Multiple Sclerosis, Relapsing-Remitting, Vaccine Response Impaired
Conditions
Keywords
influenza vaccination, cladribine
Brief 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.
Interventions
BIOLOGICALMost 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)).
Sponsors
Heinrich-Heine University, Duesseldorf
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion who achieve seroprotection | 6 months | 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)). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fraction with 4-fold increase of HI titers | 6 months | Proportion of patients who achieve a 4-fold increase in specific HI titers at 6 months post-immunization |
| Seroconversion rate | 6 months | Proportion of patients with seroconversion (i.e., a pre-vaccination antibody titer \< 10 and a post-vaccination HI titer \> 40) |
| Mean antibody titers | 6 months | Geometric mean antibody titers (GMTs) and geometric mean antibody ratios (GMRs, post-vaccination:pre-vaccination) prior and 6 months after vaccination |
| Fraction with 2-fold increase of HI titers | 6 months | Proportion of patients who achieve a 2-fold increase in specific HI titers at 6 to 8 months post-immunization |
| Serum immunoglobulin subtypes | 6 months | Analysis of quantitative Ig levels (including total Ig, IgG, IgG subtypes, IgM, and IgA) |
| Influenza infections | 6 months | Incidence of infections caused by influenza |
| Cellular immune responses | 6 months | 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 |
Countries
Germany
Contacts
Primary ContactSven G Meuth, MD, PhD
Backup ContactLeoni Rolfes, MD
Outcome results
None listed