Comparison of High vs Standard Dose Influenza Vaccines in Pediatric Solid Organ Transplant Recipients
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 312
- 试验地点
- 16
- 主要终点
- Immunogenicity: Hemagglutination Inhibition (HAI) titers
研究概览
简要总结
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.
详细描述
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:
- 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.
- 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.
- 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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
All study staff, and subjects will be blinded to which vaccine the subject will receive, except for an un-blinded vaccinator. This individual will not inform the study team or the subjects which vaccine they administered to the subject. The un-blinded vaccinator will not participate in any other study activities. The pharmacy will be un-blinded and will have a record of which vaccine was given to each subject.
入排标准
- 年龄范围
- 3 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, 3-17 years of age at time of enrollment
- •Pediatric kidney, heart, and/or liver transplant recipient ≥1 month and <24 months post-transplant at the time of study immunization
- •Note: Inclusion of recipients of multiple organs is permitted but is limited to recipients of any combination of organs including kidney, heart and/or liver
- •Note: Participants undergoing re-transplantation are permitted
- •Anticipated to be available for duration of the study
- •Available by telephone, email, or text message
排除标准
- •Inability (i.e. not able to understand and provide consent) or unwillingness of a participant/parent/legal guardian to give written informed consent or comply with study protocol
- •History of severe hypersensitivity to influenza vaccination or anaphylaxis to eggs/egg protein
- •History of severe latex hypersensitivity
- •History of Guillain-Barre syndrome
- •History of lung or intestine transplant
- •HIV positive patients (testing within 24 months of enrollment)
- •Receipt of current season's influenza vaccine post-transplant prior to enrollment in the study
- •Currently pregnant or lactating (females of childbearing age may be enrolled based on self-report, urine pregnancy test must be performed prior to each influenza vaccine)
- •Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.
研究组 & 干预措施
Two Doses Standard Dose Quadrivalent Inactivated Influenza Vaccine
Two doses of SD-QIV (0.5 mL; 15µg of each influenza antigen) 28-42 days apart
干预措施: Standard Dose Quadrivalent Inactivated Influenza Vaccine (Biological)
Two Doses High Dose Quadrivalent Inactivated Influenza Vaccine
Two doses of HD-QIV (0.7 mL; 60µg of each influenza antigen) 28-42 days apart
干预措施: High Dose Quadrivalent Inactivated Influenza Vaccine (Biological)
结局指标
主要结局
Immunogenicity: Hemagglutination Inhibition (HAI) titers
时间窗: 4 weeks following the 2nd study vaccine
Antibody titers will be measured by hemagglutination inhibition assay.
Safety: solicited local and systemic post-administration reactions
时间窗: in the first 7 days following each study vaccine
Post-vaccination local adverse events (pain, tenderness, swelling/induration, erythema/redness, swelling/induration size, and erythema/redness size) and systemic adverse events (Fatigue/malaise, headache, nausea, body ache/myalgia (not at the injection site), general activity level, vomiting, and fever).
次要结局
- Immunogenicity: Hemagglutination Inhibition (HAI) titers(4 weeks following 1st and 2nd doses of each study vaccine)
- The number of participants achieving seroprotection and seroconversion for influenza virus.(4 weeks following the 1st and 2nd study vaccination)
- Durability of immunogenicity(180 days after vaccine 2)