A Trial for Evaluating Both Safety and Preliminary Efficacy of a Single Infusion of Stimulated Autologous CD4+T Cells in Patients With Relapsing- Remitting Multiple Sclerosis (SCLEROLYM)

A Clinical Trial to Document Safety and Radiological Disease Activity in Patients With Relapsing-remitting Multiple Sclerosis Treated With Autologous CD4+ T 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 Cell Epitope - A First-in-human Trial (SCLEROLYM TRIAL)

The purpose of this study is to assess the safety and the preliminary efficacy of a single infusion of stimulated autologous CD4+ T cells in patients with Relapsing-Remitting Multiple Sclerosis.

The study duration for the patients (from start of baseline to end of follow-up) is 270 days.

Study Overview

• Status: Terminated
• Conditions: Multiple Sclerosis, Relapsing-Remitting
• Intervention / Treatment: Biological: Autologous CD4+T cells stimulated and expanded ex vivo by a MOG peptide modified by the introduction of a thioreductase motif into the flanking residues of the T cell epitope

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1200
    • Cliniques universitaires Saint-Luc
  • Leuven, Belgium, 3000
    • University Hospital Leuven (Gasthuisberg)
  • Liège, Belgium, 4000
    • University Hospital of Liege

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females 18 to 60 years of age
• Patients closely followed up for at least one year prior to inclusion (i.e. prior to the start of the baseline phase) if the diagnosis of the disease was made more than one year ago, to ensure that all possible episodes of clinical relapses which occurred during this interval of time were recorded and documented
• 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 β-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 (three pregnancy tests will be required prior to and during the study: (1) during the screening phase, (2) about one week prior to leukapheresis, and (3) about one week prior to re-infusion of autologous cells)
• Fully informed written consent obtained

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: IMP	Biological: Autologous CD4+T cells stimulated and expanded ex vivo by a MOG peptide modified by the introduction of a thioreductase motif into the flanking residues of the T cell epitope; 1 administration comprising 5 - 50 millions of cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of the cell based immunotherapy (Adverse events)	Adverse events	6 months
Safety of the cell based immunotherapy (Vital signs)	Vital signs	6 hours
Safety of the cell based immunotherapy (Physical examination)	Physical examination	6 months
Safety of the cell based immunotherapy (Laboratory parameters)	Laboratory parameters	6 months
Safety of the cell based immunotherapy (MRI)	MRI	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI derived parameters	Cumulative number and mean number per scan of active inflammatory lesions; Cumulative number and mean number per scan of new lesions; Cumulative number and mean number per scan of enlarged lesions	3 months before the day of administration of the investigational medicinal product, the day of administration, 45, 90, 135 and 180 days after the administration
Expanded Disability Status Scale (EDSS)		3 months before the day of administration of the investigational medicinal product, the day of administration, 45, 90, 135 and 180 days after the administration
Clinical relapses		3 months before the day of administration of the investigational medicinal product, the day of administration, 45, 90, 135 and 180 days after the administration
Circulating MOG specific cytolytic CD4+ cells		3 months before the day of administration of the investigational medicinal product, the day of administration, 45, 90, 135 and 180 days after the administration
Circulating anti-MOG antibodies		3 months before the day of administration of the investigational medicinal product, the day of administration, 45, 90, 135 and 180 days after the administration

Collaborators and Investigators

• Sponsor: Imcyse SA

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: April 2, 2015
• First Submitted That Met QC Criteria: April 27, 2015
• First Posted (Estimate): April 28, 2015

Study Record Updates

• Last Update Posted (Actual): August 22, 2017
• Last Update Submitted That Met QC Criteria: August 18, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting
• Other Study ID Numbers: MS/MOGMOD/CT/FIH/01