Immunogenicity and Safety of Consecutive High-Dose vs. Standard-Dose Influenza Vaccines Administered Over Successive Seasons in Lung Transplant Recipients
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Immunogenicity: Geometric Mean Titers of Influenza Vaccine Antibodies
研究概览
简要总结
This will be a follow-up study to the "Comparison of High Dose vs. Standard Dose Influenza Vaccine in Lung Allograft Recipient" study (DMID Protocol Number 22-0014) at Vanderbilt University Medical Center.
Lung transplantation is a life-saving therapy for patients with advanced lung disease, and is also associated with an improvement in quality of life. However, due to the need for life-long immunosuppression to prevent acute cellular rejection and chronic lung allograft dysfunction ("chronic rejection"), lung transplant recipients are at risk for developing major infections. In fact, one-year survival is 85%, with infection being the leading cause of death within the first year post-transplant. We will conduct a follow-up phase II, randomized, double-blind trial to assess the impact of subsequent administration of two doses of HD-IIV compared to two doses of SD-IIV among lung recipients during the early post-transplant period. Demonstration of improved immunogenicity from two doses of HD-IIV over consecutive influenza seasons would provide potential broad benefit in reducing influenza disease and its associated complications in lung transplant recipients. Moreover, studying vaccine immunogenicity and safety in the same participants over consecutive years can provide insight into the influence of immunosuppression levels and allograft aging on vaccine-mediated immune modulation. This proposed study design will contribute significantly to influenza vaccination guidance and policy for the highly vulnerable lung transplant population. This proposed study is designed to address several key knowledge gaps in vaccine-mediated protection of lung transplant recipients against influenza:
- Is there increased immunogenicity with administration of one or two doses of HD-IIV or SD-IIV in the subsequent season compared to two doses of HD-IIV or SD-IIV in the first season?
- What is the durability of the humoral and cellular immune response between influenza seasons and does two doses of HD-IIV or SD-IIV sustain higher HAI titers compared to two doses of HD-IIV or SD-IIV in the first season?
- What is the impact of maintenance immunosuppression levels on influenza vaccine immunogenicity within the same participant?
- Will the optimal immunogenic vaccination strategy be associated with an acceptable long-term safety profile over successive influenza seasons, including injection-site and systemic reactions, allosensitization, and organ rejection?
详细描述
The study is a phase II, single-center, double-blind, randomized controlled immunogenicity and safety trial comparing two doses of HD-IIV to two doses of SD-IIV over two consecutive years in lung transplant recipients. At study enrollment, following consent, participants will receive either HD-IIV or SD-IIV , with study arm assignments based on DMID protocol number 22-0014. Therefore, participants will ultimately receive four total doses of either HD-IIV or four total doses of SD-IIV over two consecutive influenza seasons.
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. If the study vaccine is provided in a blinded manner, then research staff will be able to administer the vaccine, and an un-blinded vaccinator will not be necessary. 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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Lung transplant recipient who enrolled and completed Visits 1, 2, and 3 of the DMID protocol number 22-0014 during the prior 2024-2025 or 2025-2026 influenza season, respectively
- •Anticipated to be available for the duration of the study
- •Can be reached by telephone, text message, email, or electronic health record messaging
排除标准
- •Recipient of multi-organ, extra-pulmonary, and/or hematopoietic stem cell transplant
- •Recipient of a re-do lung transplant
- •History of Guillain-Barre syndrome
- •History of receiving the current season's influenza vaccine prior to study enrollment and/or Visit 1 of this follow-up study
- •Pregnant person
- •Laboratory-confirmed influenza disease after September 1st in the current influenza season and before enrollment in this follow-up study (patient can still receive the second influenza vaccination despite proven influenza disease after enrollment)
- •CMVIG/IVIG/SCIG receipt within 28 days of each vaccine
- •Receipt of rituximab or other B-cell depleting antibody (including proteasome inhibitors) therapy within 3 months of 1st vaccine dose (Day 0)
- •Receipt of T-cell depleting therapies (anti-thymocyte globulin, alemtuzumab, daratumumab) between the completion of Visit 3 of the initial study and enrollment in this follow-up study
- •Investigator concern about study participation
- •Note: Criteria for temporarily delaying vaccine administration: The following conditions are temporary or self-limiting, and a participant may be included in the study once the condition has resolved, provided that the participant is otherwise eligible:
- •Fever ≥100.4ºF/38.0ºC (oral measurement), or an acute severe illness within 48 hours of enrollment
- •Receipt of any live vaccines within four weeks or any inactivated vaccines within two weeks prior to potential study vaccination
- •No children have been enrolled in the DMID protocol number 22-0014; therefore, only adults will be enrolled in this current study
研究组 & 干预措施
Fluzone: Two Doses High Dose Inactivated Influenza Vaccine
Fluzone: Two Doses of HD-IIV
干预措施: Fluzone High Dose Inactivated Influenza Vaccine (Biological)
Fluzone: Two Doses Standard Dose Inactivated Influenza Vaccine
Fluzone: Two Doses of of SD-IIV
干预措施: Fluzone Standard Dose Inactivated Influenza Vaccine (Biological)
结局指标
主要结局
Immunogenicity: Geometric Mean Titers of Influenza Vaccine Antibodies
时间窗: Four-eight weeks following the second study vaccination
HAI GMT to influenza antigens four-eight weeks following the second study vaccination
Safety - The number of participants reporting solicited injection site reactions
时间窗: Within 7 days post vaccination
Solicited Injection-site Adverse Events Following each Vaccination Dose (Pain, Tenderness, Swelling/induration, Erythema/redness)
Safety - The number of participants reporting systemic adverse events
时间窗: Within 7 days post vaccination
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
- Geometric Mean Titers of Influenza Vaccine Antibodies after One or Two Doses in the Second Year(Within four to eight weeks post vaccination after 1st and 2nd vaccine)
- The number of participants achieving seroprotection and seroconversion for influenza virus after receiving either two doses of HD-IIV or two doses of SD-IIV over two consecutive years(Four to eight weeks after vaccination)
研究者
Natasha Halasa
Professor of Pediatric Infectious Diseases
Vanderbilt University Medical Center