Multiple Sclerosis, Relapsing-RemittingCIRMSNCT05019248
Immune Response to Seasonal Influenza Vaccination in Multiple Sclerosis Patients Receiving Cladribine
An observational study of Multiple Sclerosis, Relapsing-Remitting and Vaccine Response Impaired, run by Heinrich-Heine University, Duesseldorf at 1 site in Germany.
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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Multiple Sclerosis, Relapsing-Remitting, Vaccine Response Impaired
- What is being tested?
- Most recent vaccine to seasonal influenza
- Type of treatment
- Vaccines
- How many people
- 260 participants
- Where
- 1 siteGermany
- Study dates
- 1 Sep 2020to 30 Apr 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
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.
Who may be able to join
- 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.
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
Medical Faculty, Heinrich-Heine-University
Düsseldorf, North Rhine-Westphalia, 40225
Leoni Rolfes, MD, 0049 211 81 19532, leoni.rolfes@med.uni-duesseldorf.de
About this study
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
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.
- Being tested
- Most recent vaccine to seasonal influenza
- Keywords
- influenza vaccination, cladribine
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting, Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Most recent vaccine to seasonal influenzaBiological
Seasonal Influenza vaccine: according to the latest SmPC and according to national guidelines (published by the Standing Committee on Vaccination (STIKO)).
| Study group | Role | What they receive |
|---|---|---|
| vaccination prior to first cladribine exposition | Not described Receives: Biological: Most recent vaccine to seasonal influenza | |
| vaccination shortly after first cladribine exposition | Not described Receives: Biological: Most recent vaccine to seasonal influenza | |
| vaccination prior to second cladribine exposition | Not described Receives: Biological: Most recent vaccine to seasonal influenza | |
| vaccination following completion of cladribine treatment | Not described Receives: Biological: Most recent vaccine to seasonal influenza | |
| vaccination in patients with RRMS not subjected to cladribine | Not described Receives: Biological: Most recent vaccine to seasonal influenza |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)).
Measured: 6 months
Secondary outcomes (7)
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
Measured: 6 months
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
Measured: 6 months
Seroconversion rate
Proportion of patients with seroconversion (i.e., a pre-vaccination antibody titer < 10 and a post-vaccination HI titer > 40)
Measured: 6 months
Mean antibody titers
Geometric mean antibody titers (GMTs) and geometric mean antibody ratios (GMRs, post-vaccination:pre-vaccination) prior and 6 months after vaccination
Measured: 6 months
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
Measured: 6 months
Serum immunoglobulin subtypes
Analysis of quantitative Ig levels (including total Ig, IgG, IgG subtypes, IgM, and IgA)
Measured: 6 months
Influenza infections
Incidence of infections caused by influenza
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2021
- Study start1 Sep 2020
- Primary completion31 Dec 2021 (estimated)
- Study completion30 Apr 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple Sclerosis, Relapsing-RemittingStudies of the same condition, open and under way.
- More trials run by Heinrich-Heine University, DuesseldorfThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 260 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Heinrich-Heine University, Duesseldorf
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sven G Meuth, MD, PhD, Principal investigator, Heinrich-Heine-University Duesseldorf, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05019248
- Sponsor's protocol ID
- 2021-1474
- Acronym
- CIRMS
- Status last verified
- Aug 2021
- First submitted
- 19 Aug 2021
- Last updated
- 24 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 37174643
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05019248
- Acronym / sponsor ID
- CIRMS / 2021-1474
- Keywords
- influenza vaccination, cladribine
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 260 participants (estimated)
- Lead sponsor
- Heinrich-Heine University, DuesseldorfUniversity, hospital or other
- Study start
- 1 Sep 2020 (actual)
- Primary completion
- 31 Dec 2021 (estimated)
- Study completion
- 30 Apr 2022 (estimated)
- First posted
- 24 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- 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.
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Most recent vaccine to seasonal influenzaSeasonal Influenza vaccine: according to the latest SmPC and according to national guidelines (published by the Standing Committee on Vaccination (STIKO)). | Biological | 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 |
Primary outcome
Proportion who achieve seroprotection
Time frame: 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)).
7 secondary outcomes
Fraction with 2-fold increase of HI titers
Time frame: 6 months
Fraction with 4-fold increase of HI titers
Time frame: 6 months
Seroconversion rate
Time frame: 6 months
Mean antibody titers
Time frame: 6 months
Cellular immune responses
Time frame: 6 months
Serum immunoglobulin subtypes
Time frame: 6 months
Influenza infections
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2021.
- Derived from this study: PubMed 37174643Rolfes 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.
- Individual participant dataSharing planned: No
Related trials for Multiple Sclerosis, Relapsing-Remitting
Active, not recruiting
Myrosinase Bioactivated Gglucoraphanin for the Treatment of Neurodegenerative Diseases (GRA-MYR-ND)
PARKINSON DISEASE (Disorder), Multiple Sclerosis (MS) - Relapsing-remitting
Recruiting
Wearable Focal Vibration Therapy on Upper Extremity Function of People With Multiple Sclerosis: A Pilot Study
Multiple Sclerosis (MS) - Relapsing-remitting, Upper Extremity Dysfunction
Not yet recruiting
Treatment of Memory Retrieval Impairments in MS With HDtDCS to the LIFG in a Placebo Controlled Trial
Multiple Sclerosis, Relapsing-remitting Multiple Sclerosis (RRMS)
Recruiting
Monthly Monitoring of Plasma NfL in Treated Relapsing-remitting Multiple Sclerosis to Detect Persistent Infraclinical Disease Activity
Multiple Sclerosis (MS) - Relapsing-remitting
Active, not recruitingPhase 4
Safety and Efficacy Study of Fingolimod in Taiwanese Adults (≥ 20years) With Relapsing Remitting Multiple Sclerosis
Multiple Sclerosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sven G Meuth, MD, PhD principal investigator
Heinrich-Heine-University Duesseldorf, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Multiple Sclerosis, Relapsing-Remitting and Vaccine Response Impaired, run by Heinrich-Heine University, Duesseldorf at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sven G Meuth, MD, PhD (0049 211 81 19532, svenguenther.meuth@med.uni-duesseldorf.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion who achieve seroprotection (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05019248, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2021.