Autoimmune Rheumatologic Disease
Conditions
Brief summary
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
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.
Interventions
BIOLOGICALAvaxim Pediatric®
2 doses (0.5 mL each) 6 months apart of Avaxim Pediatric® vaccine.
BIOLOGICALAvaxim ® (adult)
2 doses (0.5 mL each) 6 months apart of Avaxim ® (adult) vaccine.
Sponsors
University of Calgary
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 15 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Hepatitis A Antibodies Titre | 6 to 7 months |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Avaxim Pediatric® 2 doses (0.5 mL each) six months apart of Avaxim Pediatric®
Avaxim Pediatric®: 2 doses (0.5 mL each) 6 months apart of Avaxim Pediatric® vaccine. | 10 |
| Avaxim ® (Adult) 2 doses (0.5 mL each) six months apart of Avaxim ® (adult)
Avaxim ® (adult): 2 doses (0.5 mL each) 6 months apart of Avaxim ® (adult) vaccine. | 9 |
| Total | 19 |
Baseline characteristics
| Characteristic | Avaxim ® (Adult) | Total | Avaxim Pediatric® |
|---|---|---|---|
| Age, Categorical <=18 years | 9 Participants | 19 Participants | 10 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Conventional and Biologic Disease Modifying Anti-Rheumatic Drugs | 9 Participants | 19 Participants | 10 Participants |
| Diagnosis Crohn | 2 participants | 3 participants | 1 participants |
| Diagnosis JIA | 7 participants | 16 participants | 9 participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Canada | 9 participants | 19 participants | 10 participants |
| Sex: Female, Male Female | 4 Participants | 11 Participants | 7 Participants |
| Sex: Female, Male Male | 5 Participants | 8 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 9 |
| other Total, other adverse events | 2 / 10 | 1 / 9 |
| serious Total, serious adverse events | 0 / 10 | 0 / 9 |
Outcome results
Primary
Hepatitis A Antibodies Titre
Time frame: 6 to 7 months
Population: Received both vaccinations and serum sample at 4 time-points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Avaxim Pediatric® | Hepatitis A Antibodies Titre | 1 month after (t3) | 343.0 IU/L |
| Avaxim Pediatric® | Hepatitis A Antibodies Titre | Baseline (t1) | 9.4 IU/L |
| Avaxim Pediatric® | Hepatitis A Antibodies Titre | Second dose (t4) | 3975.0 IU/L |
| Avaxim Pediatric® | Hepatitis A Antibodies Titre | First dose (t2) | 394.7 IU/L |
| Avaxim ® (Adult) | Hepatitis A Antibodies Titre | Second dose (t4) | 9372.0 IU/L |
| Avaxim ® (Adult) | Hepatitis A Antibodies Titre | Baseline (t1) | 9.0 IU/L |
| Avaxim ® (Adult) | Hepatitis A Antibodies Titre | 1 month after (t3) | 310.2 IU/L |
| Avaxim ® (Adult) | Hepatitis A Antibodies Titre | First dose (t2) | 810.6 IU/L |