ClinicalTrials.gov
ClinicalTrials.gov Menu

Immunogenicity of Nonavalent HPV Vaccine Administered Prior to Renal Transplantation in Adult Women: A Prospective, Single-Arm, Multi-Center Clinical Trial

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03036930
Recruitment Status : Recruiting
First Posted : January 31, 2017
Last Update Posted : June 25, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This trial studies whether the nonavalent human papillomavirus vaccine given to adult women 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.

Condition or disease Intervention/treatment Phase
Kidney Transplantation Other: Laboratory Biomarker Analysis Other: Questionnaire Administration Biological: Recombinant Human Papillomavirus Nonavalent Vaccine Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

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 9 HPV vaccine) >= 30 days prior to transplantation.

SECONDARY OBJECTIVES:

I. To evaluate the following in female kidney transplant recipients who receive >= 1 doses of the Gardasil 9 HPV vaccine prior to transplantation: HPV vaccine-type-specific seroconversion rates at 12-months post-transplantation stratified by: a) number of doses (1, 2, or 3) of the vaccine given pre-transplant; b) time elapsed between last vaccine dose and the transplant procedure; c) variations in dosing and types of post-transplant immunosuppressant medications; and interactions with type of transplant surgery (living donor/deceased donor), and d) differences in human leukocyte antigen (HLA) histocompatibility between donor and recipient.

II. To evaluate the following in female kidney transplant recipients who receive >= 1 doses of the Gardasil 9 HPV vaccine >= 30 days prior to transplantation: persistence and 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.

III. To evaluate the following in female kidney transplant recipients who receive >= 1 doses of the Gardasil 9 HPV vaccine >= 30 days prior to transplantation: 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.

IV. To evaluate the following in female kidney transplant recipients who receive >= 1 doses of the Gardasil 9 HPV vaccine >= 30 days prior to transplantation: 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 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. Participants are followed up at 6- and 12-months after the kidney transplant surgery to measure vaccine-induced immune responses. Participants 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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Immunogenicity of Nonavalent HPV Vaccine Administered Prior to Renal Transplantation in Adult Women: A Prospective, Single-Arm, Multi-Center Clinical Trial
Actual Study Start Date : June 23, 2017
Estimated Primary Completion Date : February 1, 2020
Estimated Study Completion Date : February 1, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Prevention (Gardasil 9 HPV vaccine)
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. Participants are followed up at 6- and 12-months after the kidney transplant surgery to measure vaccine-induced immune responses. Participants 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.
Other: Laboratory Biomarker Analysis
Correlative studies

Other: Questionnaire Administration
Ancillary studies

Biological: Recombinant Human Papillomavirus Nonavalent Vaccine
Given IM
Other Names:
  • Gardasil 9
  • Nonavalent HPV VLP Vaccine
  • Recombinant HPV Nonavalent Vaccine
  • Recombinant Human Papillomavirus 9-valent Vaccine




Primary Outcome Measures :
  1. Human papillomavirus (HPV) vaccine-type-specific seroconversion rates among female kidney transplant recipients who receive >= 1 doses of the vaccine >= 30 days prior to transplantation [ Time Frame: 12 months post-transplant ]
    Will provide an estimate of the rate and two approximate and one exact 95% confidence intervals (CIs). For approximate CI will use a) approximate normality of p-hat, and b) approximate normality of log(p-hat); and for exact CI will use the Clopper-Pearson exact confidence interval.


Secondary Outcome Measures :
  1. HPV vaccine-type-specific seroconversion rates [ Time Frame: 12 months post-transplant ]
    Will provide descriptive statistics such as means, rates, and exact or approximate 95% CI. Will compare stratified rates to each other, using an exact test for number doses. Will provide mean, median, and range for time elapsed for time elapsed between last vaccine dose and transplant procedure. Lists of dosing types by medication variety will be provided and summaries applied when possible and appropriate for variations in dosing and types of post-transplant immunosuppressant medications. Descriptive statistics and graphics will be used for visual comparison and assessment for differences in human leukocyte antigen (HLA) histocompatibility between donor and recipient.

  2. Persistence and stability of HPV vaccine-type-specific geometric mean titers (GMT) [ Time Frame: Up to 12 months post-transplant ]
    Will provide descriptive statistics such as means, rates, and exact or approximate 95% CI. Persistence will be measured as the difference in means between two times (6 and 12-months post-transplant) while stability will be assessed by measures of spread appropriate for the transformation at hand.

  3. Rise in HPV vaccine-type-specific GMT [ Time Frame: 13 months post-transplant ]
    Will provide descriptive statistics such as means, rates, and exact or approximate 95% CI.

  4. Vaccine safety profile and allograft rejection/opportunistic infections [ Time Frame: Up to 13 months post-transplant ]
    Will provide descriptive statistics such as means, rates, and exact or approximate 95% CI. Safety profile and infections will be listed stratified by number of doses (1, 2, or 3) and time to transplant (long, short) and summarized as possible.

  5. HPV detection in samples from the cervix/vagina, and oral cavity [ Time Frame: Up to 12 months post-transplant ]
    Will provide descriptive statistics such as means, rates, and exact or approximate 95% CI. All rates of HPV detection will be specified, overall and stratified by number of doses (1, 2, or 3) and time to transplant.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 49 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female candidate for renal transplant, expected to undergo transplant surgery >= 30 days and =< 12 months after enrollment

    • For potential participants on the institutional waiting list for deceased donor transplant, a study clinician confirms the candidate is likely to receive a transplant within the next 12 months, taking into account the candidate's priority on the waiting list, age, medical status, institutional policies, and scores like the Estimated Post-Transplant Survival (EPTS) Score and Calculated Panel Reactive Antibody (CPRA) percentage, etc
    • For potential participants expected to undergo a living donor transplant, one or more donor(s) have been identified and is/are in work-up (even though all work-up status may or may not be complete); a study clinician confirms the living donor transplant is likely to be scheduled within the next twelve months after taking into account donor work-up progress, age and medical status, and institutional policies

      • Note: the study was originally restricted to participants who were expecting to receive only living donor renal transplants; however, less than a third of kidney transplants in the United States occur with kidneys from living donors; a majority of transplants are in the setting of donation of kidneys from deceased donors; to permit efficiencies in accrual, the study is amended to also open enrollment to recipients of deceased donor kidneys
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
  • Women who are able to become pregnant must have a confirmed negative pregnancy test result within the past 28 days prior to enrollment and 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; women who have had a both ovaries removed or a tubal ligation will not be required to have a pregnancy test
  • Ability to understand and the willingness to sign a written informed consent document and medical release form
  • Willing and able to comply with trial protocol and follow-up

Exclusion Criteria:

  • Previous prophylactic HPV vaccination
  • Prior organ transplant
  • Anticipated desensitization treatment; this decision to exclude will be based on the site clinician's judgement; desensitization procedures vary somewhat among the five participating transplant centers, which does not permit proposing uniform criteria across all study sites for determining exclusion due to desensitization; in general, women who have received a prior transplant, have unsuitable scores on Calculated Panel Reactive Antibody (PRA) percentage (institution-specific thresholds), or an ABO incompatible donor are likely to undergo desensitization at one or more of the study centers; these factors, among others, will be used by the study clinician to determine exclusion due to anticipated desensitization in the study
  • Current use of any other investigational agents
  • History of allergic reactions to yeast or attributed to compounds of similar chemical or biologic composition to Gardasil 9 HPV vaccine
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant or intention to get pregnant, or breastfeeding; pregnant women are excluded from this study; women who are breastfeeding will be excluded
  • Carcinoma in situ (CIS) of the cervix or history of cervical cancer
  • History of active malignancy, including basal/squamous cell skin cancer
  • Prior hysterectomy
  • Concurrent illness, such as known psychiatric disorders or substance abuse (i.e., average alcohol consumption of more than 3 drinks per day), which in the opinion of the investigators would compromise either the patient or the integrity of the data
  • Patients on anticoagulation or with bleeding disorders should be evaluated by a physician for risk/benefit of bleeding disorders with intramuscular injections prior to study enrollment; patients determined to be at high risk for bleeding with intramuscular injections will be excluded

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03036930


Locations
United States, Alabama
University of Alabama at Birmingham Cancer Center Recruiting
Birmingham, Alabama, United States, 35233
Contact: Heather Logan    205-934-6774    heatherlogan@uabmc.edu   
Principal Investigator: E. T. Overton         
United States, California
Cedars Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Contact: Yunhee Choi    424-315-2543    yunhee.choi-kuaea@cshs.org   
Principal Investigator: Irene Kim         
UCSF Medical Center-Mount Zion Recruiting
San Francisco, California, United States, 94115
Contact: Ada Chao    415-476-2575    ada.chao@ucsf.edu   
Principal Investigator: Garrett R. Roll         
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Laura Bezler    312-694-0260    laura.bezler@northwestern.edu   
Principal Investigator: Michael Ison         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Brittany Price    507-261-8242    price.brittany@mayo.edu   
Principal Investigator: Raymund R. Razonable         
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Marc Goodman Northwestern University

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03036930     History of Changes
Other Study ID Numbers: NCI-2017-00116
NCI-2017-00116 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
N01-CN-2012-00035
NCI2015-06-02 ( Other Identifier: Northwestern University )
NWU2015-06-02 ( Other Identifier: DCP )
N01CN00035 ( U.S. NIH Grant/Contract )
P30CA060553 ( U.S. NIH Grant/Contract )
First Posted: January 31, 2017    Key Record Dates
Last Update Posted: June 25, 2018
Last Verified: June 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Vaccines
Immunologic Factors
Physiological Effects of Drugs