Comprehensive Characterization of Immune Response Induced by Adjuvanted Glycoprotein E (gE)-Based Recombinant VAccine Zoster in Vulnerable Population Receiving ImmunOmodulaNt Therapies
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Primary endpoint:
研究概览
简要总结
Varicella-zoster virus (VZV) is one of the eight herpesviruses that infect humans by manifesting as varicella. After primary infection VZV remains latent for life. In 30% of individuals the virus reactivates causing a secondary infection, herpes zoster (HZ). The most common complication of HZ is post-herpetic neuralgia (PHN) and, in severe cases, disseminated infection and death. The incidence of HZ increases as cell-mediated immunity (CMI) declines due to advanced age or the administration of immunomodulatory or immunosuppressive therapies. With the approval of the recombinant adjuvanted glycoprotein E (gE) vaccine (RZV; Shingrix™, GSK) also in immunocompromised individuals (IC) HZ is now considered a vaccine preventable disease. The development of novel biologic therapies has revolutionized the treatment of inflammatory skin conditions improving clinical responses in psoriasis and psoriatic arthritis patients. Although the overall safety records of biologic therapies are outstanding, there is evidence of an increased risk of contracting viral infections by nature of their inherent immunomodulatory and immunosuppressive effects.
Primary myelofibrosis (MF) is a myeloproliferative neoplasm. The development and approval of ruxolitinib, the first JAK1/2 inhibitor indicated to treat MF, has improved patient outcomes and overall survival. However, JAK inhibitors also suppressed the immune system impairing Natural Killer cell function and virus-specific T cell response. These may potentially result in increased infections (and in particular of VZV reactivation).
Given the increased risk of HZ associated with immunomodulant therapy, data on the immunogenicity and safety of RZV in IC populations are urgently needed.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •• Patients over 18 years of age;
- •All genders are eligible for the study;
- •Patients with psoriasis receiving immunomodulant therapy (anti-TNF);
- •Patients with psoriasis who do not require immunomodulant therapy;
- •Patients with myelofibrosis receiving immunomodulant therapy (anti-JAK, such as Ruxolitinib);
- •Patients with myelofibrosis not receiving immunomodulant treatment;
- •Life expectancy (as estimated by the treating physician) ≥ 12 months or more;
- •Signed informed consent.
排除标准
- •• At the end of the observation period;
- •In case of death;
- •If informed consent is revoked.
研究组 & 干预措施
Patients with psoriasis treated with biologics vaccined with Shigrix
Diagnostic Test: Immunological assays for characterization of T-cell mediated response ELISpot assay will be performed for monitoring of T-cell mediated response against the Varicella-Zoster antigens.
Diagnostic Test: Measurement of VZV- and gE-specific levels for monitoring humoral response
Diagnostic Test: Frequency of natural killer cells positive for the expression of 107a after co-culture with serum and infected cells for monitoring ADCC potential
Patients with Psoriasis untreated with biologics vaccined with Shigrix
Diagnostic Test: Immunological assays for characterization of T-cell mediated response ELISpot assay will be performed for monitoring of T-cell mediated response against the Varicella-Zoster antigens. Diagnostic Test: Measurement of VZV- and gE-specific levels for monitoring humoral response Diagnostic Test: Frequency of natural killer cells positive for the expression of 107a after co-culture with serum and infected cells for monitoring ADCC potential
Patients with myelofibrosis treated with biologics and vaccined with Shigrix
Diagnostic Test: Immunological assays for characterization of T-cell mediated response ELISpot assay will be performed for monitoring of T-cell mediated response against the Varicella-Zoster antigens. Diagnostic Test: Measurement of VZV- and gE-specific levels for monitoring humoral response Diagnostic Test: Frequency of natural killer cells positive for the expression of 107a after co-culture with serum and infected cells for monitoring ADCC potential
Patients with psoriasis untreated with biologics and vaccined with Shigrix
Diagnostic Test: Immunological assays for characterization of T-cell mediated response ELISpot assay will be performed for monitoring of T-cell mediated response against the Varicella-Zoster antigens. Diagnostic Test: Measurement of VZV- and gE-specific levels for monitoring humoral response Diagnostic Test: Frequency of natural killer cells positive for the expression of 107a after co-culture with serum and infected cells for monitoring ADCC potential
结局指标
主要结局
Primary endpoint:
时间窗: from enrolment to up 1 year
Comparison of cell-mediated immune response at 360 days (after complete vaccination schedule) in patients with Psoriasis or Myelofibrosis treated vs untreated.
次要结局
未报告次要终点
研究者
Fausto Baldanti
Principal Investigator
Fondazione IRCCS Policlinico San Matteo di Pavia