Comparative Study of Two Vaccination Schedules for the Subunit Herpes Zoster Vaccine in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disease Patients Treated With Anti-CD20 Therapy: an Open-label Randomised Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 160
- 试验地点
- 24
- 主要终点
- Humoral vaccine response rate for IgG anti-VZV gE response
研究概览
简要总结
Immunocompromised individuals, such as patients with multiple sclerosis (MS) or diseases of the neuromyelitis optica spectrum (NMOSD) treated with an anti-CD20 monoclonal antibody, present an increased risk of shingles. The immunogenicity - and therefore the clinical effectiveness - of the recombinant vaccine against the varicella zoster virus based on glycoprotein E, recently recommended according to two-dose schedule two months apart in immunocompromised patients aged ≥ 18 years, could be significantly decreased when administered one month before and one month after the infusion of anti-CD20.
We hypothesize that, in patients with MS or NMOSD treated with anti-CD20 administered every six months, a two-dose M0-M6 vaccination schedule consisting of deferring the second dose six months after the first infusion, that is, five months after the anti-CD20 infusion, could improve vaccine immunogenicity and, consequently, the effectiveness of the vaccine.
详细描述
Shingles, caused by reactivation of varicella zoster virus (VZV), is a common condition in immunocompromised people. Its prevention, which has long remained a medical need unmet among these patients, was improved thanks to the availability of the recombinant glycoprotein-based VZV vaccine E (gE). Based on demonstrated clinical efficacy and safety profile in the general population as well as in immunocompromised patients, this vaccine is recommended in France according to a two-person schedule doses spaced two months apart in immunocompromised patients aged ≥ 18 years. However, further studies are needed in order to optimize vaccination strategies according to the different types of immunosuppression.
Patients with MS or NMOSD, who are at increased risk of herpes zoster, are extensively treated with anti-CD20 monoclonal antibodies, which are known to significantly alter immune responses to vaccines, in particular when vaccination is carried out early after the infusion of anti-CD20.
We hypothesize that in patients with MS or NMOSD treated with anti-CD20 administered every six months, a two-dose M0-M6 vaccination schedule, consisting of deferring the second dose to six months after the first, that is, five months after the anti-CD20 infusion, could improve vaccine immunogenicity and, consequently, the effectiveness of the vaccine.
In this phase IV randomized, controlled, open-label, parallel-group trial, we will compare, within a homogeneous population of patients with MS or NMOSD receiving antiCD20, the humoral response induced by a two-dose vaccination schedule administered at 2 months (M0-M2, "2-month" or standard group) or 6 months (M0-M6, "6-month" or experimental group). After the screening and inclusion phase, patients randomized to the M0-M2 (standard) and M0-M6 (experimental) groups will receive a first dose of recombinant herpes zoster vaccine (RZV) one month before the next scheduled infusion of anti-CD20 monoclonal antibodies (M1). The second dose of RZV will be given at either 2 months ("2-month group", M2) or 6 months ("6-month group", M6). Patients will receive their usual anti-CD20 monoclonal antibody infusions at the appropriate time M1, M7 and M13. The primary outcome will be evaluated one month after the second vaccine dose (M3 for the "2 months" group and M7 for the "6 months" group). The kinetics, intensity, and persistence of humoral and cellular immune responses, as well as safety, will be analyzed as criteria for secondary judgments during the scheduled follow-up visits until M13.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with Multiple Sclerosis (any clinical form) or Neuromyelitis optica spectrum disease seropositive for aquaporin-4 antibodies (AQP4+)
- •Aged 18 years or more
- •Treated with anti-CD20 mAbs (Rituximab IV or Ocrelizumab IV or SC) since < 2 years with dosing intervals of 6 months (and for Rituximab, treated with 1g per infusion)
- •Planned to receive the same anti-CD20 mAbs with dosing intervals of 6 months during the 13 months of the study (and for Rituximab, planned to receive 1g per infusion)
- •Known history in the medical file of varicella, or VZV IgG serology known to evidence a prior infection
- •Affiliated or beneficiary of a social security scheme
- •Written and informed consent
- •Understands and agrees to comply with the study procedures
排除标准
- •Temporary contraindication to vaccination (concurrent episode of acute fever >38.5°C)
- •Shingles in the last 12 months or VZV vaccination in the last 5 years
- •Patients already treated or supposed to be treated with Ofatumumab (another anti-CD20 mAbs but delivered with a monthly subcutaneous injection)
- •Patients who received high dose corticosteroids (methylprednisolone at a dose of ≥ 500 mg, administered over 1 to 5 days) in the 3 months prior to inclusion
- •Patients who have been exposed to Cladribine in the prior 12 months
- •Patients who received or were scheduled to receive any vaccination, except for influenza and SARS-CoV-2 vaccines during the epidemic season, within 2 weeks prior to the 2 RZV injections and up to 4 weeks after the second RZV injection
- •Hypersensitivity to the active substance or to one of the excipients
- •Patient protected by the law (guardianship, curatorship)
- •Pregnancy or breast-feeding
- •Women of childbearing potential (WOCBP) without effective contraception throughout the duration of the trial
- •Criteria related to the use of ancillary anti-CD20 treatments (Rituximab and Ocrelizumab):
- •Hypersensitivity to the active substance or to any of the excipients Severe, active infections Severe immunodeficiency Severe heart failure or severe uncontrolled heart disease Known progressive malignancies
研究组 & 干预措施
2 months arm
Patients will receive the standard vaccination schedule in two doses in 2 months.
干预措施: Two-dose M0-M2 vaccination schedule (Biological)
6 months arm
Patients will receive a vaccination schedule in two doses in 6 months.
干预措施: Two-dose M0-M6 vaccination schedule (Biological)
结局指标
主要结局
Humoral vaccine response rate for IgG anti-VZV gE response
时间窗: 3 months for the " 2 months " group and 7 months for the " 6 months " group
It will be defined as the proportion of patients with at least a 4-fold increase in anti-VZV gE antibody titers (measured by ELISA) at 1 month after the 2nd vaccine dose compared to baseline (M0), or seroconversion for those who were seronegative at M0.
次要结局
- The humoral response in terms of Geometric Mean Titer (GMT) at 1 month after the 2nd vaccine dose.(3 months for the " 2 months " group and 7 months for the " 6 months " group)
- Composite criteria of the humoral response up to M13(13 months)
- Composite criteria of the cellular response at 1 month after the 2nd vaccine dose(3 months for the " 2 months " group and 7 months for the " 6 months " group)
- Composite criteria of the cellular response at M13(13 months)
- The vaccine safety(from M0 to month 13)