Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT05947071 |
| Other study ID # |
RTB-019 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
August 1, 2024 |
| Est. completion date |
September 1, 2027 |
Study information
| Verified date |
January 2024 |
| Source |
National Institute of Allergy and Infectious Diseases (NIAID) |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Influenza virus is a significant pathogen in pediatric solid organ transplant (SOT)
recipients. However, these individuals respond poorly to standard-dose (SD) inactivated
influenza vaccine (IIV). Recent studies have investigated two strategies to overcome poor
immune responses in SOT recipients: (1) administration of high-dose (HD)-IIV compared to
SD-IIV and (2) two doses of SD-IIV compared to one dose of SD-IIV in the same influenza
season. One study compared HD-IIV vs. SD-IIV in adult SOT recipients and noted that HD-IIV
was safe and more immunogenic; however, the median post-transplant period was 38 months. A
phase I pediatric study comparing a single dose of HD-IIV vs. SD-IIV was safe with higher
immunogenicity, but the study was limited by small sample size and median post-transplant
vaccine administration was 26 months. In another phase II trial of adult SOT recipients, two
doses of SD-IIV one month apart compared to one-dose of SD-IIV revealed modestly increased
immunogenicity when given at a median of 18 months post-transplant. Therefore, these studies
lack both evaluation in the early post-transplant period and substantive pediatric
populations. Additionally, the administration of two-doses of HD-IIV in the same influenza
season has not been evaluated in pediatric SOT recipients. Thus, the optimal immunization
strategy for pediatric SOT recipients less than 24 months post-transplant is unknown. In
addition, immunologic predictors and correlates of influenza vaccine immunogenicity in
pediatric SOT recipients have not been well-defined.
The central hypothesis of our proposal is that pediatric SOT recipients 1-23 months
post-transplant who receive two doses of HD-quadrivalent inactivated influenza vaccine (QIV)
will have similar safety but higher Hemagglutination Inhibition (HAI) geometric mean titers
(GMTs) to influenza antigens compared to pediatric SOT recipients receiving two doses of
SD-QIV.
Description:
Study design: This is a phase II, multi-center, double-blind, randomized controlled
immunogenicity and safety trial comparing two doses of HD-QIV or two doses of SD-QIV in
pediatric SOT recipients.
Hypotheses:
1. Pediatric SOT recipients who are 1-23 months out from transplant and are administered
two doses of HD-QIV will develop higher Hemagglutination Inhibition (HAI) geometric mean
titer (GMT) to influenza antigens compared to pediatric SOT recipients receiving two
doses of SD-QIV, with Geometric Mean Titer Ratio (GMR) HD-QIV/SD-QIV greater than 1.0.
2. Administration of HD-QIV in pediatric SOT recipients will be well tolerated and the
safety profile will be similar to SD-QIV with regards to solicited local and systemic
post-administration reactions.
3. Baseline immunophenotypic markers of exhaustion, immune senescence, and immune
activation at the pre-vaccine timepoint will correlate with post-vaccine HAI titers.
Study population: The study plans to enroll a total of approximately 312 pediatric heart,
liver, and/or kidney transplant recipients between 1 and 23 months post-transplantation.
Study enrollment: The enrollment period will be over three-years. Participants will be
randomized into one of two groups. Group 1 will receive two doses of SD-QIV (0.5 mL; 15μg of
each influenza antigen) whereas Group 2 will receive two doses HD-QIV (0.7 mL; 60μg of each
influenza antigen).
Influenza surveillance: Active surveillance for influenza-like symptoms will begin when
influenza season starts in each site's community, defined in previous trials as
identification of at least two positive respiratory tests for influenza, with at least 10% of
diagnostic tests positive during two consecutive weeks in the local clinical or research
laboratory. Enrollment will continue during influenza season with nasal swabs obtained at all
main visits to document the occurrence of influenza virus both prior to and after
vaccination. During the influenza season, the study staff will attempt to do a weekly
telephone and/or electronic communication with the participants to detect and document any
influenza-like illness (ILI) and any specific coronavirus disease of 2019 (COVID-19) like
symptoms.
If participants meet ILI criteria and/or any specific coronavirus disease of 2019 (COVID-19)
like symptoms (see below), an additional nasal swab will be collected*.
ILI criteria are met by occurrence of one of the conditions below:
- Fever: ≥38°C (100.4°F)
- Two or more of any of the following: respiratory symptoms (rhinorrhea, sinus congestion,
post-nasal drip, shortness of breath, cough, wheezing, sputum production, sore throat,
sneezing, watery eyes, ear pain, hoarseness); or systemic symptoms (myalgias, chills,
chest pain, or headache); or new loss of taste or new loss of smell; or gastrointestinal
symptoms (diarrhea or vomiting).
- Per investigators' discretion at each individual site, a swab is not needed if
there is a known non-respiratory cause of symptoms.
