Characterization of the immune response in immunosuppressed patients with rheumatic diseases, including to the recombinant zoster vaccine

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Toulouse

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

16 Feb 2026 → ongoing

Decision date (initial)

2025-05-28

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others

to assess the immunogenicity of the RZV vaccine (gE-specific antibody and T cell responses) in RD patients treated with JAKi (monotherapy or combined with Methotrexate) or with Methotrexate only one month after the second vaccine dose (day 90 after dose 1)

Secondary objectives 12

1. To monitor the reactogenicity profile: frequency of local (pain, swelling, redness) and systemic (fever, headache, myalgia) symptoms.
2. To measure the inflammatory responses (change in serum cytokines and gene expression) one day after each dose of RZV.
3. To assess the persistence of gE-specific antibody and T cell responses one year following vaccination with RZV.
4. To correlate the inflammatory response at day 1 after each dose with immunogenicity and/or reactogenicity.
5. To assess the function of immune cells (or “immune fitness”) at time of vaccination (by stimulating cells in vitro) and correlate with the vaccine response (immunogenicity and reactogenicity)
6. To evaluate the effect of the vaccine on the underlying rheumatologic disease during follow-up
7. To measure the functionality of antibody (e.g. ADCC, isotypes, avidity) before and after vaccination with RZV
8. To assess functional and epigenetic changes of specific innate cells, such as monocytes or NK cells, one month and 1 year after RZV vaccination compared to baseline (“trained” immunity)
9. To compare the quality of the gE-specific T cell response (e.g. memory phenotype, activation markers, transcription factors, TCR repertoire) after vaccination with RZV
10. To evaluate the memory B cell response following vaccination with RZV and changes in BCR repertoire
11. To compare the magnitude of the immune responses and inflammatory response measured after vaccination with RZV and COVID-19 mRNA vaccines in individuals who were enrolled in study “Immunogenicity of RNA-based COVID-19 vaccines in patients treated with immunosuppressive drugs – a prospective observational cohort study” (CCER ##2021-00430) to define common immune/clinical parameters associated with responsiveness to vaccines.
12. To assess the level of serum JAKi in the blood to correlate with the vaccine response. The measurement of Jaki will only be used to correlate with the vaccine response, and not used for the management of the clinical evaluation

Conditions and MedDRA coding

rheumatic disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Patients with rheumatic diseases currently with JAK-inhibitors (monotherapy or combined with Methotrexate) or with Methotrexate only and scheduled to receive the RZV vaccine
2. In stable clinical condition, as determined by the recruiting investigators
3. ≥ 18 years of age
4. Able and willing to provide informed consent

Exclusion criteria 10

1. Ongoing signs of febrile or non-febrile infection
2. Recent pregnancy with delivery in the six months preceding vaccination and/or planned pregnancy in the six months following RZV vaccination
3. Immunosuppression from the following: HIV infection; Current malignant neoplasm; primary immunodeficiency; recent (<2 years) solid or bone-marrow transplant or any transplant still requiring immunosuppressive therapy; conditions requiring medication with immunosuppressive drugs (including steroids > 5 mg/day))
4. Having received a vaccine in the last month or is expected to receive a vaccine in the next month
5. Presented with herpes zoster in the previous year
6. Hypersensitivity to the active substance or to one of the excipients
7. Pregnancy or breastfeeding (only for France)
8. Woman of childbearing age and without effective contraception throughout the duration of the study (only for France)
9. Non-affiliation to the French Social Security System. (only for France)
10. Patient under legal protection (only for France)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Geometric mean titer (GMT) of gE-specific IgG measured by ELISA at day 90
2. Mean of gE-specific CD4+ T cells expressing at least 2 markers (CD40L, IFN-gamma, IL-2, TNF-alpha) measured at day 90 per millions of T cells, measured by flow cytometry at day 90

Secondary endpoints 12

1. Frequency of self-reported clinical symptoms occurring 7 days after each vaccination
2. Increase in pro-inflammatory markers (cytokines, CRP) between day 1 and day 0 (first vaccination) and between day 60 and day 61 (second vaccination)
3. Differential expression of innate and adaptive immune response genes measured by RNA sequencing (RNAseq), with the aim to compare gene profiles before and after vaccination (day 0 vs day 1, day 60 vs day 61), differences between responses to first, second (day 1 vs day 61) or subsequent doses, and after 1 month following the vaccination
4. Kinetics of GMT of gE-specific IgG measured at day 0, 60, 90 and 360 to assess the persistence of the antibody response
5. Kinetics of gE-specific CD4+ T cells expressing at least 2 activation markers (CD40L, IFNg, IL-2, TNFa) measured at day 0, 90, and 360 to assess the persistence of the T cell responses
6. Change in disease activity evaluated at each visit using the Rheumatoid Arthritis Disease Activity Index (RADAI)(Stucki et al. 1995; Castrejón, Yazici, and Pincus 2013) for rheumatoid arthritis and psoriatic arthritis, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)(Garrett et al. 1994) for axial spondylarthritis (Appendix 2) and patient global assessment on a 0-10 scale.
7. Monitoring of episodes of shingles throughout the study period
8. ADCC (cytotoxicity), levels of isotypes, avidity levels before and after vaccination
9. Differential expression of genes and epigenetic changes of specific innate cells (monocytes or NK cells), 1 month and 1 year post vaccination (compared to before vaccination)
10. Changes in memory phenotypes, activation and transcription marker levels, TCR repertoire after RZV vaccination.
11. Differences and similarities in levels of immune and inflammatory response post RZV vaccination and COVID-19 mRNA vaccines in individuals who were enrolled in study “Immunogenicity of RNA-based COVID-19 vaccines in patients treated with immunosuppressive drugs – a prospective observational cohort study” (CCER ##2021-00430)
12. The level of JAKi will be measured by mass-spectrometry using an established and quantitative method and used to correlate with the vaccine response, including adaptive responses and reactogenicity

Investigational products

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

Test 1

Auxiliary 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Toulouse

Sponsor organisation

Centre Hospitalier Universitaire De Toulouse

Address

2 Rue Viguerie

City

Toulouse

Postcode

31300

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

principal investigator

Public contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

clinical research project manager

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 10 files

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

Application history

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