Ignite Creation Date:
2024-05-06 @ 6:05 PM
Last Modification Date:
2024-10-26 @ 2:41 PM
Study NCT ID:
NCT05544448
Status:
UNKNOWN
Last Update Posted:
2022-09-16
First Post:
2022-09-14
Brief Title:
In Vitro Effect Study of Interleukin-2 Muteins on Regulatory T Cells of Patients With Different Autoimmune Allo-immune or Inflammatory Diseases
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
n Vitro Effect Study of Interleukin-2 Muteins on Regulatory T Cells of Patients With Different Autoimmune Allo-immune or Inflammatory Diseases
Status:
UNKNOWN
Status Verified Date:
2022-09
Last Known Status:
NOT_YET_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MuTreg
Brief Summary:
Interleukin 2 IL-2 is a critical cytokine for the survival and function of regulatory T cells LTreg This cytokine has a dual role in the immune system IL-2 stimulates immune responses by acting on the intermediate affinity IL-2R receptor IL-2Rβγ expressed by conventional T cells LTconv during activation but also contributes to the inhibition of immune responses via LTreg that express the high affinity receptor IL-2Rαβγ
This difference in IL-2 receptor affinity for IL-2 has led to the development of low-dose IL-2 therapy to stimulate LTreg and improve control of excessive inflammation in autoimmune AID inflammatory or alloimmune diseases Low-dose IL-2 therapy is being studied in several of these diseases such as systemic lupus erythematosus type 1 diabetes alopecia HCV hepatitis C virus-induced vasculitis atopic dermatitis and chronic allo-transplantation-related graft-versus-host disease GVHD
Some of these studies have shown an increase in LTreg numbers and an improvement in certain clinical signs
To improve LTreg targeting in autoimmune diseases inflammatory diseases or GVHD mutated IL-2s muteins have been developed with selective LTreg agonist properties
These IL-2 muteins are linked to an Fc fragment to increase their half-life Two IL-2 variants IL-2Vs-Fc preferentially stimulate STAT5 phosphorylation in LTregs compared to conventional FoxP3- LTconv CD4 or CD8 T cells
This difference in IL-2 receptor affinity for IL-2 has led to the development of low-dose IL-2 therapy to stimulate LTreg and improve control of excessive inflammation in autoimmune AID inflammatory or alloimmune diseases Low-dose IL-2 therapy is being studied in several of these diseases such as systemic lupus erythematosus type 1 diabetes alopecia HCV hepatitis C virus-induced vasculitis atopic dermatitis and chronic allo-transplantation-related graft-versus-host disease GVHD
Some of these studies have shown an increase in LTreg numbers and an improvement in certain clinical signs
To improve LTreg targeting in autoimmune diseases inflammatory diseases or GVHD mutated IL-2s muteins have been developed with selective LTreg agonist properties
These IL-2 muteins are linked to an Fc fragment to increase their half-life Two IL-2 variants IL-2Vs-Fc preferentially stimulate STAT5 phosphorylation in LTregs compared to conventional FoxP3- LTconv CD4 or CD8 T cells
Detailed Description:
Hypothesis
In order to confirm that this differential effect of IL-2 muteins already established in non-diseased controls is also observed in patients with autoimmune diseases inflammatory diseases or GVHD a pilot in vitro study should be conducted on a small number of patients blood samples 5 or 10 depending on the pathology
Objective
Conduct a multicentre pilot study to confirm the hypothesis that IL-2 muteins preferentially activate the STAT5 pathway in LTreg compared to LTconv in patients with GVHD acquired bone marrow aplasia systemic lupus erythematosus multiple sclerosis rheumatoid arthritis autoimmune thyroiditis vitiligo alopecia or atopic dermatitis
Method
At the inclusion patients will have a blood sample collected for in vitro research purposes Their clinical data will also be collected
Conclusion This trial should provide in vitro proof-of-principle of the efficacy of IL-2 muteins on LTreg and could eventually lead to a therapeutic trial
In order to confirm that this differential effect of IL-2 muteins already established in non-diseased controls is also observed in patients with autoimmune diseases inflammatory diseases or GVHD a pilot in vitro study should be conducted on a small number of patients blood samples 5 or 10 depending on the pathology
Objective
Conduct a multicentre pilot study to confirm the hypothesis that IL-2 muteins preferentially activate the STAT5 pathway in LTreg compared to LTconv in patients with GVHD acquired bone marrow aplasia systemic lupus erythematosus multiple sclerosis rheumatoid arthritis autoimmune thyroiditis vitiligo alopecia or atopic dermatitis
Method
At the inclusion patients will have a blood sample collected for in vitro research purposes Their clinical data will also be collected
Conclusion This trial should provide in vitro proof-of-principle of the efficacy of IL-2 muteins on LTreg and could eventually lead to a therapeutic trial
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None