Hepatitis A Vaccine Dosing Regimens Among Pediatric Patients on Immunosuppressive Therapy

Study Overview
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Brief Summary
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The study is a prospective, single centre, double-blinded randomized controlled trial whose goal is to compare the immune response of a population of immunosuppressed pediatric rheumatology patients on immunosuppressive medications to two different doses of Hepatitis A vaccine. The objectives are (a) to confirm that adolescents, like their adult counterparts, have a reduced immune response to hepatitis A vaccine, and (b) to compare the immunogenicity of two different dosing options of vaccine for this age group after one and two doses. A total of 60 adolescents aged 12 - 15 years with confirmed chronic rheumatologic conditions for which they are being treated with an immunosuppressive therapy will be recruited from the Rheumatology Clinic at Alberta Children's Hospital (ACH). Those found to have no immunity to hepatitis A will be enrolled. Informed, written consent will be obtained from the parent or guardian of subject, with assent obtained from the study subjects. Subjects will be randomly assigned to two doses of either Avaxim Pediatric® or Avaxim ® (adult) vaccine (Sanofi Pasteur Canada), six months apart, with hepatitis A titres done at baseline and one month after each dose. Both formulations are licensed for this age group.

Detailed Description
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This is a prospective, single centre, randomized, controlled trial comparing immune responses to two doses of a licensed Hepatitis A vaccine in children. Subjects will receive 2 doses (0.5 mL each) of the assigned study vaccine (Avaxim Pediatric® or Avaxim ® (adult) vaccine). One lot of each vaccine formulation will be studied. All subjects will provide safety observations using a diary and sequential blood samples will be obtained to measure serologic/immunologic responses. The study population will include 60 subjects with confirmed rheumatologic condition on immunosuppressive medication, males and females, in the age range 12 - 15 years. The maximum age at enrollment is 15 years and 5 months, to allow for up to 7 months in which to complete 2 doses of vaccine before age 16 years.Both vaccine formulations used in this trial has been licensed for use in Canada in the age range of the subjects being studied.

Official Title
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A Randomized Controlled Trial of Two Hepatitis A Vaccine Doses Among Adolescents With Juvenile Idiopathic Arthritis and Crohn's Disease on Immunosuppressive Therapy: A Pilot Study

Conditions
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Autoimmune Rheumatologic Disease

Intervention / Treatment
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* Biological: Avaxim Pediatric®
* Biological: Avaxim ® (adult)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent provided for the subject by a parent or legal guardian. Written informed assent from the participants themselves. Subjects whose parents the investigator believes can and will comply with the requirements of the protocol (i.e. return for follow-up visits, record safety observations, able to converse with study personnel and contactable by telephone). Age 12 years to 15 years and 5 months Confirmed chronic rheumatologic condition Maintained on any immunosuppressive medication with the exception of pulse steroids Exclusion Criteria: Systemic hypersensitivity to any Hepatitis A vaccine component such as neomycin, 2-phenoxyethanol, formaldehyde, aluminum hydroxide, Medium 199 Hanks, or Polysorbate 80. Thrombocytopenia or any bleeding disorder that contraindicates IM injection or blood collection. Receipt of blood or any blood-derived products (including IVIG) within the past 3 months. Previous laboratory-confirmed infection with Hepatitis A Previous vaccination with any Hepatitis A vaccine The following conditions are temporary or self-limiting exclusions so a subject can be vaccinated once the condition has resolved and no other exclusion criteria exist: Current febrile illness or oral temperature of ≥ 38.5 °C (or equivalent by other route) or other moderate to severe illness within 24 hours before study vaccine administration Receipt of any Hepatitis B vaccine within 28 days of planned study vaccine doses. When Twinrix® has been studied, the response to Hepatitis B is amplified by the presence of Hepatitis A. It is unknown whether the reverse is also true. Routine childhood vaccines (except MMR and Varicella) must be separated from a study vaccination by at least 7 days.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Avaxim Pediatric®<br>2 doses (0.5 mL each) six months apart of Avaxim Pediatric® | Biological: Avaxim Pediatric®<br>* 2 doses (0.5 mL each) 6 months apart of Avaxim Pediatric® vaccine.<br>|
| Active Comparator: Avaxim ® (adult)<br>2 doses (0.5 mL each) six months apart of Avaxim ® (adult) | Biological: Avaxim ® (adult)<br>* 2 doses (0.5 mL each) 6 months apart of Avaxim ® (adult) vaccine.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hepatitis A antibodies titre |  | 6 to 7 months |