NCT05417269

IMCY-0141 Safety and Efficacy in Multiple Sclerosis - ISEMIS Study

A Phase I/II Dose Escalation/Adaptive Design Study to Evaluate the Safety and Efficacy of IMCY-0141 in Patients With Relapsing Remitting-Multiple Sclerosis (RR-MS)

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 150 (estimated)
• Sponsor: Imcyse SA · Industry
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Not accepted

Summary

The IMCY-MS-001 study is a study to test a new experimental drug, IMCY-0141, for the treatment of Relapsing-Remitting Multiple Sclerosis (RR-MS). The pathophysiology of MS with known myelin autoantigens and T cell epitopes makes this disease a particularly attractive indication for development of an immunotherapeutic based on the Imcyse technology. Based on the unique mechanism of action of the drug, IMCY-0141 administered as early as possible after confirmation of the diagnosis may potentially switch-off the autoimmune process and limit the corresponding myelin destruction. Newly (recently) diagnosed patients will be targeted to tackle the disease at its onset. Before launching any efficacy studies, safety of IMCY-0141 in MS patients must be evaluated with a phase I, open-label, dose escalation clinical trial to evaluate the safety of three IMCY-0141 doses followed by a phase II, double-blind, randomized study with an adaptive design to determine if any IMCY-0141 dose(s) offer superior efficacy relative to placebo and to assess immune responses and biomarker data as potential early predictors of efficacy of IMCY-0141 in adults presenting with RR-MS.

Detailed description

The Sample Size determined for this study is as follows: Phase I: A total of 12 patients (4 patients in each of 3 dose cohorts) are planned to be enrolled. The study sample size has been estimated as adequate to provide a reliable safety assessment of the tested doses. All primary, secondary and exploratory endpoints will be summarized by descriptive statistics (continuous variables) or frequency tables (categorical variables), by dose group and overall. Additional patients may be enrolled if requested by the IDMC (Independent Data Monitoring Committee). Phase II: The sample size estimation is based on the total cumulative number of CUAL observed on brain MRI scans from week 12 till week 36. The study sample size has been estimated as adequate to determine if any IMCY-0141 doses offer superior efficacy (as measured by CUAL) relative to placebo. Using the negative binomial model for CUAL, a maximum total of 150 patients are planned to be enrolled (including the 12 patients enrolled in phase I), with 30 patients randomized to each of five groups: * Placebo * IMCY-0141 dose 1 * IMCY-0141 dose 2 * IMCY-0141 dose 3 * DMF (open label) During the adaptive design phase (Phase IIa), a minimum of 40 patients will be enrolled (with 8 patients randomized to each of five groups) and analyzed along with the 12 phase I patients as detailed here: * Placebo: 8 patients * IMCY-0141 dose 1: 8 patients + 4 phase I patients * IMCY-0141 dose 2: 8 patients + 4 phase I patients * IMCY-0141 dose 3: 8 patients + 4 phase I patients * DMF (open label) : 8 patients During the Phase IIb part, up to 98 additional patients will be enrolled in order to get up to 150 patients spread over the groups selected for Phase IIb, with a maximum 30 patients randomized to DMF. These sample sizes are sufficient to deliver Type I errors less than 5% in our chosen null scenarios, and unconditional powers greater than 75% and conditional powers greater than 90% in our two alternative scenarios.

Conditions

• Multiple Sclerosis, Relapsing-Remitting

Interventions

Type	Name	Description
DRUG	IMCY-0141	The investigational medicinal product (IMP) consists in a small synthetic peptide (23 amino acids - IMCY-0141) combining a known human epitope of MOG flanked with a thioredox motif, presented in the form of a freeze-dried sterile powder and diluent for subcutaneous (SC) administration. The diluent includes the adjuvant aluminium hydroxide (alum) at a concentration of 900 μg/mL. Treatment will be injected within 4h of resuspension of the powder with the diluent. Treatment will consist of 6 immunizations (separated by 14 days) of the IMP by SC injection in the upper arm, in the region of the triceps (lateral part of the arm, midway between the elbow and the shoulder). Half of the dose to be administered will be injected concomitantly in both arms.
DRUG	Placebo	The placebo will be administered by subcutaneous route, once every two weeks for 6 times. Placebo will be administered to patients randomized in the "placebo" group during Phase II only.
DRUG	Dimethyl Fumarate	Dimethyl Fumarate (DMF) will be given orally, according to its SmPC for the whole duration of the study. Dimethyl Fumarate (DMF) will be administered to patients randomized in the active control group during Phase II only.

Timeline

• Start date: 2022-04-12
• Primary completion: 2025-05-23
• Completion: 2025-12-31
• First posted: 2022-06-14
• Last updated: 2024-03-08

Locations

1 site across 1 country: Moldova