In Vitro Study of the Biological and Immunological Activity of Imotopes® Candidates on Blood Cells of Patients With Stabilized NMO

IMCY-NMO-000 In Vitro Study of the Biological and Immunological Activity of Imotopes® Candidates on Blood Cells of Patients With Stabilized Neuromyelitis Optica (PHASE 0)

This is a fundamental, prospective, multi-centres, interventional non-comparative study without the administration of a study product to patients.

A phase 0 study is particularly well adapted to early exploration of potential targeted treatments - i.e. treatments whose efficacy can only be hoped for in patients presenting specific biological characteristics in addition to being diagnosed with the targeted disease, Neuromyelitis Optica Spectrum Disorders (NMOSD) in this study. The main goal of the study will be to support the selection of Imotopes® (i.e. synthetic peptides encompassing HLA Class II T epitopes flanked by a thioreductase motif), and (i) capable of binding with class II HLA antigens of each patient and (ii) causing ex vivo the appearance of epitope -specific cytolytic CD4+ T cells.

Study Overview

• Status: Active, not recruiting
• Conditions: Neuromyelitis Optica
• Intervention / Treatment: Procedure: Blood sampling

Detailed Description

This is a fundamental, prospective, multi-centres, interventional non-comparative study without the administration of a study product to patients.

The objective is to test in vitro the binding of different Imotopes® to class II HLA antigens on peripheral blood mononuclear cell (PBMC) isolated from patients presenting a diagnosed and stabilized neuromyelitis optica spectrum disorders, as well as their ability to generate a cytolytic response directed against the immune cells involved in the maintenance and triggering of the disease (i.e. non-cytolytic T cells recognising the same epitopes and antigen presenting cells (APC) presenting the same epitopes).

The patients will be asked to provide at least 2 peripheral blood samples of approximately 100 milliliters each time, with a minimum of 14 days interval between these 2 samples. These blood samples will be taken by a member of the healthcare staff qualified to perform this type of procedure. If the results obtained with the 2 initial samples would be of interest to the Sponsor, the patient will be asked to come back for additional samplings with a maximum of 6 additional blood draws. The total volume of blood that will be taken over a 6 months period cannot exceed 500 milliliters with a maximum of 200 milliliters over a 30-day period for patients with a weight of min 50kg. The study has no other constraint.

The list of analysis planned to be performed on blood samples are presented below:

• Identification of the class II HLA antigens of each patient
• Study of the binding to HLA antigens of synthetic peptides
• Identification of peptides which, after binding to the HLA antigens, might induce a cytolytic response directed against the immune cells involved in the maintenance and triggering of the disease (i.e. non-cytolytic T cells recognising the same epitopes and APC presenting the same epitopes)
• Non selective genomic analysis (SNPs) in the scope of the single cell transcriptomic analysis technics

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bron, France, 69500
    • Hopital Pierre Wertheimer
  • Strasbourg, France, 67200
    • Hopital de Hautepierre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men or women, 18 to 65 years of age
• Patients with a confirmed diagnosis of Neuromyelitis Optica spectrum disorders according to IPND criteria (2015) and presenting a stabilized disease (no relapse) for at least 6 months.
• Patient positive for antibodies to human aquaporin 4
• Patients having granted their written informed consent to take part in this study

Exclusion Criteria:

• Ongoing pregnancy
• Ongoing treatment with immunosuppressive agents other than those listed below under section "authorized background therapy"
• Any investigational product in the last 3 months or less than 5 times the estimated half-life of the investigational product whichever is the longer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Test of Imotopes® candidates on blood cells of patients with stabilized NMO; To test in vitro the binding of different Imotopes® to class II HLA antigens on PBMC isolated from patients presenting a diagnosed and stabilized neuromyelitis optica spectrum disorders, as well as their ability to generate a cytolytic response directed against the immune cells involved in the maintenance and triggering of the disease (i.e. non-cytolytic T cells recognising the same epitopes and antigen presenting cells (APC) presenting the same epitopes).

Procedure: Blood sampling; The patients will be asked to provide at least 2 peripheral blood samples of approximately 100 milliliters each time, with a minimum of 14 days interval between these 2 samples.If the results obtained with the 2 initial samples would be of interest to the Sponsor, the patient will be asked to come back for additional samplings with a maximum of 6 additional blood draws

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure in vitro binding of Imotopes®	Characterize, in vitro, the binding of different Imotopes® to class II HLA antigens on PBMC isolated from patients with NMO	Through study completion, an average of 1 year
Measure Cytolytic response against Antigen-Presenting Cells (APC)	Measure the ability of Imotopes® to generate a cytolytic response directed against the immune cells involved in the maintenance and triggering of the disease (i.e. non-cytolytic T cells recognising the same epitopes and APC presenting the same epitopes)	Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Imcyse SA
• Investigators: Principal Investigator: Jerome De Seze, MD, Hôpital de Hautepierre, Strasbourg

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2020
• Primary Completion (Estimated): February 28, 2025
• Study Completion (Estimated): February 28, 2025

Study Registration Dates

• First Submitted: October 29, 2020
• First Submitted That Met QC Criteria: November 9, 2020
• First Posted (Actual): November 16, 2020

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Eye Diseases; Optic Nerve Diseases; Cranial Nerve Diseases; Myelitis, Transverse; Optic Neuritis; Neuromyelitis Optica
• Other Study ID Numbers: IMCY-NMO-000

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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