Immunogenicity of the Recombinant Zoster Vaccine in Multiple Sclerosis Patients (MSHINGVAX)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Zoster; Shingles
• Intervention / Treatment: Biological: recombinant zoster vaccine

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 Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Arnaud Didierlaurent, Pr; Phone Number: +41 22 37 95781; Email: arnaud.didierlaurent@hcuge.ch
• Study Contact Backup: Name: Patrice Lalive, Pr; Phone Number: +41 22 3728318; Email: patrice.lalive@hcuge.ch

Study Locations

• Switzerland
  • Geneva,, Switzerland, 1205
    • Recruiting
    • University Hospitals of Geneva
    • Contact: Arnaud Didierlaurent, Phd; Phone Number: +41 22 37 95781; Email: arnaud.didierlaurent@unige.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Prof Patrice Lalive
• Investigators: Principal Investigator: Patrice Lalive, Pr, University Hospitals of Geneva; Study Director: Arnaud Didierlaurent, Pr, University Hospitals of Geneva

Publications and helpful links

Helpful Links

• Shingrix vaccine information

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2022
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: October 24, 2022
• First Submitted That Met QC Criteria: October 24, 2022
• First Posted (Actual): October 27, 2022

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; Safety; Immune response; RZV vaccine
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Virus Diseases; Infections; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; DNA Virus Infections; Herpesviridae Infections; Varicella Zoster Virus Infection; Multiple Sclerosis; Sclerosis; Herpes Zoster
• Other Study ID Numbers: 2022-01255

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No