Immune Response to Seasonal Influenza Vaccination in Multiple Sclerosis Patients Receiving Cladribine

Multiple Sclerosis, Relapsing-Remitting Clinical Trial

— CIRMS  

Official title:

A Non-interventional Observation Study to Evaluate Immune Responses Following Seasonal Influenza Vaccine in Participants With Relapsing Multiple Sclerosis Treated With Cladribine Tablets

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05019248
• Other study ID #: 2021-1474
• Status: Recruiting
• Start date: September 1, 2020
• Est. completion date: April 30, 2022

Study information

• Verified date: August 2021
• Source: Heinrich-Heine University, Duesseldorf
• Contact: Sven G Meuth, MD, PhD
• Phone: 0049 211 81 19532
• Email: svenguenther.meuth[@]med.uni-duesseldorf.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The primary objective of this study is to characterize the antibody response to seasonal influenza vaccine, in patients with active RRMS, treated with cladribine, compared to control individuals with basic immunomodulatory treatment. Serum antibody titers against the respective pathogen will be assessed prior to and 6 to 8 months following vaccination.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 260
• Est. completion date: April 30, 2022
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. Signed informed consent form (ICF)

2. Age 18 to 60 years old (inclusive) as of the date the ICF is signed

3. Diagnosis of RRMS according to the revised McDonald criteria

4. EDSS score of 0.0 to 7.0 (inclusive)

5. In case of participants who are subjected to influenza vaccination by the treating physicians prior to cladribine the first or second cycle of cladribine (cohort 1 + cohort 3), this should be performed at least 4 to 6 weeks before the start of cladribine.

Definition of control group:

Patients with active RRMS treated with cladribine will be compared to sex and age matched control individuals, with RRMS under basic treatment either with interferon beta, glatiramer acetate, dimethyl fumarate or teriflunomide, who provide sample material prior to and 6 to 8 months after routine seasonal influenza vaccination during the same period.

Exclusion Criteria:

1. Previous treatment with B-cell targeted therapies (e.g., rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab)

2. Any previous treatment with alemtuzumab, cladribine, cyclophosphamide, mitoxantrone, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, total body irradiation, or bone marrow transplantation

3. Medical, psychiatric, cognitive, or other conditions that, in the investigator's opinion, compromise the patient's ability to understand the patient information, to give informed consent, or to complete the study

4. Patients that receive immunosuppressive treatment for diseases other than MS or that receive long-term corticosteroid treatment

5. Patients that received apheresis procedures 6 weeks prior to vaccination or in-between vaccination and DMT initiation

6. Systemic high dose corticosteroid therapy within 6 weeks prior to vaccination or in-between vaccination and DMT initiation

7. Patients with verified infection by human-immunodeficiency-virus or hepatitis-c-virus

8. Patients with major impairment of the blood coagulation system including therapy with anticoagulants

9. Patients with known chicken egg allergy

Related Conditions & MeSH terms

• Influenza, Human
• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis
• Vaccine Response Impaired

Intervention

Biological:
• Most recent vaccine to seasonal influenza
Seasonal Influenza vaccine: according to the latest SmPC and according to national guidelines (published by the Standing Committee on Vaccination (STIKO)).

Locations

Country	Name	City	State
Germany	Medical Faculty, Heinrich-Heine-University	Duesseldorf	Northrhine-Westphalia

Sponsors (1)

Lead Sponsor	Collaborator
Heinrich-Heine University, Duesseldorf

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion who achieve seroprotection	The capacity of influenza vaccine to elicit a measurable immune response (immunogenicity) when it is administered (i) shortly (at least 4-6 weeks) before cladribine initiation (cohort 1), (ii) 3 to 4 months after cladribine initiation (cohort 2) (iii) shortly (at least 4-6 weeks) before second cladribine administration (cohort 3) and (iv) in patients who have already received the second cycle of cladribine tablets (3 to 4 months after second cycle; cohort 4), compared to RRMS patients treated with basic DMTs (cohort 5). Efficacy is measured as proportion of patients who achieve seroprotection (specific hemagglutination inhibition (HI) titers > 1:40)).	6 months
Secondary	Fraction with 2-fold increase of HI titers	Proportion of patients who achieve a 2-fold increase in specific HI titers at 6 to 8 months post-immunization	6 months
Secondary	Fraction with 4-fold increase of HI titers	Proportion of patients who achieve a 4-fold increase in specific HI titers at 6 months post-immunization	6 months
Secondary	Seroconversion rate	Proportion of patients with seroconversion (i.e., a pre-vaccination antibody titer < 10 and a post-vaccination HI titer > 40)	6 months
Secondary	Mean antibody titers	Geometric mean antibody titers (GMTs) and geometric mean antibody ratios (GMRs, post-vaccination:pre-vaccination) prior and 6 months after vaccination	6 months
Secondary	Cellular immune responses	Flow cytometry analysis, which will include (but is not limited to) the following cells: Total B cells (CD19 positive), B-cell subsets, e.g., memory B cells, naïve B cells, plasma cells; Total T cell (CD3 positive) and T cell subsets, e.g. T helper cells, cytotoxic lymphocyte T cells	6 months
Secondary	Serum immunoglobulin subtypes	Analysis of quantitative Ig levels (including total Ig, IgG, IgG subtypes, IgM, and IgA)	6 months
Secondary	Influenza infections	Incidence of infections caused by influenza	6 months