Safety and Immunogenicity of Shingrix in Renal Transplant Recipients
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 132
- 试验地点
- 5
- 主要终点
- Safety information acquisition - Adverse events (AEs)
研究概览
简要总结
The goal of this clinical trial is to learn how well the shingles vaccine (Shingrix) works and how safe it is in adults with kidney failure who are waiting for a kidney transplant, including those who later receive a transplant. The study also aims to find out whether giving an extra (third) dose of the vaccine after transplant improves protection.
The main questions it aims to answer are:
How strong is the body's immune response to the vaccine at different time points (about 1 month, 2 years, and 3 years after vaccination) in people waiting for a kidney transplant?
Does a third dose of the vaccine after transplant improve the immune response compared to not receiving a third dose?
How long does protection from the vaccine last before and after transplant?
How safe is the vaccine in this group, including whether it affects transplant-related immune markers?
Researchers will compare people who receive a third dose of the vaccine after transplant to those who do not receive a third dose, as well as to results from similar groups studied in the past, to see if the extra dose improves immune protection.
Participants will:
Be screened to see if they can take part in the study Attend about 3 to 6 study visits over approximately 30 to 37 months Receive two doses of the shingles vaccine if they have not already been vaccinated, or complete study assessments if they were vaccinated before joining
If they receive a kidney transplant during the study, be randomly assigned (by chance) to receive either a third dose of the vaccine or no additional dose
Complete questionnaires, have physical exams if needed, and provide blood (and urine, if applicable) samples at study visits
Take part in follow-up visits to check immune response and safety, with the option to allow samples to be stored for future research
Shingrix is approved for adults aged 50 and older and for younger adults with weakened immune systems. However, giving a third dose after a kidney transplant is not standard practice and is being studied in this trial.
详细描述
This study is designed to evaluate the immunogenicity and safety of the adjuvanted recombinant glycoprotein E (gE) herpes zoster (HZ) vaccine (Shingrix) in adults with renal failure, including those who subsequently undergo kidney transplantation. Patients with chronic renal failure and transplant recipients have impaired cellular immunity due to underlying disease and immunosuppressive therapy, placing them at increased risk for herpes zoster and related complications, including post-herpetic neuralgia and disseminated varicella-zoster virus infection. Although Shingrix is recommended for immunocompromised adults, the magnitude, durability, and optimal timing of immune responses in the setting of renal failure and transplantation remain incompletely defined.
The primary objective is to determine whether Shingrix induces acceptable cellular immune responses, as measured by gE-specific T cell activity using FluoroSpot assays, and to evaluate the safety of vaccination in this population. Vaccine response (VR) is defined as a ≥2-fold increase in gE-specific IL-2 FluoroSpot responses compared to baseline, and geometric mean fold rise (GMFR) will be used to quantify the magnitude of immune responses.
Among renal transplant candidates vaccinated at study entry, the study will assess whether ≥60% achieve a vaccine response at 30 days after the second dose and whether the GMFR is at least 60% of that observed in historical immunocompetent controls. In participants who completed the two-dose Shingrix series prior to enrollment, immune response magnitude will be compared with historical controls, adjusted for time since vaccination.
For participants who undergo kidney transplantation, the study will evaluate immune responses before and after transplantation and assess the effect of a third (booster) dose of Shingrix administered post-transplant. Transplant recipients who receive a third dose will be compared with those who do not receive a third dose, with the primary comparison focused on gE-specific cellular immune responses at 1 year after transplantation. Additional comparisons will include responses at ≥2 months post-transplant and 30 days after the third dose, as well as comparisons with non-transplanted participants and historical controls following standard two-dose vaccination.
Safety will be evaluated throughout the study, including assessment of adverse events and monitoring of transplant-related immunologic parameters such as calculated panel-reactive antibodies (cPRA). The study will also assess the overall safety profile of Shingrix administered before and/or after transplantation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Study Population:
- •Adults with chronic kidney failure who are listed for kidney transplantation at participating transplant centers.
- •Inclusion Criteria:
- •Age 18 to 70 years Able and willing to provide written informed consent Currently on the waiting list for kidney transplantation at a participating institution, with anticipated transplantation occurring between >3 and 24 months after the first dose of Shingrix
- •Eligible to receive Shingrix at study entry per CDC-recommended schedule, or Previously completed the Shingrix vaccination series within 3 to 24 months prior to study entry Female participants of non-childbearing potential (e.g., tubal ligation, hysterectomy, ovariectomy, or post-menopausal ≥12 months)
- •Female participants of childbearing potential must:
- •Use adequate contraception for at least 30 days prior to vaccination Have a negative pregnancy test on the day of each vaccination Agree to continue adequate contraception during the study and for 2 months after completing the vaccination series Be considered by the investigator likely to comply with study requirements
排除标准
- •Active immunosuppressive or immunodeficient condition (e.g., malignancy, HIV infection) or receipt of immunosuppressive therapy within 3 months prior to planned vaccination that, in the investigator's opinion, may interfere with vaccine response History of herpes zoster (shingles) within the past 3 years Receipt of varicella vaccine within 3 years prior to study entry Known allergy to any component of the Shingrix vaccine Receipt of investigational drugs within 30 days prior to enrollment or planned use during the study Receipt of non-live vaccines within 2 weeks prior to any Shingrix dose or planned within 30 days after vaccination Receipt of live vaccines within 4 weeks prior to any Shingrix dose or planned within 30 days after vaccination Pregnant or breastfeeding Planned or prior multi-organ transplantation Residence or travel distance greater than 2 hours from the study site, which would interfere with study visits or timely processing of blood samples
研究组 & 干预措施
No Intervention Comparator Arm: No Third Dose (Post-Transplant)
Participants who undergo kidney transplantation within 24 months after initial vaccination will be randomized to receive no additional (third) dose of Shingrix after transplantation. These participants will undergo the same follow-up assessments to evaluate immunogenicity and safety outcomes and will serve as the comparator group.
Transplanted subject
Experimental Arm: Third Dose of Shingrix (Post-Transplant) Participants who undergo kidney transplantation within 24 months after initial vaccination will be randomized to receive a third (booster) dose of the recombinant zoster vaccine (Shingrix) after transplantation. These participants will be followed to assess immunogenicity (e.g., vaccine response and geometric mean fold rise) and safety outcomes over time.
干预措施: Shingrix (Biological)
结局指标
主要结局
Safety information acquisition - Adverse events (AEs)
时间窗: Adverse event data collected for 30 days after each vaccine dose.
Safety and tolerability data about local and systemic adverse events will be collected via vaccine diaries.
Safety information acquisition - Serious Adverse Events (SAEs) and potential immune-mediated diseases (pIMDs)
时间窗: SAEs and pIMD data collected from enrollment up to 12 months after Visit 4
Subjects will be queried about SAEs and pIMDs at every contact.
Immunology - Glycoprotein E(gE)-specific antibody and cell mediated immunity (CMI) will be measured.
时间窗: 12 months after vaccination
The kinetics and magnitude of antibody and CMI responses will be compared to immunologic data previously determined during studies of immune competent subjects.
Ascertaining occurrence of HZ in vaccinees
时间窗: At every contact from enrollment up to Month 36
Subjects will be asked to notify study team and to complete an HZ questionnaire should they develop herpes zoster during the study.
gE-Specific IL-2 T Cell Response at 12 Months After Randomization
时间窗: 12 months after vaccination
1\. gE-Specific IL-2 T Cell Response at 12 Months After Randomization Description: Cellular immune response measured by gE-specific IL-2-producing spot-forming cells (SFC) per 10⁶ peripheral blood mononuclear cells (PBMC) using FluoroSpot assay in renal transplant recipients. Comparison between participants who receive a third dose of Shingrix post-transplant and those who do not receive a third dose. Time frame: 12 months after vaccination (post-transplant)
次要结局
- Immunologic vaccine responses in patients with chronic renal failure(1 month after 2nd dose of Shingrix.)
- Vaccine Response (VR) at 30 Days After Second Dose(Time Frame: 30 days after second dose (approximately Month 3))
- Geometric Mean Fold Rise (GMFR) in gE-Specific IL-2 Responses at 30 Days After Second Dose(Time Frame: 30 days after second dose)
- GMFR in Previously Vaccinated Participants(Time Frame: Study entry, 24 months, and 36 months after vaccination)
- Immunogenicity at ≥2 Months Post-Transplant(Time Frame: ≥2 months post-transplant)
- Immune Response 30 Days After Third Dose (Post-Transplant)(30 days after third dose)
- GMFR at 1 Year Post-Randomization(12 months after randomization)