Clinical trial NCT05019248: Immune Response to Seasonal Influenza Vaccination in Multiple Sclerosis Patients Receiving Cladribine
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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Multiple Sclerosis, Relapsing-Remitting
Vaccine Response Impaired
Keywords: influenza vaccination
cladribine
Lead sponsor: Heinrich-Heine University, Duesseldorf
Sponsor class: OTHER
First posted: 2021-08-24
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 52 patients per group/cohort, resulting in a theoretical maximum number of 260 patients. Patients will be screened until this number is reached.

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.


Eligibility criteria: 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

Primary outcomes:
measure: Proportion who achieve seroprotection
timeFrame: 6 months
Secondary outcomes:
measure: Fraction with 2-fold increase of HI titers
timeFrame: 6 months
measure: Fraction with 4-fold increase of HI titers
timeFrame: 6 months
measure: Seroconversion rate
timeFrame: 6 months
measure: Mean antibody titers
timeFrame: 6 months
measure: Cellular immune responses
timeFrame: 6 months
measure: Serum immunoglobulin subtypes
timeFrame: 6 months
measure: Influenza infections
timeFrame: 6 months
Other outcomes:
Locations:
city: Duesseldorf
country: Germany
facility: Medical Faculty, Heinrich-Heine-University
state: Northrhine-Westphalia
Study officials:
affiliation: Heinrich-Heine-University Duesseldorf, Germany
name: Sven G Meuth, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: