gardasil 9
      HPV vaccine prior to transplantation.

      EXPLORATORY OBJECTIVES:

      I. To assess the following among kidney transplant recipients who receive >= 1 doses of the
      Gardasil 9 HPV vaccine >= 30 days prior to transplantation:

      Ia. HPV vaccine-type-specific seroconversion rates at 12-months post-transplantation
      stratified by:

      Ii. Time elapsed between last vaccine dose and the transplant procedure; Iii. Variations in
      dosing and types of post-transplant immunosuppressant medications; and interactions with type
      of transplant surgery (living donor/deceased donor); Iiii. Differences in human leukocyte
      antigen (HLA) histocompatibility between donor and recipient; Iiv. Differences in biological
      sex (i.e. male versus [vs.] female) of the transplant recipient; Ib. Stability of HPV
      vaccine-type-specific geometric mean titers (GMT) at 6 and 12-months post-transplantation and
      rise in HPV vaccine-type-specific GMT at the 13-month post-transplant visit; Ic. Vaccine
      safety profile and allograft rejection/opportunistic infections stratified by number of
      vaccine doses and time between the last vaccine dose and the transplant procedure; Id. HPV
      detection in samples from the cervix/vagina and oral cavity at baseline (pre-vaccination) and
      at 6- and 12-months post-vaccination, overall and by number of vaccine doses (1, 2, or 3),
      sexual behavior, type-specific seroconversion rates, and time elapsed between the last
      vaccine dose and the transplant procedure.

      OUTLINE:

      Participants receive the first dose of the recombinant human papillomavirus nonavalent
      vaccine intramuscularly (IM) at baseline, at least 30 days prior to the kidney transplant
      surgery. The second dose is given at least one month after the first dose. The third dose is
      given at least five months after the first dose and at least three months after the second
      dose. The timing of the second and third doses is dependent on the scheduling of the kidney
      transplant surgery. Patients are followed up at 6- and 12-months after the kidney transplant
      surgery to measure vaccine-induced immune responses. Patients may receive either one, two, or
      all three vaccine doses prior to the kidney transplant surgery, and are offered additional
      visits at least one year after the surgery to complete any remaining doses of the three-dose
      vaccine series. Patients also undergo collection of blood samples and self-collection of
      cervical/vaginal samples (female participants only) on study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Human papillomavirus (HPV) vaccine-type-specific seroconversion rates among kidney transplant recipients who receive >= 1 doses of the vaccine >= 30 days prior to transplantation
time frame: At 12 months post-transplant
description: An estimate of the seroconversion rate will be provided along with exact Clopper-Pearson 95% confidence intervals (CIs).
measure: HPV vaccine-type-specific seroconversion rates
time frame: At 6 and 12 months post-transplant
description: Descriptive statistics, such as probabilities and exact 95% CIs, will be used to summarize HPV vaccine-type-specific seroconversion rates at 6- and 12-months post-transplantation stratified by number of doses (1, 2, or 3) of the vaccine given pre-transplant. Seroconversion probabilities will be compared between dose groups using Fisher's exact test. Armitage trend test will be used to examine whether there is a trend for increased seropositivity across dose groups.
measure: Probability of seroconversion
time frame: At 12 months post-transplant
description: Descriptive statistics, such as probabilities and exact 95% CIs, will be used to summarize probability of seroconversion at 12 months post-transplant for the following groups: a) time elapsed between last vaccine dose and the transplant procedure, e.g. < 3 months versus (vs.) > 3 months. Different groupings will be considered based on observed (e.g. median) and clinical considerations. Time will be summarized using descriptive statistics, e.g. median, interquartile range, or range; groups defined by dosing and types of post-transplant immunosuppressant medications, as well as; b) type of transplant surgery (living donor/deceased donor); c) differences in human leukocyte antigen histocompatibility between donor and recipient; d) differences by biological sex (i.e., male vs. female) of the transplant recipient.
measure: Stability of HPV vaccine-type-specific geometric mean titers (GMT)
time frame: At 6 and 12 months post-transplant
description: Stability will be evaluated in relation to changes in the type-specific GMTs between the two post-transplant time points (6- and 12-months post-transplant) and reported as follows: (i) decrease: more than 2-fold decrease, (ii) stable: within 2-fold change, and (iii) increase: greater than 2-fold increase. Stability will also be described in relation to the number of vaccine doses (1, 2 or 3) received in the pre-transplant period.
measure: Rise in HPV vaccine-type-specific GMT
time frame: At 13 months post-transplant
description: The magnitude of increase in type-specific GMTs at the 13-month post-transplant visit (i.e., 1 month after the booster dose) will be described in relation to the type-specific GMTs at the other post-transplant visits (6 and 12-months post -transplant). Patterns over time will also be explored using graphical techniques. Post-booster dose increase in type-specific GMTs will also be described in relation to the number of vaccine doses (1, 2 or 3) received in the pre-transplant period.
measure: Vaccine safety profile and allograft rejection/opportunistic infections
time frame: Up to 13 months post-transplant
description: Will be summarized using descriptive statistics, stratified by number of vaccine doses and time between the last vaccine dose and the transplant procedure.
measure: HPV detection in samples from the cervix/vagina, and oral cavity
time frame: Self-collected at baseline (pre-vaccination) and at 6- and 12- months post-vaccination
description: HPV detection in samples from the cervix/vagina, and oral cavity at baseline (pre-vaccination) and at 6- and 12-months post-vaccination, overall and by number of vaccine doses (1, 2, or 3), sexual behavior, type-specific seroconversion rates, and time elapsed between the last vaccine dose and the transplant procedure will be evaluated. All rates of HPV detection will be specified, overall and stratified by number of doses (1, 2, or 3) and time to transplant.
arm group label: Prevention (Gardasil 9 HPV vaccine)
arm group type: Experimental
description: Participants receive the first dose of the recombinant human papillomavirus nonavalent vaccine IM at baseline, at least 30 days prior to the kidney transplant surgery. The second dose is given at least one month after the first dose. The third dose is given at least five months after the first dose and at least three months after the second dose. The timing of the second and third doses is dependent on the scheduling of the kidney transplant surgery. Patients are followed up at 6- and 12-months after the kidney transplant surgery to measure vaccine-induced immune responses. Patients may receive either one, two, or all three vaccine doses prior to the kidney transplant surgery, and are offered additional visits at least one year after the surgery to complete any remaining doses of the three-dose vaccine series. Patients also undergo collection of blood samples and self-collection of cervical/vaginal samples (female participants only) on study.
intervention type: Procedure
intervention name: Biospecimen Collection
description: Undergo collection of blood samples
arm group label: Prevention (Gardasil 9 HPV vaccine)
other name: Biological Sample Collection
other name: Biospecimen Collected
other name: Specimen Collection
intervention type: Procedure
intervention name: HPV Self-Collection
description: Undergo self-collection of vaginal/cervical samples
arm group label: Prevention (Gardasil 9 HPV vaccine)
other name: At-home HPV Self Collection
other name: HPV Self Collection
other name: Human Papillomavirus Self-Collection
intervention type: Other
intervention name: Questionnaire Administration
description: Ancillary studies
arm group label: Prevention (Gardasil 9 HPV vaccine)
intervention type: Biological
intervention name: Recombinant Human Papillomavirus Nonavalent Vaccine
description: Given IM
arm group label: Prevention (Gardasil 9 HPV vaccine)
other name: Gardasil 9
other name: Nonavalent HPV VLP Vaccine
other name: Recombinant HPV Nonavalent Vaccine
other name: Recombinant Human Papillomavirus 9-valent Vaccine
criteria: 
gender: All
minimum age: 18 Years
maximum age: 49 Years
healthy volunteers: No
last name: Marc T Goodman
role: Principal Investigator
affiliation: Northwestern University
facility: 
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country: United States
responsible party type: Sponsor
mesh term: Papillomavirus Infections
mesh term: Vaccines