This is an early exploratory study to assess the tolerability and safety of GC012F CAR T cell injection in Multiple Sclerosis patients.
This is a single-arm, open-label, early exploratory clinical study to evaluate the safety and efficacy of GC012F Injection with or without Lymphocyte Depletion (LD) pretreatment in patients with MS, as well as to assess its PK and PD profiles. This study consists of the following periods: screening period, apheresis day, baseline period(if applicable), lymphodepletion preconditioning period, GC012F infusion, safety and efficacy follow-up period, and long-term follow-up period. This study consists of three phases: Stage A (Lymphocyte Depletion group ),stage B(Without (Lymphocyte Depletion group) and stage C (expansion period): Stage A (Lymphocyte Depletion group ):Three evaluable participants were enrolled and received a single dose CAR-T cell infusion, in combination with a Lymphocyte Depletion pre-treatment regimen, in order to establish the initial safety profile of this treatment. Stage B(Without Lymphocyte Depletion group) :Three evaluable participants were enrolled and received a single dose CAR-T cell infusion,in combination without a Lymphocyte Depletion pre-treatment regimen,To assess the necessity of combining Lymphocyte Depletion pre--treatment. stage C (expansion period):Enrolled up to 3 evaluable participants and received a single dose CAR-T cell infusion,According to the data of the early stage, consider whether to combine with Lymphocyte Depletion and pre-treatment. After the administration of GC012F, participants will be followed up for 3 years in this study, and then enter the long-term follow-up period to continue the long-term safety assessment and the persistence assessment of clinical response. The total follow-up period from the administration of GC012F is approximately 15 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
A single dose group is planned for the CAR-T cell infusion dose is administrated for each subject.Single IV infusion.
Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science & Technology
Hubei, Hubei, China
RECRUITINGDose-Limiting Toxicity (DLT) Rate
DLT is defined as an AE that occurs within 28 days of GC012F CAR-T product reinfusion.DLT will be evaluated according to NCI-CTCAE V5.0 criteria.
Time frame: 28 days
Adverse Events (AEs)Rate
Proportion of trial participants experiencing AE within 15 years after infusion of GC012F CAR-T cell injection.
Time frame: Up to 15 years from treatment discontinuation
GC012F T cell count in peripheral blood and cerebrospinal fluid (CSF)(Pharmacokinetic evaluation indicators)
Maximum observed blood and CSF concentration, time to maximum observed blood and CSF concentration, area under the bloodand CSF concentration-time curve from time zero to 28 days after infusion, last observed measurable concentration, and time to last observed measurable CAR-T cell concentration
Time frame: Up to 36 months from treatment discontinuation
GC012F CAR gene copy number in peripheral blood and cerebrospinal fluid (CSF)(Pharmacodynamic evaluation indicators,)
Observe blood and CSF the highest concentration of the CAR gene copy number
Time frame: Up to 36 months from treatment discontinuation
Changes in the concentration of soluble B-cell maturation antigen (BCMA) in peripheral blood
Observe blood the highest concentration of the BCMA
Time frame: Up to 36 months from treatment discontinuation
Levels of Interleukins (IL-2, IL-6, IL-8, IL-10)
Observe blood the highest Quantification of the cytokines Interleukins (IL-2, IL-6, IL-8, IL-10)
Time frame: Up to 84 days from treatment discontinuation
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Iimmunoglobulins (Ig) levels in peripheral blood
Observe blood the highest Quantification of the immunoglobulins (Ig)
Time frame: Up to 15 years from treatment discontinuation
Concentration levels of neurofilament light chain protein in peripheral blood and cerebrospinal fluid (CSF)
Observe blood and CSF the highest concentration of neurofilament light chain protein
Time frame: Up to 15 years from treatment discontinuation
In kappa free light chain index levels in peripheral blood and cerebrospinal fluid CSF
Observe blood and CSF the highest concentration of t chain index
Time frame: Up to 36 months from treatment discontinuation
Percentage of trial participants developing antibodies against GC012F
Proportion of trial participants experiencing against GC012F within 15 years after infusion of GC012F CAR-T cell injection.
Time frame: Up to 15 years from treatment discontinuation
Annualized relapse rate in trial participants with relapsing-remitting multiple sclerosis (RRMS)
Defined to number of MS relapses after GC012F cell infusion divided by number of years of observation
Time frame: Up to 15 years from treatment discontinuation
Time to first relapse
Defined to Time from GC012F infusion to first MS relapse
Time frame: Up to 15 years from treatment discontinuation
Numbers of gadolinium (Gd)-enhancing T1 lesions
To evaluated number of gadolinium (Gd)-enhancing T1 lesions in magnetic resonance imaging (MRI) metrics from baseline
Time frame: Up to 15 years from treatment discontinuation
Numbers of new or definitely enlarged T2 lesions
To evaluated number of new or definitely enlarged T2 lesions in magnetic resonance imaging (MRI) from baseline
Time frame: Up to 15 years from treatment discontinuation
Total brain volume
To evaluated total brain volume in magnetic resonance imaging (MRI) metrics from baseline
Time frame: Up to 15 years from treatment discontinuation
Numbers and volume of paramagnetic rim lesions
To evaluated number and volume of paramagnetic rim lesions in magnetic resonance imaging (MRI) metrics from baseline
Time frame: Up to 15 years from treatment discontinuation
Expanded Disability Status Scale (EDSS) grade,ranges from 0 to 10 points.
The expanded disability status scale (EDSS) definition is a common method used to assess neurological dysfunction in MS, based on neurological findings to determine worsening and improvement of disability. Ranges from 0 points(no neurologic impairment) to 10 points (death due to Multiple Sclerosis ), at intervals of 0.5 points.
Time frame: Up to 15 years from treatment discontinuation
Deep gray matter volume
To evaluated deep gray matter volume in magnetic resonance imaging (MRI) metrics from baseline
Time frame: Up to 15 years from treatment discontinuation discontinuation
Cortical volume
To evaluated cortical volume in magnetic resonance imaging (MRI) metrics from baseline
Time frame: Up to 15 years from treatment discontinuation
Levels of Interferons-γ (IFN-γ)
Observe blood the highest Quantification of the cytokines Interferons-γ (IFN-γ)
Time frame: Up to 84 days from treatment discontinuation
Levels of Tumor Necrosis Factors α (TNF-α)
Observe blood the highest Quantification of the cytokines Tumor Necrosis Factors α(TNF-α)
Time frame: Up to 84 days from treatment discontinuation
Changes in Oligoclonal Band level in peripheral blood and cerebrospinal fluid CSF
Observe blood and CSF the highest concentration of oligoclonal band
Time frame: Up to 36 months from treatment discontinuation