Chronic Kidney Disease
Conditions
Keywords
chronic kidney disease, children, dialysis, kidney transplant, human papilloma virus, Gardasil, Chronic kidney disease (non-dialysis, dialysis, and kidney transplant) secondary to any cause.
Brief summary
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.
Interventions
DRUGGardasil® 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.
Sponsors
Merck Sharp & Dohme LLC
Johns Hopkins University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
9 Years to 21 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients 9-15 Years of Age With CKD Achieving Seropositivity (IgG Assay) at Blood Draw 2 | Month 7 | 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. |
| 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 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 25 |
| 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.
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. | 9 |
| 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.
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. | 23 |
| Total | 57 |
Baseline characteristics
| Characteristic | 1. Chronic Kidney Disease, NKF Stage 1-4 | 2. ESRD (Dialysis) | 3. Kidney Transplant Recipient | Total |
|---|---|---|---|---|
| Age, Customized >=11, <=21, years | 25 Participants | 9 Participants | 23 Participants | 57 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 4 Participants | 6 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 3 Participants | 9 Participants |
| Race (NIH/OMB) White | 12 Participants | 2 Participants | 14 Participants | 28 Participants |
| Sex: Female, Male Female | 25 Participants | 9 Participants | 23 Participants | 57 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 9 | 0 / 23 |
| other Total, other adverse events | 4 / 25 | 0 / 9 | 4 / 23 |
| serious Total, serious adverse events | 0 / 25 | 0 / 9 | 0 / 23 |
Outcome results
Primary
Percentage of Patients 16-21 Years of Age on Dialysis Achieving Seropositivity (IgG Assay) at Blood Draw 2
Time frame: Month 7
Population: Some patients did not complete all 3 blood draws because of (1) previous vaccination at primary care physician's office, which precluded blood draws 1 and/or 2; (2) inconsistent clinic visits, which precluded the 2nd or 3rd blood draw; and/or (3) administrative censoring in July 2012.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HPV 6 | Percentage of Patients 16-21 Years of Age on Dialysis Achieving Seropositivity (IgG Assay) at Blood Draw 2 | 100 percentage of participants |
| HPV 11 | Percentage of Patients 16-21 Years of Age on Dialysis Achieving Seropositivity (IgG Assay) at Blood Draw 2 | 100 percentage of participants |
| HPV 16 | Percentage of Patients 16-21 Years of Age on Dialysis Achieving Seropositivity (IgG Assay) at Blood Draw 2 | 100 percentage of participants |
| HPV 18 | Percentage of Patients 16-21 Years of Age on Dialysis Achieving Seropositivity (IgG Assay) at Blood Draw 2 | 100 percentage of participants |
Primary
Percentage of Patients 16-21 Years of Age With a Kidney Transplant Achieving Seropositivity (IgG Assay) at Blood Draw 2
Time frame: Month 7
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HPV 6 | Percentage of Patients 16-21 Years of Age With a Kidney Transplant Achieving Seropositivity (IgG Assay) at Blood Draw 2 | 50 percentage of participants |
| HPV 11 | Percentage of Patients 16-21 Years of Age With a Kidney Transplant Achieving Seropositivity (IgG Assay) at Blood Draw 2 | 57 percentage of participants |
| HPV 16 | Percentage of Patients 16-21 Years of Age With a Kidney Transplant Achieving Seropositivity (IgG Assay) at Blood Draw 2 | 100 percentage of participants |
| HPV 18 | Percentage of Patients 16-21 Years of Age With a Kidney Transplant Achieving Seropositivity (IgG Assay) at Blood Draw 2 | 64 percentage of participants |
Primary
Percentage of Patients 16-21 Years of Age With CKD Achieving Seropositivity (IgG Assay) at Blood Draw 2
Time frame: Month 7
Population: Some patients did not complete all 3 blood draws because of (1) previous vaccination at primary care physician's office, which precluded blood draws 1 and/or 2; (2) inconsistent clinic visits, which precluded the 2nd or 3rd blood draw; and/or (3) administrative censoring in July 2012.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HPV 6 | Percentage of Patients 16-21 Years of Age With CKD Achieving Seropositivity (IgG Assay) at Blood Draw 2 | 100 percentage of participants |
| HPV 11 | Percentage of Patients 16-21 Years of Age With CKD Achieving Seropositivity (IgG Assay) at Blood Draw 2 | 100 percentage of participants |
| HPV 16 | Percentage of Patients 16-21 Years of Age With CKD Achieving Seropositivity (IgG Assay) at Blood Draw 2 | 100 percentage of participants |
| HPV 18 | Percentage of Patients 16-21 Years of Age With CKD Achieving Seropositivity (IgG Assay) at Blood Draw 2 | 100 percentage of participants |
Primary
Percentage of Patients 9-15 Years of Age on Dialysis Achieving Seropositivity (IgG Assay) at Blood Draw 2
Time frame: Month 7
Population: Some patients did not complete all 3 blood draws because of (1) previous vaccination at primary care physician's office, which precluded blood draws 1 and/or 2; (2) inconsistent clinic visits, which precluded the 2nd or 3rd blood draw; and/or (3) administrative censoring in July 2012.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HPV 6 | Percentage of Patients 9-15 Years of Age on Dialysis Achieving Seropositivity (IgG Assay) at Blood Draw 2 | 100 percentage of participants |
| HPV 11 | Percentage of Patients 9-15 Years of Age on Dialysis Achieving Seropositivity (IgG Assay) at Blood Draw 2 | 100 percentage of participants |
| HPV 16 | Percentage of Patients 9-15 Years of Age on Dialysis Achieving Seropositivity (IgG Assay) at Blood Draw 2 | 100 percentage of participants |
| HPV 18 | Percentage of Patients 9-15 Years of Age on Dialysis Achieving Seropositivity (IgG Assay) at Blood Draw 2 | 100 percentage of participants |
Primary
Percentage of Patients 9-15 Years of Age With a Kidney Transplant Achieving Seropositivity (IgG Assay) at Blood Draw 2
Time frame: Month 7
Population: Some patients did not complete all 3 blood draws because of (1) previous vaccination at primary care physician's office, which precluded blood draws 1 and/or 2; (2) inconsistent clinic visits, which precluded the 2nd or 3rd blood draw; and/or (3) administrative censoring in July 2012.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HPV 6 | Percentage of Patients 9-15 Years of Age With a Kidney Transplant Achieving Seropositivity (IgG Assay) at Blood Draw 2 | 88 percentage of participants |
| HPV 11 | Percentage of Patients 9-15 Years of Age With a Kidney Transplant Achieving Seropositivity (IgG Assay) at Blood Draw 2 | 75 percentage of participants |
| HPV 16 | Percentage of Patients 9-15 Years of Age With a Kidney Transplant Achieving Seropositivity (IgG Assay) at Blood Draw 2 | 100 percentage of participants |
| HPV 18 | Percentage of Patients 9-15 Years of Age With a Kidney Transplant Achieving Seropositivity (IgG Assay) at Blood Draw 2 | 88 percentage of participants |
Primary
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.
Time frame: Month 7
Population: Some patients did not complete all 3 blood draws because of (1) previous vaccination at primary care physician's office, which precluded blood draws 1 and/or 2; (2) inconsistent clinic visits, which precluded the 2nd or 3rd blood draw; and/or (3) administrative censoring in July 2012.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HPV 6 | Percentage of Patients 9-15 Years of Age With CKD Achieving Seropositivity (IgG Assay) at Blood Draw 2 | 100 percentage of participants |
| HPV 11 | Percentage of Patients 9-15 Years of Age With CKD Achieving Seropositivity (IgG Assay) at Blood Draw 2 | 100 percentage of participants |
| HPV 16 | Percentage of Patients 9-15 Years of Age With CKD Achieving Seropositivity (IgG Assay) at Blood Draw 2 | 100 percentage of participants |
| HPV 18 | Percentage of Patients 9-15 Years of Age With CKD Achieving Seropositivity (IgG Assay) at Blood Draw 2 | 100 percentage of participants |