Study of the C5a/C5aR1 Axis in IgG4-associated Disease: a Potential Therapeutic Target (C5-MAG4)

Pilot Study of the C5a/C5aR1 Axis in IgG4-associated Disease: a Potential Therapeutic Target. C5-MAG4 Study.

This is a monocentric, comparative, cross-sectional, case-control study seeking to identify abnormalities of the C5a-C5aR1 axis between a population of patients with active IgG4-associated disease (MAG4) and two control groups: healthy subjects without MAG4 and patients with MAG4 in remission.

Study Overview

• Status: Not yet recruiting
• Conditions: Immunoglobulin G4-Related Disease
• Intervention / Treatment: Procedure: Blood sampling

Detailed Description

IgG4-associated disease is a rare fibrosing and inflammatory disorder whose pathophysiology remains poorly understood. Activation of certain monocyte/macrophage populations (in particular M2-type macrophages) has been shown to be involved during the course of the disease. The mechanisms behind this monocyte/macrophage activation are not known. Expression of the C5aR receptor on the surface of these populations, and preliminary findings of elevated C5a in these patients, suggest a potential role for this C5a-C5aR axis. Demonstration of the involvement of this pathway would open a path to therapeutic perspetives (C5aR inhibitors) for these patients, who frequently suffer from cortico-dependence and relapses. The aim of this research is to use healthcare technologies to identify cellular and molecular therapeutic targets in the context of the IgG4-associated disease

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria for patients suffering from IG4-related disease and patients in remission :

• age > 18
• diagnosis of IgG4-associated disease according to ACR/EULAR 2019 classification criteria (4,5) with a score ≥20.
• disease activity score (IgG4-RD Responder Index) ≥2 in at least one affected organ

Exclusion Criteria for patients suffering from IG4-related disease and patients in remission :

• presence of a differential diagnosis ("IgG4-RD mimicker") or exclusion criterion according to ACR/EULAR 2019 classification criteria (4,5).
• systemic corticosteroid treatment ≥5 mg/day ongoing or < 1 month ; Study C5-MAG4_RCAPHM21_0433 Protocol Version 1.1 of 16/01/2024 Page 15 of 41
• immunosuppressive therapy ongoing or < 3 months ;
• current biotherapy treatment or < 6 months;
• absence of signed informed consent;
• absence of affiliation to a Social Security scheme.
• patient participating in an ongoing therapeutic trial ;
• any condition which, in the opinion of the investigator, could influence the results of the study.

Inclusion criteria for healthy volunteers :

- age > 18

Exclusion criteria for healthy volunteers :

• infectious episode (temperature >38°C, flu-like signs) in the 30 days prior to inclusion;
• known inflammatory (including IG4-related disease) or autoimmune pathology;
• treatment with corticosteroids in progress or taken in the month prior to sampling, or immunosuppressants in progress or taken in the 3 months prior to sampling, or biotherapy in the 6 months prior to sampling;
• absence of signed informed consent;
• absence of affiliation to a Social Security scheme;
• persons taking part in an ongoing therapeutic trial;
• any condition which, in the opinion of the investigator, could influence the results of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: healthy volunteers	Procedure: Blood sampling; Blood sampling will be taken for further analysis
Experimental: IgG4-RD patient; Patients suffering from Immunoglobulin G4-related disease (IgG4-RD).	Procedure: Blood sampling; Blood sampling will be taken for further analysis
Experimental: patient in remission; Patients suffering from Immunoglobulin G4-related disease (IgG4-RD) but in remission.	Procedure: Blood sampling; Blood sampling will be taken for further analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum C5a concentration	The C5a concentration in the serum will be compared between of healthy volunteers and patients suffering from IG4-related disease	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
frequency of C5aR1+ monocytes among total monocytes	The frequency of C5aR1+ monocytes among total monocytes will be compared between : patients suffering from IG4-related disease and healthy volunteers; patients suffering from IG4-related disease and patients in remission	24 months
frequency of Tumor Growth Factor B+ (TGF-B+) monocytes among total monocytes	frequency of Tumor Growth Factor B+ (TGF-B+) monocytes among total monocytesill be compared between : patients suffering from IG4-related disease and healthy volunteers; patients suffering from IG4-related disease and patients in remission	24 months

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: February 14, 2024
• First Submitted That Met QC Criteria: February 14, 2024
• First Posted (Actual): February 21, 2024

Study Record Updates

• Last Update Posted (Actual): June 26, 2024
• Last Update Submitted That Met QC Criteria: June 25, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Immunoglobulin G4-Related Disease
• Other Study ID Numbers: RCAPHM21_0433

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No