Immunogenicity of the Recombinant Zoster Vaccine in Multiple Sclerosis Patients

Study Overview
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Brief Summary
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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
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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)

Official Title
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Immunogenicity of the Recombinant Zoster Vaccine (Shingrix ®) in Multiple Sclerosis Patients Treated With Anti-CD20 Antibodies Compared to Controls- a Phase IV Monocentric Study

Conditions
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Shingles, Zoster

Intervention / Treatment
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* Biological: recombinant zoster vaccine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MS patients on anti-CD20<br>Participants aged 18 and above will receive two doses of the recombinant Zoster vaccine (Shingrix®) | Biological: recombinant zoster vaccine<br>* Shingrix® vaccine will be administered in two vaccinations on Day0 and Day60<br>* Other names: Shingrix®;|
| Experimental: Healthy controls<br>Healthy participants aged 50 to 59 will receive two doses of the recombinant Zoster vaccine (Shingrix®) | Biological: recombinant zoster vaccine<br>* Shingrix® vaccine will be administered in two vaccinations on Day0 and Day60<br>* Other names: Shingrix®;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vaccine safety - AESI 7 days | Incidence adverse events of special interest (AESI) in the 7 days following each vaccination (reactogenicity) collected in a diary card | 7 days | 
| Vaccine safety - SAE 360 days | Incidence of serious adverse events (SAE) throughout the study period | day 360 | 
| Vaccine safety -pIMDs | Incidence of potential immune mediated disorders (pIMDs) throughout the study period | day 360 | 
| Vaccine safety-relapse in MS patients | 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 | day 90 | 
| Vaccine immunogenicity - CD4+ T cells per million of T cells, measured at D90 | 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 | Day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RZV vaccine, Multiple Sclerosis, Immune response, Safety