Investigating the (autoreactive) B cell compartment in antibody-mediated autoimmune diseases in comparison with the recall Tetanus Toxoid response

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Leids Universitair Medisch Centrum (LUMC)

Participant type

Healthy volunteers, Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Decision date (initial)

2025-07-08

Transition trial

No

Low-intervention

Yes

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic

To induce, by booster vaccination, the activation of TT-specific B cells in order to compare the autoreactive B cell compartment with the resting and activated TT-specific B cell compartment over time in patients with autoimmune diseases and healthy individuals.

Secondary objectives 1

1. - To compare characteristics of autoantibodies and anti-TT antibodies in plasma during different stages of activation of the underlying B cell responses - To compare the phenotype and dynamics of the TT-specific B cell response before and upon vaccination in patients versus healthy donors

Conditions and MedDRA coding

Systemic sclerosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. ≥ 18 years of age
2. able to understand the patient information form and to provide written informed consent.
3. willing to receive a single, one-time booster vaccination against tetanus toxoid.
4. having completed a primary vaccination regime against tetanus toxoid.

Exclusion criteria 8

1. who do not fulfill the classification criteria for the respective diagnoses, as set out in the inclusion criteria.
2. individuals unwilling to provide sufficient information on their current health status required to assess eligibility, with the most relevant information being the presence/absence or prior history of an autoimmune disease, vaccination history, or the current or recent use of immunosuppressive drugs.
3. for whom the treating physician considers that relevant safety issues apply (such as, for example, severe anemia) that preclude the provision of the required amount of peripheral blood projected for the study.
4. who need to donate 50 mL of blood (or more) during the first four weeks of the study for any reason other than participation in the study (such as routine clinical care, participation in another study, blood donations for the blood bank, etc.).
5. who are or have been treated with specific B cell depleting/modifying therapies (Rituximab, Belimumab, Cyclophosphamide, Tocilizumab, Abatacept) within 12 months prior to inclusion.
6. with contraindications for a booster vaccination against tetanus toxoid: o Hypersensitivity to the active substance(s) or to any of the excipients o Severe reaction after previous administration with the same vaccine
7. who received a TT vaccination or booster within the past 24 months prior to inclusion.
8. who are pregnant at the time of inclusion

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. the frequency and phenotype of antigen-specific, autoreactive B cells in the peripheral blood of patients at the indicated time-points, compared to the frequency and phenotype of TT-specific B cells prior to and upon booster vaccination, at the same timepoints. Assessment will be done by flow cytometry, generating a phenotypic profile rather than a single parameter.

Secondary endpoints 2

1. plasma levels and characteristics (e.g. glycosylation) of autoantibodies and anti-TT antibodies during different stages of activation of the underlying B cell responses.
2. phenotype and dynamics of TT-specific B cells before and upon vaccination in healthy individuals.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Leids Universitair Medisch Centrum (LUMC)

Sponsor organisation

Leids Universitair Medisch Centrum (LUMC)

Address

Albinusdreef 2

City

Leiden

Postcode

2333 ZA

Country

Netherlands

Scientific contact point

Organisation

Leids Universitair Medisch Centrum (LUMC)

Contact name

H.U. Scherer

Public contact point

Organisation

Leids Universitair Medisch Centrum (LUMC)

Contact name

Hans Ulrich Scherer

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications