A first in human trial for evaluating both safety and preliminary efficacy of a single infusion of stimulated autologous CD4+ cells in patients with Relapsing- Remitting multiple sclerosis

• Register: EUCTR
• Last refreshed on: 8 August 2016
• Main ID: EUCTR2014-001081-99-BE
• Date of registration: 03/12/2014
• Prospective Registration: Yes
• Primary sponsor: ImCyse S.A
• Public title: A first in human trial for evaluating both safety and preliminary efficacy of a single infusion of stimulated autologous CD4+ cells in patients with Relapsing- Remitting multiple sclerosis
• Scientific title: A clinical trial to document safety and radiological disease activity in patients with relapsing-remitting multiple sclerosis treated with autologous CD4+ cells, stimulated and expanded ex vivo by a myelin oligodendrocyte glycoprotein (MOG) peptide modified by the introduction of a thioreductase motif into the flanking residues of the T cell epitope (SCLEROLYM trial). First-in-human trial - SCLEROLYM Trial
• Date of first enrolment: 16/12/2014
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001081-99
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium

Contacts

• Name: Jean-Louis Poplavsky
• Affiliation: ImCyse

• Name: Jean-Louis Poplavsky
• Affiliation: ImCyse

Key inclusion & exclusion criteria

Inclusion criteria:
• Males and females 18 to 60 years of age
• Patients closely followed up by the investigators for at least one year prior to inclusion (i.e. prior to the start of the baseline phase), to ensure that all possible episodes of clinical relapses which occurred during this interval of time were recorded and documented by the investigational centre
• Multiple sclerosis that meets the 2010 revised McDonald criteria
• Relapsing/remitting type of multiple sclerosis (which includes clinically isolated syndromes if imaging shows brain lesions disseminated in space and time)
• Radiologically active disease defined by at least one gadolinium-enhancing lesion on a T1-weighted magnetic resonance imaging brain scan performed recently (i.e. within 3 months prior to inclusion)
• Disease-modifying drug naïve patients or patients with stable and adequately taken disease-modifying therapy (interferon ß-1, glatiramer acetate, or dimethyl fumarate) for at least six months before inclusion (NOTE: Other disease modifying drugs might be added at a later date, depending on the results of current investigations)
• EDSS Score ? 5.5
• Positive predictive test in vitro for patient’s CD4+ cell reactivity to immunogenic peptide
• Women of childbearing age must have a negative pregnancy test and must use adequate contraception during the treatment and follow-up phase of the study
• Fully informed written consent obtained

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 18
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Positive only for the HLA DRB1*0101, DRB1*0102, DRB1*0401, DRB1*0426 alleles or for the combination of the previous alleles.
• Evidence of clinical relapse and use of intravenous or oral corticosteroids within 30 days prior to inclusion
• Therapeutic escalation anticipated (including change of disease modifying drug), other than the cell-based immunotherapy of this study, within the next six months
• Significant coexisting systemic disease including renal insufficiency
• Positive serology for hepatitis B and C, AIDS and syphilis
• Participation in another interventional clinical study, currently or during the past three months




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Multiple sclerosis is an immune-mediated inflammatory disease that attacks myelinated axons in the central nervous system. MS is characterized initially by episodes of reversible neurologic deficits. In most patients, these episodes are followed by progressive neurologic deterioration over time. Relapsing-remitting multiple sclerosis is characterized by recurrent attacks of neurologic dysfunction (relapses) followed by periods of complete or incomplete recovery (remission)
MedDRA version: 18.1 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: SCLEROLYM
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Cytolytic CD4+ T cells
Other descriptive name: AUTOLOGOUS T-LYMPHOCYTES
Concentration unit: million organisms/ml million organisms/millilitre
Concentration type: range
Concentration number: 5-50

Primary Outcome(s)

Primary end point(s): Primary endpoint is safety. Safety will be evaluated with the help of the following parameters:
• AEs (baseline + treatment and follow-up phases)
• Vital signs
• Physical examination
• Laboratory parameters
• MRI
In accordance with the EMA Guideline on clinical investigation of medicinal products for the treatment of multiple sclerosis, special attention will be given to the occurrence of neurological adverse events or exacerbations of neurological symptoms as well as to the possible appearance of diseases related to immunosuppression. The requirement for comprehensive data on clinical and/or MRI rebound after discontinuation of the study drug does not apply to this study characterized by a single infusion of CD4+ cells.

Main Objective: The primary objective is to evaluate the safety of a treatment with autologous CD4+ cells, stimulated and expanded ex vivo by a myelin oligodendrocyte glycoprotein peptide modified by the introduction of a thioreductase motif into the flanking residues of the T cell epitope by means of AE reports, vital signs, physical examination, and laboratory evaluation

Timepoint(s) of evaluation of this end point: D-90, D0 (administration of the IMP), D45, D90, D180

Secondary Objective: Efficacy of the cell based immunotherapy on magnetic resonance imaging (MRI) variables, Expanded Disability Status Scale (EDSS) score, clinical relapses, and specific biomarkers (circulating MOG specific cytolytic CD4+ cells (identified by specific markers) and circulating anti-MOG antibodies)

Secondary Outcome(s)

Secondary end point(s): Efficacy parameters are secondary endpoints and include:
• MRI
• Disability: EDSS score
• Clinical relapses
• Biomarkers: Circulating MOG specific cytolytic CD4+ cells and circulating anti-MOG antibodies

Timepoint(s) of evaluation of this end point: D-90, D-45 (only MRI), D0 (administration of the IMP), D45, D90, D135, D180

Secondary ID(s)

MS/MOGMOD/CT/FIH/01

Source(s) of Monetary Support

ImCyse