An Open-Label Study to Assess the Safety and Efficacy of GC012F in Patients With Multiple Sclerosis
Overview
- Phase
- Early Phase 1
- Status
- Not yet recruiting
- Sponsor
- Huashan Hospital
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- Dose-Limiting Toxicity (DLT) Rate
Overview
Brief Summary
This is an open-label,early-stage exploratory clinical study to evaluate the safety and preliminary efficacy of GC012F CAR T cell injection in Multiple Sclerosis subjects.
Detailed Description
This is a single-arm, open-label, early exploratory clinical study to evaluate the safety and efficacy of GC012F Injection in subjects 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, lymphodepletion preconditioning period, GC012F infusion, safety and efficacy follow-up period, and long-term follow-up period.
In this study, a single dose group is planned for the CAR-T cell infusion dose,and 15 evaluable subjects will be included. Eligible subjects will receive a single infusion of GC012F Injection and will be monitored for DLTs within 28 days following the infusion of GC012F Injection.
After all the 6 subjects have completed DLT observation, all clinical study safety data collected during the DLT observation phase will be assessed. 9 subjects will be enrolled in the dose expansion phase.
After CAR-T cell infusion, subjects will be followed up for safety, cell proliferation and survival, and efficacy until 672 days (96 weeks) after infusion, withdrawal from the study, death, withdrawal of informed consent, or lost to follow-up, whichever occurs first.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •1.Subjects or their legal representatives voluntarily sign a written informed consent form and are willing and able to comply with the procedures of this study;
- •2.Age 18 to 75 years (inclusive) at the time of signing the ICF, regardless of gender;
- •3.Women of childbearing potential must (women who have had a hysterectomy or have been postmenopausal for at least 2 years are not considered to be of potential childbearing potential):
- •a) At screening, the result of serum β human chorionic gonadotropin pregnancy test is negative;
- •b) Agree to refrain from breastfeeding for the duration of study participation until at least 2 years after GC012F injection infusion or until 2 consecutive flow cytometry tests show no more CAR-T cells (whichever occurs later);
- •4\. Male subjects with sexual partners and female subjects of potential childbearing potential agree to use highly effective contraceptive methods (e.g.: birth control pills, intrauterine devices, or condoms) from screening until then GC012F injection is no longer present for at least 2 years after infusion or until 2 consecutive flow cytometry tests show no more In CAR-T cells (whichever occurs later). Male subjects must agree to use a condom during sexual contact with a pregnant woman or a woman of childbearing potential for at least 2 years after GC012F injection infusion, even after a successful vasectomy;
- •5\. The venous access required for collection can be established, and there are no contraindications to leukocyte collection;
- •6.The laboratory test results at screening must meet the following criteria:
- •Organ and bone marrow function:
- •a)Absolute neutrophil count ≥ 1.0 × 10\^9/L (no growth factor is given for supportive care within 7 days prior to testing);
Exclusion Criteria
- •1.Have received any investigational drug treatment within 3 months prior to screening or within 5 half-lives (whichever is longer);
- •2.Fungal, bacterial, viral, or other infection not controlled and/or requiring hospitalization or intravenous antimicrobial therapy within 4 weeks prior to screening. Uncomplicated urinary tract infection and uncomplicated bacterial pharyngitis are permitted if responding to current therapy;
- •3.Active tuberculosis or latent tuberculosis that has not been treated appropriately prior to screening;
- •4.History of severe hypersensitivity or allergy;
- •5.Primary immunodeficiency;
- •6.Impaired cardiac function or clinically significant cardiac disease;
- •7.History of serious respiratory diseases or current serious respiratory diseases, including moderate or severe or above asthma or chronic obstructive pulmonary disease, interstitial lung disease, or pulmonary fibrosis;
- •8.History of severe respiratory disease or current severe respiratory disease;
- •9.Current or history of cirrhosis;
- •10.History of Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus within the past 2 years, and the need for continuous use of systemic immunosuppressants/systemic disease-modifying drugs;
Arms & Interventions
GC012F CAR-T Cell Injection
GC012F CAR-T Cell Injection Arm
Intervention: GC012F CAR-T Cell Injection (Drug)
Outcomes
Primary Outcomes
Dose-Limiting Toxicity (DLT) Rate
Time Frame: 28 days
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
Adverse Events （AEs）Rate
Time Frame: Up to 15 years from treatment discontinuation
Proportion of subjects experiencing AE within 15 years after infusion of GC012F CAR-T cell injection.
Iimmunoglobulins (Ig) levels in peripheral blood
Time Frame: Up to 15 years from treatment discontinuation
Observe blood the highest Quantification of the immunoglobulins (Ig)
Secondary Outcomes
- Peak blood and CSF concentration(Cmax)(Pharmacokinetic evaluation indicators)(Up to 36 months from treatment discontinuation)
- GC012F CAR gene copy number in peripheral blood and cerebrospinal fluid (CSF)(Pharmacodynamic evaluation indicators,)(Up to 36 months from treatment discontinuation)
- Changes in the concentration of soluble B-cell maturation antigen (BCMA) in peripheral blood(Up to 36 months from treatment discontinuation)
- Levels of Interleukins (IL-2, IL-6, IL-8, IL-10)(Up to 84 days from treatment discontinuation)
- Levels of Interferons-γ (IFN-γ)(Up to 84 days from treatment discontinuation)
- Levels of Tumor Necrosis Factors α (TNF-α)(Up to 84 days from treatment discontinuation)
- Concentration levels of neurofilament light chain protein in peripheral blood and cerebrospinal fluid (CSF)(Up to 15 years from treatment discontinuation)
- In kappa free light chain index levels in peripheral blood and cerebrospinal fluid CSF(Up to 36 months from treatment discontinuation)
- Percentage of subjects developing antibodies against GC012F(Up to 15 years from treatment discontinuation)
- Annualized relapse rate in subjects with relapsing-remitting multiple sclerosis (RRMS)(Up to 15 years from treatment discontinuation)
- Time to first relapse(Up to 15 years from treatment discontinuation)
- Numbers of gadolinium (Gd)-enhancing T1 lesions(Up to 15 years from treatment discontinuation)
- Numbers of new or definitely enlarged T2 lesions(Up to 15 years from treatment discontinuation)
- Total brain volume(Up to 15 years from treatment discontinuation)
- Cortical volume(Up to 15 years from treatment discontinuation)
- Deep gray matter volume(Up to 15 years from treatment discontinuation discontinuation)
- Numbers and volume of paramagnetic rim lesions(Up to 15 years from treatment discontinuation)
- Expanded Disability Status Scale (EDSS) grade,ranges from 0 to 10 points.(Up to 15 years from treatment discontinuation])
- Area under the plasma concentration versus time curve (AUC)(Pharmacokinetic evaluation indicators)(Up to 36 months from treatment discontinuation)
Investigators
Chao Quan
Professor
Huashan Hospital