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

NCT05417269 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: IMCY-MS-0012021-004974-67
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Multiple Sclerosis, Relapsing-Remitting

Keywords

RR-MS; Relapsing-Remitting Multiple Sclerosis; Multiple Sclerosis; Synthetic peptide

Outcome Measures

Primary Outcomes (5)

• Ph I Primary safety endpoint (1) - Solicited injection site and systemic AEs

  Occurrence, intensity and relationship of any solicited injection site and systemic adverse events (AEs) during a 7-day follow-up period (i.e., day of study product administration and 6 subsequent days) after each IMCY-0141 administration analysing local injection site and systemic adverse events, clinical and laboratory data.

  Up to 36 weeks

• Ph I Primary safety endpoint (2) - Unsolicited injection site and systemic AEs

  Occurrence, intensity and relationship of any unsolicited injection site (local) and systemic AEs occurring throughout the study period.

  Up to 36 weeks

• Ph I Primary safety endpoint (3) - All SAEs

  Occurrence and relationship of all serious adverse events (SAEs) occurring throughout the study period.

  Up to 36 weeks

• Ph I Primary safety endpoint (4) - Abnormalities on different parameters

  Occurrence and relationship of any abnormality in physical examination, vital signs, 12-lead ECG, MRI, haematological and biochemical laboratory parameters.

  Up to 36 weeks

• Ph II Primary efficacy endpoint - Number of CUAL

  Total cumulative number of CUAL observed on brain MRI scans (centralized reading) from week 12 till week 36 vs placebo.

  Week 12 to Week 36

Secondary Outcomes (8)

• Ph I/II Secondary endpoint (1) - Relapse rate

  At Week 36

• Ph I/II Secondary endpoint (2) - Relapse-free rate

  At Week 36

• Ph I/II Secondary endpoint (3) - EDSS Score

  At Week 36

• Ph I/II Secondary endpoint (4) - Neurofilament light chains levels

  Up to 36 weeks

• Ph II Secondary endpoint (1) - Solicited injection site and systemic AEs

  Up to 36 weeks

Other Outcomes (4)

• To assess the disease activity and the efficacy of IMCY-0141 on MRI parameters and if any IMCY-0141 dose(s) offer superior efficacy.

  Up to 36 weeks

• To assess the disease activity

  Up to 36 weeks

• To evaluate and characterize the MOG-specific CD4+ T cells induced by IMCY-0141 and its impact on autoreactive T-cell responses specific for myelin proteins.

  Up to 36 weeks

Study Arms (8)

Cohort 1 - Phase I (IMCY-0141 Dose 1)

EXPERIMENTAL

The first dose (Cohort 1) will consist of the administration of 150 μg of peptide (IMCY-0141) in two separate injections of 75 μg each (500μl each).

Drug: IMCY-0141

Cohort 2 - Phase I (IMCY-0141 Dose 2)

EXPERIMENTAL

The second dose (Cohort 2) will consist of the administration of 450 μg of peptide (IMCY-0141) in two separate injections of 225 μg each (500μl each).

Drug: IMCY-0141

Cohort 3 - Phase I (IMCY-0141 Dose 3)

EXPERIMENTAL

The third dose (Cohort 3) will consist of the administration of 1350 μg of peptide (IMCY-0141) in two separate injections of 675 μg each (500μL each).

Drug: IMCY-0141

Group 1 - Phase II (IMCY-0141 Dose 1)

EXPERIMENTAL

Administration of IMCY-0141, 150 μg combined with alum adjuvant.

Drug: IMCY-0141

Group 2 - Phase II (IMCY-0141 Dose 2)

EXPERIMENTAL

Administration of IMCY-0141, 450 μg combined with alum adjuvant.

Drug: IMCY-0141

Group 3 - Phase II (IMCY-0141 Dose 3)

EXPERIMENTAL

Administration of IMCY-0141, 1350 μg combined with alum adjuvant.

Drug: IMCY-0141

Group 4 (Placebo Group) - Phase II

PLACEBO COMPARATOR

Administration of placebo combined with alum adjuvant.

Drug: Placebo

Group 5 (Active Control Group) - Phase II

ACTIVE COMPARATOR

Parallel, Open-Label, Active Control Group Oral administration of Dimethyl Fumarate (DMF) given according to its SmPC for the whole duration of the study.

Drug: Dimethyl Fumarate

Interventions

IMCY-0141 DRUG

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.

Also known as: Imotope

Cohort 1 - Phase I (IMCY-0141 Dose 1); Cohort 2 - Phase I (IMCY-0141 Dose 2); Cohort 3 - Phase I (IMCY-0141 Dose 3); Group 1 - Phase II (IMCY-0141 Dose 1); Group 2 - Phase II (IMCY-0141 Dose 2); Group 3 - Phase II (IMCY-0141 Dose 3)

Placebo DRUG

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.

Group 4 (Placebo Group) - Phase II

Dimethyl Fumarate DRUG

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.

Also known as: DMF

Group 5 (Active Control Group) - Phase II

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female between 18 and and 45 years old.
• RR-MS according to the 2017 revisions of the McDonald Criteria.
• Patients should be newly diagnosed or have a disease duration ≤ 3 years.
• If not newly diagnosed, patients should have at least one documented clinical relapse in the last 12 months.
• Patients should present with at least 1 Gadolinium-enhancing (Gd+) T1-weighted lesion OR at least 2 new or enlarging T2-weighted lesions at screening MRI compared to a reference scan in the last 6 months.

You may not qualify if:

• EDSS ≤ 5.0 at screening.
• Women of childbearing potential (1) should use an highly effective contraception method (2) from screening and for the whole duration of the study. (1) Of child-bearing potential is defined as being post onset of menarche and not meeting any of the following conditions:
• Menopausal for at least 2 years (follicle-stimulating hormone within menopausal range),
• Having undergone bilateral tubal ligation at least 1 year previously
• Having undergone bilateral oophorectomy or hysterectomy. (2) HIGHLY EFFECTIVE contraceptive measures acceptable for the whole duration of the study have been defined based on the CTFGs recommendations on contraception and are the following:
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal),
• Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable).
• Intrauterine device (IUD)
• intrauterine hormone-releasing system (IUS)
• Monogamous relationship with vasectomized partner. Partner must have been vasectomized for at least 6 months prior to the patient's entry into the study
• Abstinence or absence of sexual relations with men.
• Ability to understand and comply with research requirements and procedures, in opinion of investigator (Signed Informed Consent)
• Secondary or primary progressive multiple sclerosis and late onset multiple sclerosis (LOMS).
• Findings on brain MRI scan indicating any clinically significant brain abnormality like:
• Doubts about MS diagnosis (based on clinically or imaging abnormalities)

Sponsors & Collaborators

• Imcyse SA: lead

Study Sites (1)

Republican Clinical Hospital, ARENSIA Exploratory Medicine

Chisinau, MD-2025, Moldova

Location

Related Publications (31)

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MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis

Interventions

Dimethyl Fumarate

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Fumarates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Vitalie LISNIC, Prof.

  ARENSIA Exploratory Medicine, Moldova

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a two-step study 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 doses offer superior efficacy relative to placebo.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study will be conducted under a Bayesian adaptive design approach comprising of two phases: * Phase I where 3 IMCY-0141 doses will be administered following a dose escalation approach. An IDMC safety assessment will allow the escalation from lower to upper dose. * Phase IIa leading to a preliminary estimate of the efficacy of each dose and determination of promising doses. The 2 doses that emerge as most promising will be recommended to advance to Phase IIb, where final efficacy will be judged, again relative to placebo. The least promising dose may be dropped, at the discretion of the trial's IDMC. All told, Phase II will enrol patients who will be randomized to IMCY-0141 or placebo or DMF. At the conclusion of Phase IIb, determined doses will be labelled effective.

Study Record Dates

• First Submitted: June 1, 2022
• First Posted: June 14, 2022
• Study Start: April 12, 2022
• Primary Completion: May 23, 2025
• Study Completion: December 31, 2025
• Last Updated: March 8, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

MO (1)