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The Role of IL-23 in Chronic Inflammatory Disease: Exploring the Cellular and Molecular Targets of IL-23 Signaling in Peripheral and Axial Spondyloarthritis (SpA23)

Primary Purpose

Spondyloarthritis

Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Blood sampling
synovial aspiration
Sponsored by
Institut Pasteur
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Spondyloarthritis focused on measuring interleukin-23, anti-IL-23 therapy, immune response, Spondyloarthritis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Lars ROGGERecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Patients with axial spondyloarthritis participating in the study

Patients with peripheral spondyloarthritis participating in the study

Arm Description

People with axial spondylarthritis (60 participants),

People with peripheral spondylarthritis (30 participants).

Outcomes

Primary Outcome Measures

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
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
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
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
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;

Secondary Outcome Measures

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, γδ 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.

Full Information

First Posted
February 25, 2022
Last Updated
March 9, 2023
Sponsor
Institut Pasteur
Collaborators
Janssen Biotech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05290363
Brief 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
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 6, 2022 (Actual)
Primary Completion Date
March 15, 2026 (Anticipated)
Study Completion Date
March 15, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut Pasteur
Collaborators
Janssen Biotech, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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).
Detailed 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: 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; 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spondyloarthritis
Keywords
interleukin-23, anti-IL-23 therapy, immune response, Spondyloarthritis

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Two groups are included Group 1: 60 patients with axial SpA Group 2 : 30 patients with SpA and peripheral joint involvement, with a medical decision to treat peripheral joint inflammation by arthrocentesis
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Patients with axial spondyloarthritis participating in the study
Arm Type
Experimental
Arm Description
People with axial spondylarthritis (60 participants),
Arm Title
Patients with peripheral spondyloarthritis participating in the study
Arm Type
Experimental
Arm Description
People with peripheral spondylarthritis (30 participants).
Intervention Type
Other
Intervention Name(s)
Blood sampling
Intervention Description
A 51 mL blood sample will be collected during the study
Intervention Type
Other
Intervention Name(s)
synovial aspiration
Intervention Description
If synovial aspiration is required in standard care for patients with peripheral spondylarthritis. Medical waste product will be collected for the study
Primary Outcome Measure Information:
Title
Profiling of open chromatin regions
Description
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
Time Frame
4 years
Title
Profiling of transcriptome
Description
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
Time Frame
4 years
Title
Profiling of the genome
Description
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
Time Frame
4 years
Title
Profiling of cytokine expression
Description
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
Time Frame
4 years
Title
Single cell transcriptome analysis
Description
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;
Time Frame
4 years
Secondary Outcome Measure Information:
Title
Measure lymphocyte levels to explore the effects of anti-IL23 treatment on the immune responses of axSpA patients
Description
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, γδ 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.
Time Frame
4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lars ROGGE, Dr
Phone
+33140613822
Email
lars.rogge@pasteur.fr
Facility Information:
Facility Name
Lars ROGGE
City
Paris
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lars Rogge, Dr
Phone
+33 1 4061 3822
Email
lars.rogge@pasteur.fr
First Name & Middle Initial & Last Name & Degree
Corinne MICELI-RICHARD, Pr
First Name & Middle Initial & Last Name & Degree
Francis BERENBAUM, Pr
First Name & Middle Initial & Last Name & Degree
Jérémie SELLAM, Dr

12. IPD Sharing Statement

Learn more about this trial

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

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