Preventive Human Papillomavirus (HPV) Vaccine Trial in Kidney Transplant Recipients

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

51 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-06-23

Study Completion Date

2026-03-06

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Human Papillomavirus Infection Human Papillomavirus-Related Carcinoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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. 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.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo collection of blood samples

HPV Self-Collection

Intervention Type PROCEDURE

Undergo self-collection of vaginal/cervical samples

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Recombinant Human Papillomavirus Nonavalent Vaccine

Intervention Type BIOLOGICAL

Given IM

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Biospecimen Collection

Undergo collection of blood samples

Intervention Type PROCEDURE

HPV Self-Collection

Undergo self-collection of vaginal/cervical samples

Intervention Type PROCEDURE

Questionnaire Administration

Ancillary studies

Intervention Type OTHER

Recombinant Human Papillomavirus Nonavalent Vaccine

Given IM

Intervention Type BIOLOGICAL

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Biological Sample Collection Biospecimen Collected Specimen Collection At-home HPV Self Collection HPV Self Collection Human Papillomavirus Self-Collection Gardasil 9 Nonavalent HPV VLP Vaccine Recombinant HPV Nonavalent Vaccine Recombinant Human Papillomavirus 9-valent Vaccine

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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
* Notes:

* Living and deceased donor transplant recipients: 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 (from version 3.5) to also open enrollment to recipients of deceased donor kidneys
* Transplant recipients of both genders: The study was originally designed to be conducted only among women; however, in October 2018, the Food and Drug Administration (FDA) approved an age expansion indication for the Gardasil 9 HPV vaccine for both women and men up to 45 years (from the originally approved upper age limit of 26 years), thus opening a new clinical cancer preventative option for middle-age adults of both genders; the primary endpoint for the study is HPV-vaccine-type-specific seroconversion rates, which are not expected to be differential by gender, based on extrapolating from the uniformly high (\> 99%) seroconversion rates observed regardless of gender in studies among immunocompetent individuals; however, HPV vaccine-type-specific titer levels (GMT) differences by gender will be analyzed as a secondary endpoint, given variability in immune response titer levels observed between males and females in immunocompetent individuals (related to the differences in body mass index or hitherto unproven factors related to hormone-immune interactions); another advantage of expanding this study to males will be to facilitate efficiencies in accrual, since men constitute the majority (55%-65%) of all kidney transplant recipients in the United States; although a majority of current HPV-associated cancers among solid organ transplant recipients occur among women, there is increasing evidence of the link between HPV infection and oropharyngeal cancers that disproportionately affect men; HPV-related oropharyngeal cancers are now the most common HPV-related cancers in the United States, surpassing even the incidence of cervical cancer; the expansion of enrollment to men will also allow this study to look at the effect of HPV vaccination on persistence of oral HPV infection as a secondary/exploratory endpoint in the context of transplant-related immunosuppression
* Age 18-49 years. We have chosen to focus on adults aged 18-49 for this initial study in transplant recipients for a few reasons. Prior data for HPV vaccine response exists for adults up to 49 years of age, providing an important external comparison group for our study. Immune response and exposure wane as age increases and we want to minimize the potential for age-related confounding of our study outcome. For this initial trial, we thought it best to maintain homogeneity in the study population to the extent possible. Finally, given that about half of renal transplant recipients in the United States (U.S.) are between the ages of 18-49 years, selecting this age range permits efficiency in study accrual
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
* The effects of the Gardasil 9 HPV vaccine on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because there have been no adequate and well-controlled studies of Gardasil 9 in pregnant women, 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; women who have had a both ovaries removed or a tubal ligation will not be required to have a pregnancy test; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
* 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 a participant who may need desensitization 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 is warranted for a particular participant 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
* For female participants: Pregnant or intention to get pregnant, or breastfeeding; pregnant women are excluded from this study because the safety and effectiveness of Gardasil 9 HPV vaccine have not been established in pregnant women; it is not known whether Gardasil 9 is excreted in human milk; because many drugs are excreted in human milk, caution should be exercised when Gardasil 9 is administered to a nursing woman; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Gardasil 9, women who are breastfeeding will be excluded
* History of cervical cancer or anal cancer
* History of active malignancy, including basal/squamous cell skin cancer
* 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

Minimum Eligible Age

18 Years

Maximum Eligible Age

49 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Marc T Goodman

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

Site Status

Cedars Sinai Medical Center

Los Angeles, California, United States

Site Status

UCSF Medical Center-Mount Zion

San Francisco, California, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document