Immunogenicity of HPV Vaccine in Immunosuppressed Children

Sponsor

The University of New South Wales (Other)

Overall Status

Completed

CT.gov ID

NCT02263703

Collaborator

Sydney Children's Hospitals Network (Other), Women's and Children's Hospital, Australia (Other)

Enrollment

Location

Arm

115.1

Actual Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Genital HPV is the necessary cause for cervical cancer, as well as a major contributing cause of several other cancers and conditions. There are now effective vaccines against the main oncogenic HPV types, HPV16 and 18.

Most research and discussion has focused on targeting the vaccine to young women and older adolescents. Based on this, a national free HPV vaccination program for adolescent girls commenced in 2007, in Australia. However, at the time of commencement, there had been no research on the use of this vaccine in immunosuppressed. Therefore, information on the immunogenicity, safety and duration of efficacy of HPV vaccine when administered to immunosuppressed children is needed. This trial looked at a 3 dose schedule of quadrivalent HPV vaccine in a range of immunosuppressed children, with the endpoint being immunogenicity, followed for 5 years for duration of immunity.

Condition or Disease	Intervention/Treatment	Phase
Autoimmune Disease Juvenile Idiopathic Arthritis Inflammatory Bowel Disease Evidence of Liver Transplantation Kidney Transplant Infection Bone Marrow Transplant Infection	Biological: Quadrivalent HPV vaccine	Phase 3

Detailed Description

To determine the immunogenicity, safety and persistence of immunity following human papillomavirus (HPV) vaccination in three groups of immunosuppressed children: recipients of allogenic bone marrow transplant, recipients of renal and liver transplants, and patients with juvenile chronic arthritis, inflammatory bowel disease and other autoimmune conditions who are on longterm immunosuppressive therapy.

Significance: Immunosuppressed populations are diverse in terms of degree, type and duration of immunosuppression. The study compares several groups in order to address the heterogeneity of immunosuppression and how this affects vaccine response. BMT patients have extreme, severe immunosuppression in the short term, but recover immune function with time. In contrast, solid organ transplant recipients have ongoing, chronic immunosuppression. Although successful cessation of immunosuppressives in liver transplant patients has been reported, most patients require ongoing treatment. The inflammatory bowel disease group of patients represents a non-transplant group who require ongoing, often low level immunosuppression, often with corticosteroids. Our study will compare these three groups, followed up for five years for duration of immunity. Time of vaccines, time of serological measures of immune response are as follows.

Serum collections:

0 - Baseline (before HPV vaccine dose 1); 2 months - At the time of receipt of HPV vaccine dose 2 (to measure response to dose 1); 6 months - At the time of receipt of HPV vaccine dose 3 (to measure response to dose 2); 7 months - 1 month after HPV vaccine dose 3; 12 months - after HPV vaccine dose 1; 2 years after HPV vaccine dose 1; 3 years after HPV vaccine dose 1; 4 years after HPV vaccine dose 1; 5 years after HPV vaccine dose 1.

Study Design

Study Type:

Interventional

Actual Enrollment :

55 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Immunogenicity and Duration of Immunity in Immunosuppressed Children Vaccinated With Quadrivalent HPV Vaccine

Actual Study Start Date :

May 1, 2007

Actual Primary Completion Date :

Feb 1, 2016

Actual Study Completion Date :

Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HPV vaccine Quadrivalent HPV vaccine	Biological: Quadrivalent HPV vaccine Three 0.5 mL doses will be given at time 0, 2 months after the 1st dose and then 6 months after the initial dose. For kidney transplant recipients the first dose will be at least 6 months post-transplant.

Arm

Intervention/Treatment

Experimental: HPV vaccine

Quadrivalent HPV vaccine

Biological: Quadrivalent HPV vaccine

Three 0.5 mL doses will be given at time 0, 2 months after the 1st dose and then 6 months after the initial dose. For kidney transplant recipients the first dose will be at least 6 months post-transplant.

Outcome Measures

Primary Outcome Measures

Immunogenicity [2 years]
Indicator: Geometric mean four fold rises (with 95% confidence intervals) of the vaccine serotype specific IgG antibody in all participants. Proportion of subjects achieving a 4 fold rise in antibody titre for each serotype. Serum antibody levels will be measured using a Luminex immunoassay. Analysis: For each individual, the change in log-22FA levels for each serotype pre-post vaccination will be calculated. The average change will then be compared over time for each group and also between healthy and immunosuppressed groups using t-tests. Geometric mean titres of antibody for each serotype will be measured and compared at each follow up interval.

Secondary Outcome Measures

Duration of immunity [5 years]
Interpretation of Results: Persistance of immunity will be measured over 5 years, as well as the comparison of immunogenicity by immune status.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Immunosuppressed patients with following diseases; Bone marrow transplant recipients, liver transplant patients, renal transplant, Children with inflammatory bowel disease, juvenile Idiopathic arthritis and autoimmune conditions.