MSHINGVAX: Immunogenicity of the Recombinant Zoster Vaccine in Multiple Sclerosis Patients

Sponsor

Prof Patrice Lalive (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05596526

Collaborator

(none)

100

Enrollment

Location

Arms

Anticipated Duration (Months)

4.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Shingles Zoster	Biological: recombinant zoster vaccine	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Nov 1, 2022

Anticipated Primary Completion Date :

Nov 1, 2024

Anticipated Study Completion Date :

Nov 1, 2024

Arms and Interventions

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®

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®

Outcome Measures

Primary Outcome Measures

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

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 -pIMDs [day 360]
Incidence of potential immune mediated disorders (pIMDs) 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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.