RECOMBINANT VARICELLA ZOSTER VIRUS GLYCOPROTEIN E for Rheumatic diseases

Inclusion criteria

• {"criterion_text":"- Patients with rheumatic diseases currently with JAK-inhibitors (monotherapy or combined with Methotrexate) or with Methotrexate only and scheduled to receive the RZV vaccine\n- In stable clinical condition, as determined by the recruiting investigators\n- ≥ 18 years of age\n- Able and willing to provide informed consent"}

Exclusion criteria

• {"criterion_text":"- Ongoing signs of febrile or non-febrile infection\n- Patient under legal protection (only for France)\n- Recent pregnancy with delivery in the six months preceding vaccination and/or planned pregnancy in the six months following RZV vaccination\n- 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))\n- Having received a vaccine in the last month or is expected to receive a vaccine in the next month\n- Presented with herpes zoster in the previous year\n- Hypersensitivity to the active substance or to one of the excipients\n- Pregnancy or breastfeeding (only for France)\n- Woman of childbearing age and without effective contraception throughout the duration of the study (only for France)\n- Non-affiliation to the French Social Security System. (only for France)"}

Primary endpoints

• {"endpoint_text":"- Geometric mean titer (GMT) of gE-specific IgG measured by ELISA at day 90","definition_or_measurement_approach":"Measured by ELISA at day 90; outcome reported as geometric mean titer (GMT) of gE-specific IgG."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Measured by flow cytometry at day 90; frequency (per million T cells) of gE-specific CD4+ T cells expressing ≥2 activation markers (CD40L, IFN-gamma, IL-2, TNF-alpha)."}

Secondary endpoints

• {"endpoint_text":"- Frequency of self-reported clinical symptoms occurring 7 days after each vaccination","definition_or_measurement_approach":"Self-reported symptom frequency collected within 7 days after each vaccination (reactogenicity)."}
• {"endpoint_text":"- Increase in pro-inflammatory markers (cytokines, CRP) between day 1 and day 0 (first vaccination) and between day 60 and day 61 (second vaccination)","definition_or_measurement_approach":"Measurement of pro-inflammatory markers (cytokines, CRP) at specified timepoints to assess change (day1 vs day0 for dose1; day61 vs day60 for dose2)."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"RNA sequencing (RNAseq) to assess differential gene expression at specified timepoints (day0 vs day1, day60 vs day61, etc.)."}
• {"endpoint_text":"- Kinetics of GMT of gE-specific IgG measured at day 0, 60, 90 and 360 to assess the persistence of the antibody response","definition_or_measurement_approach":"ELISA measurement of gE-specific IgG GMT at day0, day60, day90, and day360 to assess kinetics and persistence."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Flow cytometry measurement of gE-specific CD4+ T cells (expressing ≥2 activation markers) at day0, day90, and day360 to assess persistence."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Disease activity assessed at each visit using RADAI for RA/psoriatic arthritis, BASDAI for axial spondylarthritis, and patient global assessment (0–10)."}
• {"endpoint_text":"- Monitoring of episodes of shingles throughout the study period","definition_or_measurement_approach":"Surveillance and recording of shingles (herpes zoster) episodes during study follow-up."}
• {"endpoint_text":"- ADCC (cytotoxicity), levels of isotypes, avidity levels before and after vaccination","definition_or_measurement_approach":"Laboratory assays to measure ADCC activity, antibody isotype distribution, and avidity pre- and post-vaccination."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Gene expression and epigenetic profiling (e.g., RNAseq, epigenetic assays) of innate cells at 1 month and 1 year versus baseline."}
• {"endpoint_text":"- Changes in memory phenotypes, activation and transcription marker levels, TCR repertoire after RZV vaccination.","definition_or_measurement_approach":"Immunophenotyping and TCR repertoire analysis to assess changes in memory phenotype, activation markers, transcription factors post-vaccination."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Comparative analysis of immune/inflammatory responses between RZV-vaccinated participants and individuals from prior COVID-19 mRNA vaccine cohort study."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Quantitative mass-spectrometry measurement of serum JAK inhibitor levels to correlate with immunogenicity and reactogenicity outcomes."}

France

Earliest CTIS Part Ii Submission Date

28-04-2025

Latest Decision Or Authorization Date

04-09-2025

Processing Time Days

129

Number Of Sites

2

Number Of Participants

60

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Toulouse

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France