The Role of IL-23 in Chronic Inflammatory Disease: Exploring the Cellular and Molecular Targets of IL-23 Signaling in Peripheral and Axial Spondyloarthritis

Spondyloarthritis Clinical Trial

— SpA23  

Official title:

The Role of IL-23 in Chronic Inflammatory Disease: Exploring the Cellular and Molecular Targets of IL-23 Signaling in Peripheral and Axial Spondyloarthritis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05290363
• Other study ID #: 2021-087
• Secondary ID: 2021-A02801-40
• Status: Recruiting
• Phase: N/A
• Start date: October 6, 2022
• Est. completion date: March 15, 2026

Study information

• Verified date: April 2024
• Source: Institut Pasteur
• Contact: Lars ROGGE, Dr
• Phone: +33140613822
• Email: lars.rogge[@]pasteur.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a research study involving humans, of the interventional type with minimal risks and constraints (RIPH2). It is a bicentric, non randomized prospective study aiming to better understand the mechanisms of the response to anti-IL-23 biologics in Spondyloarthritis patients attending the rheumatology department of hospital Cochin and Saint Antoine (APHP).

Description:

The aim of this project is to improve our understanding of the role of IL-23 in the pathophysiology of axial SpA and peripheral SpA. This objective is detailed in three specific aims: 1. Define the effects of IL-23 on gene expression and cytokine production in innate and adaptive T lymphocytes from patients with SpA, and correlate them with the patient's genotype; 2. Phenotypically characterize immune cell populations in peripheral blood and in synovial fluid from peripheral SpA patients and identify at the single cell level the cells expressing the IL-23 receptor and/or producing IL-17. The study population to be included are patients affected by SpA, attended to in the Rheumatology Departments of Cochin Hospital or of Saint Antoine Hospital in Paris. Participants will be divided into two groups: Group 1 comprises patients diagnosed with axial SpA, Group 2 SpA patients with peripheral SpA

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: March 15, 2026
• Est. primary completion date: March 15, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age : Adults (>18 years)
• Satisfying ASAS diagnostic criteria for SpA
• Patient has active disease, defined by the presence of active synovitis, tendinitis, or dactylitis or significant inflammatory pain of the spine, judged by the examining clinician to be due to SpA.
• Informed consent signed
• Beneficiary of health insurance, except for the AME Only for patients of Group 1
• Patient is naïve to biological therapies Only for patients of Group 2
• Patient is affected by peripheral SpA (ASAS criteria), with inflammation of peripheral joints
• Patient requires aspiration, as part of standard care
• Patient is naïve of biological treatment, or has been treated with one biologic, with a wash-out period of at least 3 months before inclusion

Non inclusion criteria:

• Patient is minor
• Patient is pregnant or breastfeeding
• Patient is immunocompromised
• Patient has received biological therapy with 2 or more biologics
• Patient is receiving corticosteroid treatment > 10 mg per day
• Patient is under legal protection, curators, guardianship
• Patient refuses consent
• Previous history of alcoholism, drug addiction, psychological problems, severe concomitant conditions that could invalidate the patient's consent or limit the patient's compliance to the treatment protocol.
• Beneficiary of the AME Only for group 1 • Patient has received biological therapy Only for group 2
• Patient has received biological therapy, with a wash-out period of less than 3 months

Related Conditions & MeSH terms

• Axial Spondyloarthritis
• Spondylarthritis
• Spondylitis
• Spondyloarthritis

Intervention

Other:
• Blood sampling
A 51 mL blood sample will be collected during the study
• synovial aspiration
If synovial aspiration is required in standard care for patients with peripheral spondylarthritis. Medical waste product will be collected for the study

Locations

Country	Name	City	State
France	Lars ROGGE	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Institut Pasteur	Janssen Biotech, Inc.

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Profiling of open chromatin regions	Profiling of open chromatin regions (ATAC seq) in T lymphocytes, cultured in the presence or absence of IL-23in order to define the effects of IL-23 on gene expression and cytokine production in innate and adaptive T lymphocytes from patients with SpA, and correlate them with the patient's genotype	4 years
Primary	Profiling of transcriptome	Profiling of the transcriptome (RNA-seq) in T lymphocytes, cultured in the presence or absence of IL-23in order to define the effects of IL-23 on gene expression and cytokine production in innate and adaptive T lymphocytes from patients with SpA, and correlate them with the patient's genotype	4 years
Primary	Profiling of the genome	Profiling of the genome (genotyping) in T lymphocytes, cultured in the presence or absence of IL-23in order to define the effects of IL-23 on gene expression and cytokine production in innate and adaptive T lymphocytes from patients with SpA, and correlate them with the patient's genotype	4 years
Primary	Profiling of cytokine expression	Profiling of cytokine expression (Proximity Extension Assay technology) in T lymphocytes, cultured in the presence or absence of IL-23 in order to define the effects of IL-23 on gene expression and cytokine production in innate and adaptive T lymphocytes from patients with SpA, and correlate them with the patient's genotype	4 years
Primary	Single cell transcriptome analysis	Single cell transcriptome analysis of cells from patients with peripheral SpA will be performed to characterize immune cell populations in peripheral blood and in synovial fluid and identify at the single cell level the cells expressing the IL-23 receptor and/or producing IL-17;	4 years
Secondary	Measure lymphocyte levels to explore the effects of anti-IL23 treatment on the immune responses of axSpA patients	Define the effects in vitro of IL-23 blockade on immune responses in the peripheral blood of axSpA patients, using whole blood culture assays to profile stimulated protein secretion and gene expression, in the presence or absence of IL-23 inhibitors.; As this therapy is not employed for the treatment of axSpA, we will characterize the in vitro effects of anti-IL-23 blockade on the immune responses of patients with axSpA, by analysing gene expression and protein secretion in whole blood cultures in the presence or absence of anti-IL-23 treatment.; We will isolate MAIT, ?d TCR+, CD4+CCR6+ and CD8+CCR6+ (enriched in IL-23R+) T cell populations from peripheral blood of psoriasis patients and stimulate them through the T cell receptor (TCR), in the presence or absence of IL-23.	4 years