Multiple Sclerosis, Relapsing-RemittingPhase 1/2NCT05417269

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

A Phase 1/2 study testing IMCY-0141 and Dimethyl Fumarate in people with Multiple Sclerosis, Relapsing-Remitting, run by Imcyse SA at 1 site in Moldova.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 to 45 years
Conditions the study is for: Multiple Sclerosis, Relapsing-Remitting
What is being tested?: IMCY-0141 and Dimethyl Fumarate
Type of treatment: Vaccines, Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 150 participants
Where: 1 siteMoldova
Study dates: 12 Apr 2022to 31 Dec 2025
Phase: Phase 1/2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 45 years
All sexes
No healthy volunteers
Adult

Who may be able to join

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.
No background MS treatment at the time of study treatment start (refer to exclusion criteria for details about authorized washout period for some first line treatment).

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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)

Who cannot join

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)
PML cases (positive PML checklist according to "suspected PML case adjudication instructions")
Co-morbidities influencing the MS disease evolution (i.e. Tumor, large infarction, CSF obstruction)
Patient has complete transverse myelitis or bilateral optic neuritis.

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Systemic corticosteroids or adrenocorticotropic hormone (ACTH) without chronic use within 30 days prior to screening MRI.
Treatment with rituximab, ocrelizumab, mitoxantrone, or lymphocyte depleting therapies (e.g., alemtuzumab, anti-CD4, cladribine, cyclophosphamide, total body irradiation, bone marrow transplantation) within 48 weeks prior to study treatment start.
Use of lymphocyte trafficking blockers (e.g., natalizumab, fingolimod) within 24 weeks prior to study treatment start.
Treatment with β-interferons or glatiramer acetate within 4 weeks prior to study treatment start.
Treatment with teriflunomide within 12 weeks prior to study treatment start.
Exposure to dimethyl fumarate within 6 months prior to study treatment start.
Any investigational drug within the past 6 months at the time of study treatment start.
Immunosuppressive therapy including chronic use of systemic steroids in past year. Topical, inhalational or intranasal corticosteroids are allowed.
Primary or secondary immune deficiency disorders with the exception of well-controlled diabetes or thyroid disorder.
Patients with combined other auto-immune or inflammatory disorders.
Have signs or symptoms of active or long COVID infection or a positive COVID PCR test during the screening period. In the case of PCR positivity, a reswabbing will be done. If reswabbing returns a negative result, the initiation of study treatment can occur.
Have evidence of current or past human immunodeficiency virus (HIV-1 and 2), Hepatitis B or Hepatitis C infection: HBsAg+ or anti-HBc+; anti-HCV+ (unless the polymerase chain reaction [PCR] for HBV DNA (hepatitis B) or HCV RNA (hepatitis C) is negative according to local procedure).
Current signs or symptoms of infection at time of study treatment start or within 2 weeks prior to planned administration of the study product or intravenous antibiotics within 2 months prior to the first planned administration of the study product.
Live, attenuated vaccine within 3 months prior to the first planned administration of the study product.
Inability to comply with MRI scanning, including contraindications to MRI such as known allergy to gadolinium contrast media, claustrophobia, presence of a pacemaker, cochlear implants, ferromagnetic devices or clips, intracranial vascular clips, insulin pumps, nerve stimulators.
Any other significant disease, disorder or finding which may significantly increase the risk to the patient because of participation in the study, affect the ability of the patient to participate in the study or impair interpretation of the study data.
Patients with a known hypersensitivity to any component of the drug product.
Patients with psychiatric or cognitive disorders.
History of MS related seizures not adequately controlled by medications.
History of cancer, except adequately treated basal cell or squamous cell carcinoma of the skin (no more than 3 lesions requiring treatment in lifetime) or carcinoma in situ/cervical intraepithelial neoplasia of the uterine cervix, unless considered cured > 5 years
Abnormal renal function defined by creatinine clearance ≤ 60 ml/min/1.73m2.
Patient with total lymphocytes count < 1000/mm3.
Patient with abnormal hepatic function defined as any liver enzyme > 3 ULN, bilirubin > 3 ULN with exception of Gilbert Syndrome.
Breastfeeding/lactating or pregnant women.
1. Patient HLA DRB103:01 positive
1. Patients already included in Phase I

Trial locations and contacts

1 site in 1 country.

Moldova1 site

Republican Clinical Hospital, ARENSIA Exploratory Medicine
Chisinau, MD-2025

Other trials in Moldova

About this study

Official title: 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)

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.

Read the 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
Being tested: IMCY-0141, Placebo, Dimethyl Fumarate
Keywords: RR-MS, Relapsing-Remitting Multiple Sclerosis, Multiple Sclerosis, Synthetic peptide
Medical subject headings: Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

IMCY-0141Drug
Also called Imotope
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.
PlaceboDrug
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.
Dimethyl FumarateDrug
Also called DMF
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.

Study groups in NCT05417269
Study group	Role	What they receive
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). Receives: 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). Receives: 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). Receives: Drug: IMCY-0141
Group 1 - Phase II (IMCY-0141 Dose 1)	Experimental	Administration of IMCY-0141, 150 μg combined with alum adjuvant. Receives: Drug: IMCY-0141
Group 2 - Phase II (IMCY-0141 Dose 2)	Experimental	Administration of IMCY-0141, 450 μg combined with alum adjuvant. Receives: Drug: IMCY-0141
Group 3 - Phase II (IMCY-0141 Dose 3)	Experimental	Administration of IMCY-0141, 1350 μg combined with alum adjuvant. Receives: Drug: IMCY-0141
Group 4 (Placebo Group) - Phase II	Placebo comparator	Administration of placebo combined with alum adjuvant. Receives: 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. Receives: Drug: Dimethyl Fumarate

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Week 12 to Week 36

Secondary outcomes (8)

Ph I/II Secondary endpoint (1) - Relapse rate
Annualized relapse rate at week 36 vs baseline
Measured: At Week 36
Ph I/II Secondary endpoint (2) - Relapse-free rate
Proportion of relapse-free patients at week 36 vs baseline
Measured: At Week 36
Ph I/II Secondary endpoint (3) - EDSS Score
EDSS score at week 36 vs screening
Measured: At Week 36
Ph I/II Secondary endpoint (4) - Neurofilament light chains levels
Neurofilament light chains levels in the serum of the patient (sNfL) at baseline, weeks 2, 4, 6, 8, 10, 12, 24 and 36.
Measured: Up to 36 weeks
Ph II Secondary endpoint (1) - Solicited injection site and systemic AEs
Occurrence, intensity and relationship of any solicited local and systemic adverse event (AE) during a 7-day follow-up period (i.e., day of study drug administration and 6 subsequent days) after each IMCY-0141 administration.
Measured: Up to 36 weeks
Ph II Secondary 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.
Measured: Up to 36 weeks
Ph II Secondary endpoint (3) - All SAEs
Occurrence and relationship of all serious adverse events (SAEs) occurring throughout the study period.
Measured: Up to 36 weeks
Ph II Secondary endpoint (4) - Abnormalities on different parameters
Occurrence, intensity and relationship of any abnormality in physical examination, vital signs, 12-lead ECG, MRI, haematological and biochemical laboratory parameters.
Measured: Up to 36 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

12 Apr 202231 Dec 2025

First posted14 Jun 2022
Study start12 Apr 2022
Primary completion23 May 2025 (estimated)
Study completion31 Dec 2025 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (31)Papers the sponsor has linked to this study.
Other trials for Multiple Sclerosis, Relapsing-RemittingStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Model description: 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.
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 150 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05417269
Sponsor's protocol ID: IMCY-MS-001
Other IDs: 2021-004974-67
Status last verified: Mar 2024
First submitted: 1 Jun 2022
Last updated: 8 Mar 2024
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Malek Abrahimians E, Carlier VA, Vander Elst L, Saint-Remy JM. MHC Class II-Restricted Epitopes Containing an Oxidoreductase Activity Prompt CD4(+) T Cells with Apoptosis-Inducing Properties. Front Immunol. 2015 Sep 2;6:449. doi: 10.3389/fimmu.2015.00449. eCollection 2015.
PubMed 26388872
Carlin BP, Louis TA. Bayesian Methods for Data Analysis, 3rd ed. 2009; Boca Raton, FL: CRC Press.
Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Fisher E, Brinar VV, Giovannoni G, Stojanovic M, Ertik BI, Lake SL, Margolin DH, Panzara MA, Compston DA; CARE-MS I investigators. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012 Nov 24;380(9856):1819-28. doi: 10.1016/S0140-6736(12)61769-3. Epub 2012 Nov 1.
PubMed 23122652
Coles AJ, Twyman CL, Arnold DL, Cohen JA, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Miller T, Fisher E, Sandbrink R, Lake SL, Margolin DH, Oyuela P, Panzara MA, Compston DA; CARE-MS II investigators. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet. 2012 Nov 24;380(9856):1829-39. doi: 10.1016/S0140-6736(12)61768-1. Epub 2012 Nov 1.
PubMed 23122650
Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency. Guideline on the clinical investigation of medicinal products for the treatment of multiple sclerosis. CHMP/771815/2011 Rev. 2. Effective date 1 October 2015.
Compston A, Coles A. Multiple sclerosis. Lancet. 2008 Oct 25;372(9648):1502-17. doi: 10.1016/S0140-6736(08)61620-7.
PubMed 18970977
Friese MA, Fugger L. Autoreactive CD8+ T cells in multiple sclerosis: a new target for therapy? Brain. 2005 Aug;128(Pt 8):1747-63. doi: 10.1093/brain/awh578. Epub 2005 Jun 23.
PubMed 15975943
Goldenberg MM. Multiple sclerosis review. P T. 2012 Mar;37(3):175-84. No abstract available.
PubMed 22605909
Guo X, Carlin BP. Separate and joint modeling of longitudinal and event time data using standard computer packages. The American Statistician; 2004; 58, 16-24.
Johnson KP, Brooks BR, Cohen JA, Ford CC, Goldstein J, Lisak RP, Myers LW, Panitch HS, Rose JW, Schiffer RB. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group. Neurology. 1995 Jul;45(7):1268-76. doi: 10.1212/wnl.45.7.1268.
PubMed 7617181
Kampman MT, Brustad M. Vitamin D: a candidate for the environmental effect in multiple sclerosis - observations from Norway. Neuroepidemiology. 2008;30(3):140-6. doi: 10.1159/000122330. Epub 2008 Apr 2.
PubMed 18382112
Kappos L, Antel J, Comi G, Montalban X, O'Connor P, Polman CH, Haas T, Korn AA, Karlsson G, Radue EW; FTY720 D2201 Study Group. Oral fingolimod (FTY720) for relapsing multiple sclerosis. N Engl J Med. 2006 Sep 14;355(11):1124-40. doi: 10.1056/NEJMoa052643.
PubMed 16971719
Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983 Nov;33(11):1444-52. doi: 10.1212/wnl.33.11.1444.
PubMed 6685237
McCarthy DP, Richards MH, Miller SD. Mouse models of multiple sclerosis: experimental autoimmune encephalomyelitis and Theiler's virus-induced demyelinating disease. Methods Mol Biol. 2012;900:381-401. doi: 10.1007/978-1-60761-720-4_19.
PubMed 22933080
McKay KA, Kwan V, Duggan T, Tremlett H. Risk factors associated with the onset of relapsing-remitting and primary progressive multiple sclerosis: a systematic review. Biomed Res Int. 2015;2015:817238. doi: 10.1155/2015/817238. Epub 2015 Jan 31.
PubMed 25802867

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 8 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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)
ClinicalTrials.gov ID: NCT05417269
Acronym / sponsor ID: IMCY-MS-001
Conditions: Multiple Sclerosis, Relapsing-Remitting
Keywords: RR-MS, Relapsing-Remitting Multiple Sclerosis, Multiple Sclerosis, Synthetic peptide
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Unknown status
Enrolment: 150 participants (estimated)
Lead sponsor: Imcyse SAIndustry (pharma, biotech, devices)
Study start: 12 Apr 2022 (actual)
Primary completion: 23 May 2025 (estimated)
Study completion: 31 Dec 2025 (estimated)
First posted: 14 Jun 2022 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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).

Detailed description

The Sample Size determined for this study is as follows:

Phase I:

Phase II:

Placebo
IMCY-0141 dose 1
IMCY-0141 dose 2
IMCY-0141 dose 3
DMF (open label)

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 8
Model description: 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.

Arm	Type	Receives
Cohort 1 - Phase I (IMCY-0141 Dose 1)	Experimental	Drug: IMCY-0141The 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).
Cohort 2 - Phase I (IMCY-0141 Dose 2)	Experimental	Drug: IMCY-0141The 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).
Cohort 3 - Phase I (IMCY-0141 Dose 3)	Experimental	Drug: IMCY-0141The 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).
Group 1 - Phase II (IMCY-0141 Dose 1)	Experimental	Drug: IMCY-0141Administration of IMCY-0141, 150 μg combined with alum adjuvant.
Group 2 - Phase II (IMCY-0141 Dose 2)	Experimental	Drug: IMCY-0141Administration of IMCY-0141, 450 μg combined with alum adjuvant.
Group 3 - Phase II (IMCY-0141 Dose 3)	Experimental	Drug: IMCY-0141Administration of IMCY-0141, 1350 μg combined with alum adjuvant.
Group 4 (Placebo Group) - Phase II	Placebo comparator	Drug: PlaceboAdministration of placebo combined with alum adjuvant.
Group 5 (Active Control Group) - Phase II	Active comparator	Drug: Dimethyl FumarateParallel, Open-Label, Active Control Group Oral administration of Dimethyl Fumarate (DMF) given according to its SmPC for the whole duration of the study.

Who may qualify

Ages: 18 to 45 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (18 listed)

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.

Key exclusion criteria (32 listed)

Secondary or primary progressive multiple sclerosis and late onset multiple sclerosis (LOMS).
Findings on brain MRI scan indicating any clinically significant brain abnormality like:
Patient has complete transverse myelitis or bilateral optic neuritis.
Systemic corticosteroids or adrenocorticotropic hormone (ACTH) without chronic use within 30 days prior to screening MRI.
Treatment with rituximab, ocrelizumab, mitoxantrone, or lymphocyte depleting therapies (e.g., alemtuzumab, anti-CD4, cladribine, cyclophosphamide, total body irradiation, bone marrow transplantation) within 48 weeks prior to study treatment start.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
IMCY-0141Also: ImotopeThe 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	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)
PlaceboThe 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	Group 4 (Placebo Group) - Phase II
Dimethyl FumarateAlso: DMFDimethyl 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.	Drug	Group 5 (Active Control Group) - Phase II

Primary outcome

Ph I Primary safety endpoint (1) - Solicited injection site and systemic AEs
Time frame: Up to 36 weeks
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.
Ph I Primary safety endpoint (2) - Unsolicited injection site and systemic AEs
Time frame: Up to 36 weeks
Occurrence, intensity and relationship of any unsolicited injection site (local) and systemic AEs occurring throughout the study period.
Ph I Primary safety endpoint (3) - All SAEs
Time frame: Up to 36 weeks
Occurrence and relationship of all serious adverse events (SAEs) occurring throughout the study period.
Ph I Primary safety endpoint (4) - Abnormalities on different parameters
Time frame: Up to 36 weeks
Occurrence and relationship of any abnormality in physical examination, vital signs, 12-lead ECG, MRI, haematological and biochemical laboratory parameters.
Ph II Primary efficacy endpoint - Number of CUAL
Time frame: Week 12 to Week 36
Total cumulative number of CUAL observed on brain MRI scans (centralized reading) from week 12 till week 36 vs placebo.

8 secondary outcomes

Ph I/II Secondary endpoint (1) - Relapse rate
Time frame: At Week 36
Ph I/II Secondary endpoint (2) - Relapse-free rate
Time frame: At Week 36
Ph I/II Secondary endpoint (3) - EDSS Score
Time frame: At Week 36
Ph I/II Secondary endpoint (4) - Neurofilament light chains levels
Time frame: Up to 36 weeks
Ph II Secondary endpoint (1) - Solicited injection site and systemic AEs
Time frame: Up to 36 weeks
Ph II Secondary endpoint (2) - Unsolicited injection site and systemic AEs
Time frame: Up to 36 weeks
Ph II Secondary endpoint (3) - All SAEs
Time frame: Up to 36 weeks
Ph II Secondary endpoint (4) - Abnormalities on different parameters
Time frame: Up to 36 weeks

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2024.
Background: PubMed 26388872Malek Abrahimians E, Carlier VA, Vander Elst L, Saint-Remy JM. MHC Class II-Restricted Epitopes Containing an Oxidoreductase Activity Prompt CD4(+) T Cells with Apoptosis-Inducing Properties. Front Immunol. 2015 Sep 2;6:449. doi: 10.3389/fimmu.2015.00449. eCollection 2015.
BackgroundCarlin BP, Louis TA. Bayesian Methods for Data Analysis, 3rd ed. 2009; Boca Raton, FL: CRC Press.
Background: PubMed 23122652Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Fisher E, Brinar VV, Giovannoni G, Stojanovic M, Ertik BI, Lake SL, Margolin DH, Panzara MA, Compston DA; CARE-MS I investigators. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012 Nov 24;380(9856):1819-28. doi: 10.1016/S0140-6736(12)61769-3. Epub 2012 Nov 1.
Background: PubMed 23122650Coles AJ, Twyman CL, Arnold DL, Cohen JA, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Miller T, Fisher E, Sandbrink R, Lake SL, Margolin DH, Oyuela P, Panzara MA, Compston DA; CARE-MS II investigators. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet. 2012 Nov 24;380(9856):1829-39. doi: 10.1016/S0140-6736(12)61768-1. Epub 2012 Nov 1.
BackgroundCommittee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency. Guideline on the clinical investigation of medicinal products for the treatment of multiple sclerosis. CHMP/771815/2011 Rev. 2. Effective date 1 October 2015.
Background: PubMed 18970977Compston A, Coles A. Multiple sclerosis. Lancet. 2008 Oct 25;372(9648):1502-17. doi: 10.1016/S0140-6736(08)61620-7.
Background: PubMed 15975943Friese MA, Fugger L. Autoreactive CD8+ T cells in multiple sclerosis: a new target for therapy? Brain. 2005 Aug;128(Pt 8):1747-63. doi: 10.1093/brain/awh578. Epub 2005 Jun 23.
Background: PubMed 22605909Goldenberg MM. Multiple sclerosis review. P T. 2012 Mar;37(3):175-84. No abstract available.
BackgroundGuo X, Carlin BP. Separate and joint modeling of longitudinal and event time data using standard computer packages. The American Statistician; 2004; 58, 16-24.
Background: PubMed 7617181Johnson KP, Brooks BR, Cohen JA, Ford CC, Goldstein J, Lisak RP, Myers LW, Panitch HS, Rose JW, Schiffer RB. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group. Neurology. 1995 Jul;45(7):1268-76. doi: 10.1212/wnl.45.7.1268.
Background: PubMed 18382112Kampman MT, Brustad M. Vitamin D: a candidate for the environmental effect in multiple sclerosis - observations from Norway. Neuroepidemiology. 2008;30(3):140-6. doi: 10.1159/000122330. Epub 2008 Apr 2.
Background: PubMed 16971719Kappos L, Antel J, Comi G, Montalban X, O'Connor P, Polman CH, Haas T, Korn AA, Karlsson G, Radue EW; FTY720 D2201 Study Group. Oral fingolimod (FTY720) for relapsing multiple sclerosis. N Engl J Med. 2006 Sep 14;355(11):1124-40. doi: 10.1056/NEJMoa052643.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Vitalie LISNIC, Prof. principal investigator

ARENSIA Exploratory Medicine, Moldova

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing IMCY-0141 and Dimethyl Fumarate in people with Multiple Sclerosis, Relapsing-Remitting, run by Imcyse SA at 1 site in Moldova.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 8 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Moldova. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Ph I Primary safety endpoint (1) - Solicited injection site and systemic AEs (time frame: Up to 36 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05417269, which also lists 31 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2024.