A Single-centre Open-label Parallel Two-arms Pilot Randomized Clinical Trial of a Booster Recombinant Zoster Vaccine in Solid-Organ Transplant Recipients
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 75
- 试验地点
- 1
- 主要终点
- Proportion of participants with ≥2-fold increase in anti-gE antibody titers from baseline
研究概览
简要总结
Shingles is caused by the same virus that causes chickenpox. After someone has chickenpox, the virus stays in the body and can become active again later in life. This is called shingles.
People who have received a solid organ transplant (such as a kidney, liver, or heart transplant) are 3 to 10 times more likely to get shingles than the general population. In transplant patients, shingles is often more severe. It can spread to other parts of the body and may cause long-lasting nerve pain. These problems can lower quality of life, increase doctor visits and hospital care, and may even affect how well the transplanted organ works.
The shingles vaccine called Shingrix® (recombinant zoster vaccine, RZV) works well in healthy adults and is generally safe for transplant patients. However, about 30% of transplant recipients still develop shingles even after receiving the recommended two doses. This may be because their immune system is weakened by the long-term medicines they take to prevent organ rejection.
The purpose of this clinical trial is to find out whether giving an extra (booster) dose of the shingles vaccine after transplant can improve the immune response in solid organ transplant recipients.
This study aims to answer the following questions:
- How many participants have at least twice as many shingles antibodies (anti-gE antibodies) four weeks after receiving the booster compared to before the booster?
- How strong and how long does the immune response last at 6 and 12 months?
- Is the booster dose safe for transplant patients? In this study, researchers will compare two groups: One group will receive a booster dose of the shingles vaccine. The other group will not receive the booster. They will compare the groups to see differences in immune response, cases of shingles despite vaccination, and any side effects.
Participants in the study will:
- Be randomly assigned (by chance) in a 2:1 ratio to either receive the booster or not.
- Have blood samples taken at the first visit, and again at 1 month, 6 months, and 12 months to measure antibody levels and immune responses.
- Be monitored for any possible side effects.
- Have their medical records reviewed for health events such as side effects or organ rejection.
详细描述
Herpes zoster (named zoster thereafter) results from reactivation of latent varicella-zoster virus (VZV) and represents a major cause of morbidity in immunocompromised populations. Among SOT recipients, the incidence of zoster is estimated to be 3-10 times higher than in the general population. In these patients, zoster is often more severe and associated with disseminated disease, and a higher risk of post-herpetic neuralgia. These complications may not only impair quality of life but also increase healthcare utilization and risk of graft dysfunction.
The recombinant zoster vaccine (RZV, Shingrix®) has shown high efficacy in immunocompetent adults. In immunocompromised populations, RZV demonstrated safety and moderate immunogenicity, including in patients who received autologous stem cell transplantation and renal transplantation. However, breakthrough infections remain frequent, affecting approximately 30% of immunocompromised patients despite prior vaccination.
The immunological mechanisms underlying these breakthrough cases likely include waning immunity and the effects of chronic immunosuppressive therapy. Since transplant recipients must receive long-term immunosuppressive drugs to prevent graft rejection, their immune system is less capable of maintaining effective vaccine-induced immunity. We hypothesize that administering an additional booster dose of RZV after transplantation could restore or enhance immune responses, leading to improved protection against zoster.
To date, no systematic clinical trial has evaluated this booster approach in solid-organ transplantation. The ZEST pilot trial therefore addresses an important evidence gap, with the potential to establish a novel vaccination strategy for this high-risk population. The trial will generate key immunological data to inform the feasibility, safety, and biological plausibility of post-transplant booster vaccination, laying the groundwork for a future multicentre randomized trial with clinical endpoints such as incidence of zoster.
SOT recipients will be identified through the transplantation center and approached during routine follow-up visits, or via mailed invitations. After receiving study information and providing written or electronic consent, participants will be randomized in a 2:1 ratio to receive a booster dose of RZV or no intervention. Randomisation and vaccination will take place either during a routine outpatient visit or in a dedicated vaccination unit to minimize additional workload for clinical staff. Blood samples will be collected at four predefined time points: at the time of vaccination (baseline) and at 1, 6, and 12 months after the booster dose. An additional blood sample at the time of transplantation may be obtained via the STCS biobank if available.
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
- None
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
- •Aged ≥18 years
- •SOT recipient who has received two doses of the Shingrix® vaccine (primary vaccination).
- •At least 6 months after transplantation
- •At least 6 months after the completion of the Shingrix® primary vaccination series.
- •At least 8 weeks have elapsed since any treated episode of acute allograft rejection or At least 6 months if B-cell depleting antibodies (e.g. rituximab, alemtuzumab) was used as part of the treatment.
- •Signature of the written informed consent.
排除标准
- •Acute febrile illness or active infection at the time of enrolment, as determined by the investigator (patients can be enrolled in a later stage).
- •Known hypersensitivity to any component of RZV.
- •Willing to become pregnant
研究组 & 干预措施
Control (no booster)
Control participants will not receive an injection but will undergo blood sampling at the same time points as the experimental group - baseline (pre-randomization), and at 1, 6 and 12 months - to ensure comparability of immunological data. They will continue standard post-transplant care and routine clinical follow-up according to institutional practice.
RZV booster
The intervention group will receive a RZV booster dose. Vaccine reconstitution will follow the manufacturer's instructions immediately before injection.
Administration will be performed by a trained study nurse or investigator under medical supervision. Participants will be observed for at least 15 minutes post-injection to detect any immediate hypersensitivity or vasovagal reaction.
No deviation from the commercial formulation or packaging is expected. The IMP used in this trial is identical to the marketed product authorized in Switzerland and the EU.
干预措施: Booster dose of the recombinant zoster vaccine (RZV, Shingrix®) (Biological)
结局指标
主要结局
Proportion of participants with ≥2-fold increase in anti-gE antibody titers from baseline
时间窗: 4 weeks after booster dose
The primary outcome of this study is the humoral immune response 4 weeks after the booster dose of RZV. This will be defined as the proportion of participants achieving at least a two-fold increase in anti-gE antibody titers compared with baseline levels, measured by anti-gE ELISA.
次要结局
- Frequency of VZV-specific CD4+ T-cells, (as % of total CD4+ T-cells)(4 weeks, 6 months and 12 months after booster dose)
- Geometric mean anti-gE antibody titers(6 and 12 months after booster dose)
- Incidence of confirmed herpes zoster cases(Through study completion, an average of 1 year)
研究者
Oriol Manuel
Associated Professor
University of Lausanne Hospitals