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

Trial details

Who runs it

University Hospital, Toulouse

Trial code

NCT07818356EU 2025-525106-37-00

Record updated

14 September 2026

Original description

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.Read full original descriptionShow less

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.

Inclusion: 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.

Exclusion: Temporary contraindication to vaccination (concurrent episode of acute fever >38.5°C); 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; 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; Shingles in the last 12 months or VZV vaccination in the last 5 years; 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.

ClinicalTrials.gov NCT07818356 · EU CTIS 2025-525106-37-00