Immunogenicity of the Recombinant Zoster Vaccine in Multiple Sclerosis Patients

Phase 4

Recruiting

• Conditions: Shingles; Zoster
• Interventions: Biological: recombinant zoster vaccine

• Registration Number: NCT05596526
• Lead Sponsor: Prof Patrice Lalive

Brief Summary

The purpose of this study is to provide evidence as to whether RZV is immunogenic with an acceptable safety profile in Multiple Sclerosis patients on anti-CD20 treatment.

Detailed Description

In this monocentric study, we will assess the immunogenicity and safety of two doses of the adjuvanted recombinant Zoster vaccine (RZV, or Shingrix®) in Multiple sclerosis patients treated with anti-CD20 (ocrelizumab, group 1) compared to healthy controls (group 2).

Participants will receive Shingrix® on Day0 and Day60; immunological response will be assessed on Day 0, 1, Day 60, 61, Day90 and Day360.

Unsolicited Adverse events of special interest (AESI) will be collected throughout the study period; patients reported outcomes (PROs) will be declared for one week after each vaccination. Safety of MS patients will be monitored through EDSS scoring and MRI before and 1 month after vaccination (D90) and at day 180 and 360 (EDSS scoring only)

Study Timeline

• Study First Submitted: 2022-10-24
• Study First Submitted QC: 2022-10-24
• Study First Posted: 2022-10-27
• Study Start: 2022-12-01
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-08
• Last Update Posted: 2024-04-10
• Primary Completion: 2024-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

For MS patients:

• 18 years and above
• Diagnosed with relapsing MS according to McDonald Criteria (2017)
• Not already vaccinated by RZV and willing to be vaccinated with RZV.
• At least 1 year on anti-CD20 treatment: 2 initial infusions of Ocrelizumab 300 mg (2 weeks apart), one infusion of Ocrelizumab 600 mg 6 months apart, one infusion of Ocrelizumab 600 mg 12 months after initial infusions
• Informed consent as documented by signature

For healthy controls

• Aged 50 to 59
• Not already vaccinated by RZV and willing to be vaccinated with RZV
• Informed consent as documented by signature

Exclusion Criteria

• Recent MS relapse in the 6 weeks preceding planned vaccination
• Ongoing signs of febrile or non-febrile infection at the time of vaccination
• Recent pregnancy with delivery in the six months preceding vaccination and/or planned pregnancy in the six months following RZV vaccination
• Immunosuppression from the following: HIV infection, current active systemic auto-immune disease (other than MS), current malignant neoplasm; primary immunodeficiency; recent solid or bone-marrow transplant or any transplant still requiring immunosuppressive therapy; conditions requiring medication with immunosuppressive drugs
• Having received a vaccine in the last month
• Having received a shingles vaccine within one year
• Presented with herpes zoster in the previous year
• Contra-indication to RZV
• Unable to provide informed consent or inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia.
• Participation in another study with investigational drug within the 30 days preceding and during the present study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Healthy controls	recombinant zoster vaccine	Healthy participants aged 50 to 59 will receive two doses of the recombinant Zoster vaccine (Shingrix®)
MS patients on anti-CD20	recombinant zoster vaccine	Participants aged 18 and above will receive two doses of the recombinant Zoster vaccine (Shingrix®)

Primary Outcome Measures

Name	Time	Method
Geometric mean titer (GMT) of glycoprotein E (gE)-specific total IgG	day 90	gE-specific total Immunoglobulin(Ig)G titers is determined by gE-specific ELISA from sera samples

Secondary Outcome Measures

Name	Time	Method
Vaccine safety -pIMDs	day 360	Incidence of potential immune mediated disorders (pIMDs) throughout the study period
Vaccine safety - AESI 7 days	7 days	Incidence adverse events of special interest (AESI) in the 7 days following each vaccination (reactogenicity) collected in a diary card
Vaccine safety - SAE 360 days	day 360	Incidence of serious adverse events (SAE) throughout the study period
Vaccine safety-relapse in MS patients	day 90	Incidence of relapse in MS patients during a follow-up of 3 months after the first dose (d90) compared to the year preceding vaccination with RZV
Vaccine immunogenicity - CD4+ T cells per million of T cells, measured at D90	Day 90	Mean of gE-specific CD4+ T cells expressing at least 2 activation markers (i.e. CD40 ligand, interferon-gamma, IL-2 or TNF-alpha) per million of T cells, measured at D90

Trial Locations

Locations (1)

University Hospitals of Geneva; 🇨🇭 Geneva,, Switzerland