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

NCT05019248 | Unknown FDA Drug

• 1 other identifier: 2021-1474
• Study Type: observational
• Target: 260
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Sclerosis, Relapsing-Remitting; Vaccine Response Impaired

Keywords

influenza vaccination; cladribine

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Fraction with 2-fold increase of HI titers

  6 months

• Fraction with 4-fold increase of HI titers

  6 months

• Seroconversion rate

  6 months

• Mean antibody titers

  6 months

• Cellular immune responses

  6 months

Study Arms (5)

vaccination prior to first cladribine exposition

Biological: Most recent vaccine to seasonal influenza

vaccination shortly after first cladribine exposition

Biological: Most recent vaccine to seasonal influenza

vaccination prior to second cladribine exposition

Biological: Most recent vaccine to seasonal influenza

vaccination following completion of cladribine treatment

Biological: Most recent vaccine to seasonal influenza

vaccination in patients with RRMS not subjected to cladribine

Biological: Most recent vaccine to seasonal influenza

Interventions

Most recent vaccine to seasonal influenza BIOLOGICAL

Seasonal Influenza vaccine: according to the latest SmPC and according to national guidelines (published by the Standing Committee on Vaccination (STIKO)).

vaccination following completion of cladribine treatment; vaccination in patients with RRMS not subjected to cladribine; vaccination prior to first cladribine exposition; vaccination prior to second cladribine exposition; vaccination shortly after first cladribine exposition

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• 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.

You may qualify if:

• Signed informed consent form (ICF)
• Age 18 to 60 years old (inclusive) as of the date the ICF is signed
• Diagnosis of RRMS according to the revised McDonald criteria
• EDSS score of 0.0 to 7.0 (inclusive)
• 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.

You may not qualify if:

• Previous treatment with B-cell targeted therapies (e.g., rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab)
• Any previous treatment with alemtuzumab, cladribine, cyclophosphamide, mitoxantrone, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, total body irradiation, or bone marrow transplantation
• 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
• Patients that receive immunosuppressive treatment for diseases other than MS or that receive long-term corticosteroid treatment
• Patients that received apheresis procedures 6 weeks prior to vaccination or in-between vaccination and DMT initiation
• Systemic high dose corticosteroid therapy within 6 weeks prior to vaccination or in-between vaccination and DMT initiation
• Patients with verified infection by human-immunodeficiency-virus or hepatitis-c-virus
• Patients with major impairment of the blood coagulation system including therapy with anticoagulants
• Patients with known chicken egg allergy

Sponsors & Collaborators

• Heinrich-Heine University, Duesseldorf: lead

Study Sites (1)

Medical Faculty, Heinrich-Heine-University

Düsseldorf, North Rhine-Westphalia, 40225, Germany

RECRUITING

Related Publications (1)

• Rolfes L, Pfeuffer S, Skuljec J, He X, Su C, Oezalp SH, Pawlitzki M, Ruck T, Korsen M, Kleinschnitz K, Aslan D, Hagenacker T, Kleinschnitz C, Meuth SG, Pul R. Immune Response to Seasonal Influenza Vaccination in Multiple Sclerosis Patients Receiving Cladribine. Cells. 2023 Apr 25;12(9):1243. doi: 10.3390/cells12091243.

  PMID: 37174643 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

(I) Serum samples for assessment of antibody levels (II) Peripheral blood mononuclear cells for assessment of cellular immune responses

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Influenza, Human

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Study Officials

• Sven G Meuth, MD, PhD

  Heinrich-Heine-University Duesseldorf, Germany

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sven G Meuth, MD, PhD

CONTACT

0049 211 81 19532; svenguenther.meuth@med.uni-duesseldorf.de

Leoni Rolfes, MD

CONTACT

0049 211 81 19532; leoni.rolfes@med.uni-duesseldorf.de

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2021
• First Posted: August 24, 2021
• Study Start: September 1, 2020
• Primary Completion: December 31, 2021
• Study Completion: April 30, 2022
• Last Updated: August 24, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)