Antibody Response to Human Papillomavirus Recombinant Vaccine (Gardasil®) in Girls and Young Women With Chronic Kidney Disease

People with chronic kidney disease are known to have immune response abnormalities, including a diminished response to some vaccinations. Those with chronic kidney disease have a disproportionate burden of HPV 6-, 11-, 16- and/or 18-related genital tract disease. Due to immune response abnormalities, the CKD population may or may not respond to the recommended three-dose regimen of Gardasil®, a vaccine intended to protect against HPV 6-, 11-, 16-, and 18-related genital tract disease. The objective of this study is to measure the antibody response to Gardasil® in female patients 9-21 years of age with chronic kidney disease (CKD) (Stage 1-4), end-stage kidney disease (Stage 5 CKD), and status-post kidney transplant. Gardasil® vaccine will be administered according to the FDA-approved schedule. Blood samples to measure antibody levels to vaccine strains of human papillomavirus (HPV) will be obtained at months 0, 7 and 24.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Drug: Gardasil® Vaccine (FDA-approved vaccination regimen)

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Healthcare & Children's Healthcare of Atlanta Pediatric Nephrology Clinic
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University Harriet Lane Kidney Center, Rubenstein Child Health Bldg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

Females, aged 9-21 years, in the following groups:

• CKD (defined as estimated glomerular filtration rate between 90 ml/min/1.73m2 and 15 ml/min/1.73m2, as calculated by the Schwartz formula)
• ESRD (eGFR < 15 ml/min/1.73m2, or receiving chronic dialysis [peritoneal or hemodialysis])
• Status-post kidney transplant

Exclusion Criteria:

• Within first 3 months post kidney transplant
• Within 3 months of kidney rejection episode
• Hypersensitivity to active substances or excipients of Gardasil vaccine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 1. Chronic Kidney Disease, NKF Stage 1-4; Gardasil vaccine series will be administered according to FDA-approved schedule, as recommended by the Centers for Disease Control and Prevention and the American Academy of Pediatrics. Geometric antibody titers among those with chronic kidney disease will be compared to titers in the general population measured during Phase III clinical studies by Merck & Co, Inc, to prove efficacy of the vaccine and obtain FDA approval.	Drug: Gardasil® Vaccine (FDA-approved vaccination regimen); Standard Gardasil® 3-dose regimen (0.5 mL/dose; doses at 0, 2 and 6 months) delivered to females with chronic kidney disease 9-21 years of age.
Other: 2. ESRD (dialysis); Gardasil vaccine series will be administered according to FDA-approved schedule, as recommended by the Centers for Disease Control and Prevention and the American Academy of Pediatrics. Geometric antibody titers among those with ESRD will be compared to titers in the general population measured during Phase III clinical studies by Merck & Co, Inc, to prove efficacy of the vaccine and obtain FDA approval.	Drug: Gardasil® Vaccine (FDA-approved vaccination regimen); Standard Gardasil® 3-dose regimen (0.5 mL/dose; doses at 0, 2 and 6 months) delivered to females with chronic kidney disease 9-21 years of age.
Other: 3. Kidney Transplant Recipient; Gardasil vaccine series will be administered according to FDA-approved schedule, as recommended by the Centers for Disease Control and Prevention and the American Academy of Pediatrics. Geometric antibody titers among those with a kidney transplant will be compared to titers in the general population measured during Phase III clinical studies by Merck & Co, Inc, to prove efficacy of the vaccine and obtain FDA approval.	Drug: Gardasil® Vaccine (FDA-approved vaccination regimen); Standard Gardasil® 3-dose regimen (0.5 mL/dose; doses at 0, 2 and 6 months) delivered to females with chronic kidney disease 9-21 years of age.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients 9-15 Years of Age With CKD Achieving Seropositivity (IgG Assay) at Blood Draw 2	The primary outcome was antibody response to each of four HPV genotypes contained within the HPV vaccine at the time periods specified for the blood draws. Antibody levels, measured by Merck GmbH, were initially determined using the competitive Luminex immunoassay(cLIA; Merck GmbH), the assay used in the original licensing studies. Seropositivity was defined as being above thresholds set at 20, 16, 20, and 24 milliMerck units for HPV genotypes 6, 11, 16, and 18, respectively, as determined in phase 2 studies among patients who were immunocompetent. Antibody levels were reanalyzed using the newer, more sensitive IgG cLIA in stored serum from blood draws 2 and 3. Seropositivity for this assay was defined as being above thresholds set at 15, 15, 7, and 10 milliMerck units for HPV genotypes 6, 11, 16, and 18, respectively.	Month 7
Percentage of Patients 16-21 Years of Age With CKD Achieving Seropositivity (IgG Assay) at Blood Draw 2		Month 7
Percentage of Patients 9-15 Years of Age on Dialysis Achieving Seropositivity (IgG Assay) at Blood Draw 2		Month 7
Percentage of Patients 16-21 Years of Age on Dialysis Achieving Seropositivity (IgG Assay) at Blood Draw 2		Month 7
Percentage of Patients 9-15 Years of Age With a Kidney Transplant Achieving Seropositivity (IgG Assay) at Blood Draw 2		Month 7
Percentage of Patients 16-21 Years of Age With a Kidney Transplant Achieving Seropositivity (IgG Assay) at Blood Draw 2		Month 7

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Jeffrey J Fadrowski, MD, MHS, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: December 9, 2008
• First Submitted That Met QC Criteria: December 9, 2008
• First Posted (Estimate): December 11, 2008

Study Record Updates

• Last Update Posted (Actual): July 24, 2017
• Last Update Submitted That Met QC Criteria: July 20, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: children; chronic kidney disease; dialysis; kidney transplant; Gardasil; human papilloma virus; Chronic kidney disease (non-dialysis, dialysis, and kidney transplant) secondary to any cause.
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: NA_00020699