Exploration of the Cellular and Molecular Mechanisms in Patients Receiving Biotherapies Targeting the IL-23/IL-17 Axis in Cutaneous Psoriasis

Psoriasis Clinical Trial

— Pso23  

Official title:

Exploration of the Cellular and Molecular Mechanisms in Patients Receiving Biotherapies Targeting the IL-23/IL-17 Axis in Cutaneous Psoriasis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05111210
• Other study ID #: 2020-076
• Status: Recruiting
• Start date: December 14, 2021
• Est. completion date: December 2024

Study information

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

Clinical Trial Summary

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

Description:

The aim of this project is to study the cellular and molecular mechanisms in patients receiving anti-IL-23 biologics as treatment for cutaneous psoriasis, in order to improve the understanding of the role of IL-23/IL-17 axis in this pathology.

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 in patients with skin psoriasis and correlate it with the patient's genotype

• Identify at the single cell level the cells expressing IL-23R and/or producing IL-17 in the skin of patients with skin psoriasis;

• Characterize the in vivo effects of anti-IL-23 therapy on the immune responses of patients with skin psoriasis, by analysing gene expression and protein secretion in whole blood cultures before and after treatment; The secondary objective of this study is to identify mechanisms of non-response to anti-IL-23 therapy in cutaneous psoriasis patients.

The study population to be included are patients affected by cutaneous psoriasis, requiring systemic biological treatment and attended to in the Dermatology Department of the Cochin Hospital. Patients will be divided into two groups: Group 1 patients will participate once before initiation of therapy, Group 2 will participate before and after initiation of anti-IL-23 biologic treatment.

Group 1: 10 patients with cutaneous psoriasis for the phenotypic and transcriptional analyses of T cell populations in peripheral blood. These patients will be sampled once before initiation of biotherapy.

• Group 2: 40 patients with a medical decision to treat cutaneous psoriasis with an anti-IL-23 biologic. These patients will be sampled twice (before and after initiation of therapy), for the analysis of blood immune cell populations using spectral flow cytometry, and immune responses using whole blood cultures. Skin biopsies will be obtained from a subset of 10 patients to analyse the skin transcriptome, before and after treatment with anti-IL-23 biologics.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

All patients:

• Adults (>18 years)

• Presenting with cutaneous psoriasis

• Patients have signed an informed consent

• Beneficiary of the health insurance, except for the AME Only for patients of Group 1

• Patients require systemic treatment for psoriasis

• Patients are naïve to biological therapies

Only for patients of Group 2:

• Patients requiring treatment with anti-IL-23 biologics (guselkumab, risankizumab, tildrakizumab) upon referent physician's decision.

• Patients are naïve to biological therapies or have received only one biologic, with a "wash-out" period of at least 4 months

Non inclusion Criteria:

For all :

• Patient is minor

• Patient is pregnant or breastfeeding

• Patient is immunocompromised

• Patient is under legal protection, curatorship, guardianship

• Patient refuses consent

• Patient is unable to comply with study requirements for geographic, social or psychiatric reason.

• Beneficiary of the AME Only for patients of Group 1

• Patient has received biologics Only for patients of Group 2

• Patient has a contraindication to the chosen biotherapy

• Patient has received biologics within the last 4 months

• Patient has been treated with 2 or more biologics

• Patient has already received an anti-IL-23 biologic

Related Conditions & MeSH terms

• Psoriasis

Intervention

Other:
• Blood sample
Blood will be collected in tubes heparinés BD (Vacutainer), homogenised, and immediately transported at room temperature to Institut Pasteur to be further processed
• Data collection
collection of socio-demographic, clinical and biological data.
• skin biopsies
skin biopsies of 4 mm in diameter. These samples will not be taken on the face or in an area of skin folds

Locations

Country	Name	City	State
France	Lars ROGGE	Paris	Ile De France

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), of the transcriptome (RNA-seq), of the genome (genotyping), and of cytokine expression (Proximity Extension Assay technology) in T lymphocytes from patients with cutaneous psoriasis, untreated or treated with IL-23 in vitro	3 years
Primary	Single cell transcriptome analysis	Single cell transcriptome analysis of skin biopsies from patients with cutaneous psoriasis, before and after anti-IL-23 therapy.	3 years
Primary	Analysis of the frequencies of MAIT, iNKT, ?d TCR+, CD4+ et CD8+ T cells	Analysis of the frequencies of MAIT, iNKT, ?d TCR+, CD4+ et CD8+ T cells in the peripheral blood of patients with cutaneous psoriasis, before and after initiation of anti-IL-23 treatment to analyse the effect of anti-IL-23 therapy on the immune responses.	3 years
Secondary	Definition of an immune response signature	immune response signature :gene expression, protein secretion or immune cell frequencies that correlates with therapeutic response to anti-IL-23 therapy in cutaneous psoriasis patients.	3 years