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
- 招募中
- 入组人数
- 160
- 试验地点
- 24
- 主要终点
- Humoral Vaccine Response Rate (VRR) measured 1 month after the 2nd vaccine dose (M3 for the “2 months” group and M7 for the “6 months” group), defined as the proportion of patients with at least a 4-fold increase in anti-VZV gE antibody titers (measured by ELISA) compared to baseline (M0), or seroconversion for those who were seronegative at M0.
研究概览
简要总结
To compare, in MS and NMOSD patients receiving anti-CD20 mAbs IV or SC every 6 months, the humoral response elicited by a 2-dose RZV vaccine scheduled 2 (M0-M2, “2 months group”, the standard group) or 6 months (M0-M6, “6 months group”, the experimental group) apart and measured 1 month after the second dose. The first dose will be administered 1 month prior to the anti CD20 infusion, and the second either 1 (“2 months group”) or 5 months (“6 months group”) after.
入排标准
- 年龄范围
- 18 years 至 64 years（18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Patients with MS (any clinical form) or NMOSD 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)
- •Pregnancy or breast-feeding
- •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
- •Women of childbearing potential (WOCBP) without effective contraception throughout the duration of the trial
- •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)
研究组 & 干预措施
RITUXIMAB
干预措施: RITUXIMAB (Drug)
OCRELIZUMAB
干预措施: OCRELIZUMAB (Drug)
Shingrix suspension for injection in pre-filled syringe Herpes zoster vaccine (recombinant, adjuvanted)
干预措施: Shingrix suspension for injection in pre-filled syringe Herpes zoster vaccine (recombinant, adjuvanted) (Drug)
结局指标
主要结局
Humoral Vaccine Response Rate (VRR) measured 1 month after the 2nd vaccine dose (M3 for the “2 months” group and M7 for the “6 months” group), defined as the proportion of patients with at least a 4-fold increase in anti-VZV gE antibody titers (measured by ELISA) compared to baseline (M0), or seroconversion for those who were seronegative at M0.
Humoral Vaccine Response Rate (VRR) measured 1 month after the 2nd vaccine dose (M3 for the “2 months” group and M7 for the “6 months” group), defined as the proportion of patients with at least a 4-fold increase in anti-VZV gE antibody titers (measured by ELISA) compared to baseline (M0), or seroconversion for those who were seronegative at M0.
次要结局
- Ratio (M0-M6 versus M0-M2 groups) of the adjusted Geometric Mean Titer (GMT) of anti-VZV gE IgG at 1 month after the 2nd vaccine dose.
- 2. Geometric Mean Titer (GMT) of anti-VZV gE IgG measured at baseline (M0) and up to M13: before the 2nd vaccine dose, 1 month after the 2nd vaccine dose, and prior to the next anti CD20 infusions: M7 and M13.
- 3. Humoral VRR at M13
- 4. Cellular VRR for gE-specific CD4[AIM+] T response measured 1 month after the 2nd vaccine dose.
- Proportion of gE-specific CD4[AIM+] T cells among CD4 T cells measured at baseline (M0) and up to M13: before the 2nd vaccine dose, 1 month after the 2nd vaccine dose, and prior to the next anti-CD20 infusions: M7 and M13.
- Cellular VRR measured at M13.
- Adverse Events
研究者
Jonathan CIRON
Scientific
Centre Hospitalier Universitaire De Toulouse