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HomeResearch   Participate in Research Studies   Participate in a Clinical Trial

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Participate in a Clinical Trial

Without the participation of people with MS, it would be impossible to develop new and better therapies and other interventions.

Clinical Trial Finder

Search Results

Safety and Efficacy of CT103A Cells for Relapsed/Refractory Antibody-associated Inflammatory Diseases of the Nervous System

Study Purpose

Antibody-mediated inflammatory diseases of the nervous system (also known as autoimmune diseases of the nervous system) are autoimmune diseases in which autoimmune cells and immune molecules attack the nervous system as the main pathogenic mechanism. In the immune response, pathogenic antibodies acting on autoantigens of the nervous system are collectively referred to as autoantibodies of the nervous system, and antibody-mediated inflammatory diseases of the nervous system can occur in the central nervous system, peripheral nervous system, and neuromuscular junctions, and muscles. In this study, we will recruit eight kinds of autoimmune diseases of nervous system including Neuromyelitis Optica Spectrum Disorder (NMOSD), Myasthenia Gravis (MG), Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP), idiopathic inflammatory myopathyand (IIM), multiple sclerosis (MS), autoimmune encephalitis (AE), Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) and POEMS Syndrome. B-cell maturation antigen (BCMA) is expressed on the surface of plasma cells, thus making it an ideal target for targeted therapies. Chimeric antigen receptor (CAR) T cells against BCMA offers another potential therapeutic option to eliminate plasma cells in patients with neurological autoimmune diseases driven by abnormal antibody who still suffer recurrent attacks from conventional treatments. In the current study, the safety and efficacy of a novel CAR-T cell therapy using CT103A cells, are evaluated in patients with relapsed/refractory antibody-mediated idiopathic inflammatory diseases.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years - 75 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Male or female subjects aged 18-75 years (including 18 and 75 years); 2. Subjects with Relapsing/refractory Antibody-mediated inflammatory diseases of the nervous system without effective treatment, including: 1. Subjects must be diagnosed as AQP4-IgG-positive NMOSD defined by 2015 criteria of IPND NMOSD and meet the following requirements: i. At least one kind of immunosuppressant has been used for more than one year with poorly-controlled symptoms; ii. Clinical evidence of at least two relapses in the last 12 months or three relapses in the last 24 months and one relapse in the preceding 12 months before screening. 2. Subjects with MG with positive abnormal antibody, MG-ADL total score ≥ 6 points, MGFA classification II-IV defined by 2020 MGFA diagnostic criteria and meet the following requirement: i. At least one kind of immunosuppressant for standardized treatment for more than 1 year, and have one of the following poor control conditions: 1) continuous inability to affect daily life; 2) Exacerbation of MG symptoms and/or crisis attacks still occur despite standard treatment; 3) Inability to tolerate immunosuppressive therapy ii. Requires plasma exchange or maintenance therapy with IV gamma globulin. 3. Subjects with CIDP with positive abnormal antibodies, INCAT disability scale with total score of 2-9 defined by 2021 EAN/PNS diagnostic criteria and meet the following requirement: i. Standardized use of at least one first-line therapy for more than 3 months (cortisol hormone therapy, gamma globulin or plasma exchange therapy) with poorly-controlled symptoms. ii. Inability to tolerate cortisol hormones, gamma globulin, and plasmapheresis because of side effects or other conditions. 4. Subjects were diagnosed with IIM defined by 2017 European League against Rheumatism/American Rheumatology (EULAR/ACR) conference Class criteria; At least one kind of cardiac enzymes (CK, AST, ALT, ALD, LDH) ≥1.5×ULN during the screening period, or Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) ≥6, or at least one other sign of active disease within the last 6 months: MRI, EMG, or muscle biopsy; positive serological tests for myositis-specific antibodies (MSA) or myositis-associated autoantibodies (MAA), or antinuclear antibody (ANA). and meet one of the following requirements: i. After at least 1 month of corticosteroid therapy and standardized use of at least one immunosuppressant/modulator (eg, azathioprine, methotrexate, mycophenolate mofetil, cyclosporine, tacrolimus, Cyclophosphamide, leflunomide, intravenous gamma globulin, etc.) for more than 3 months with poorly-controlled symptoms. ii. ii. Inability to tolerate the above traditional regimens due to side effects or other conditions; e. Subjects were diagnosed with PMS (including PPMS and SPMS) or RMS according to the 2017 revision of the McDonald diagnostic criteria;EDSS score between 2 to 7 points inclusive, at screening. Subjects with RMS should meet one of the following requirements after standard therapy: i. at least two relapses in the last two years before screening. ii. at least one relapse in the last one year before screening. iii. positive Gd-enhancing MRI in the last one year before screening. f. Subjects were diagnosed with POEMS syndrome according to the 2021 revised IMWG diagnostic criteria and meet all of the following requirements: i. bone marrow involvement; ii. no response to traditional regimens treatment including corticosteroid, chemotherapy, protease inhibitor or inability to tolerate the above traditional regimens; iii. Have measurable lesions (refer to the 2021 revised IMWG standard) iv. VEGF > 2 ULN; v. ECOG score ≥1; vi. ONLS score ≥1. g. Subjects were diagnosed with autoimmune encephalitis according to the 2016 International Diagnostic Criteria for Autoimmune Encephalitis and meet all of the following requirements: i. at least one pathogenic antibody positive; ii. previously standardized use of corticosteroid, at least one immunosuppressant/modulator, including CD20 monoclonal antibody with poorly-controlled symptoms or intolerance; iii. onset of autoimmune encephalitis within 3 months prior to screening; iv. mRS Score ≥2 or CASE score ≥4. h. Subjects were diagnosed with MOGAD according to the 2023 International MOGAD Diagnostic criteria and meet all of the following requirements: i. a documented positive serum MOG Ab test using a cell-based assay (CBA); ii mRS Score ≥2; iii previously standardized use of corticosteroid, at least one immunosuppressant/modulator, including CD20 monoclonal antibody with poorly-controlled symptoms or intolerance. 3. All acute toxic reactions resolved to baseline or ≤ grade 1 assessed using NCI-CTCAE v5.0 except the ones adjudicated by the investigator to pose no risks on subjects. 4. Enrolled subjects must have satisfactory organ function and laboratory findings as defined by the following:i. Blood tests: absolute neutrophil count ≥ 2×109/L (or normal lower limit set by the central lab of the institution), platelets ≥ 100 × 109/L, and hemoglobin ≥ 100 g/L; ii. Liver function: total serum bilirubin, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be ≤ 1.5x the institutional normal upper limit (ULN); iii. Kidney function: CrCl ≥ 60 ml/min/1.73m2 (according to the following Cockcroft-Gault formula); iv. Electrolytes: blood potassium ≥ 3.0 mmol/L; blood calcium ≥ 2.0 mmol/L, blood magnesium ≥ 0.5 mmol/L; v. Coagulation function: fibrinogen ≥ 1.0 g/L; APTT ≤ ULN + 10s; PT ≤ ULN + 3s. 5. Blood oxygen saturation > 91% in resting state. 6. Echocardiography suggests LVEF≥ 50%. 7. Expected life expectancy ≥ 12 weeks as assessed by the investigator. 8. After signing the informed consent form, subjects and their partners must be willing to use effective and reliable method of contraception, devices or medicines, within one year after CT103A cells infusion (excluding contraception safety periods). 9. Subjects must provide written informed consent before the study begin.

Exclusion Criteria:

1. Patients do not have adequate mononuclear cells without mobilization for CAR-T cell manufacturing. 2. History of autoimmune hemolytic disease. 3. History of solid organ transplantation. 4. Patients were treated with alemtuzumab within 6 months prior to apheresis. Patients were treated with fludarabine or cladribine within 3 months prior to apheresis. 5. Patients with Papovaviruses infection. 6. Patients have been diagnosed with malignancies in the last 2 years prior to screening except for non-melanoma skin cancer, stage I cancers with complete resection and low risk of relapse, localized prostate cancer post-treatments, biopsy-confirmed in situ cervical cancer, or squamous epithelial lesion by PAP smear. 7. Chronic and active hepatitis B (HBV), hepatitis C (HCV), Human Immunodeficiency Virus (HIV) infection, CMV or syphilis infections concurrently. 8. MG crisis was not effectively controlled within 2 weeks before enrollment. 9. Known history of primary immunodeficiency (innate or acquired). 10. Patients with severe impaired cardiac function, including but not limited to the following: unstable angina, myocardial infarction (within 6 months before enrollment), congestive heart failure (≥Grade III by NYHA), severe ventricular arrhythmia. 11. Cerebrovascular accidents, including transient ischemic attack or stroke history, occurred within 6 months before enrollment. 12. Major operation or surgical treatment caused by any reason within 4 weeks before enrollment. 13. Any serious and/or uncontrolled comorbidities which may interfere with the evaluation during the study in the opinion of the investigator. 14. Previous treatments: History of thymectomy within 12 months prior to CT103A infusion; 15. History of psychoactive drug abuse and failed to withdraw, or have a history of psychiatric disorders. 16. Prone to allergies or history of serious allergy. 17. Pregnant or lactating women. 18. Patients with other conditions adjudicated by the investigator as unsuitable for enrollment. Criteria for lymphodepletion and CAR-T cells infusion: Before lymphocyte depletion and CAR-T cells infusion, patients are evaluated and those meeting the following criteria cannot be included: 1. Blood tests: neutrophil count < 2 × 109/L, platelet count < 50 × 10^9/L; 2. Oxygen inhalation is required to maintain blood oxygen saturation ≥ 91%; 3. Patients have the following conditions, including but not limited to: new arrhythmia cannot be controlled by drugs; hypotension requiring pressor drugs; bacterial, fungal or viral infection requiring intravenous antibiotic treatment; creatinine clearance rate < 50 ml/min ; 4. Patients require maintenance support treatment within one week to meet the criteria for lymphodepletion or CAR T cell infusion. 5. Cell infusion is delayed > 7 days after lymphodepletion for any reason; 6. Patients with other conditions adjudicated by the investigator as unsuitable for lymphodepletion or cell infusion.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04561557
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Early Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Tongji Hospital
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Wei Wang, MD
Principal Investigator Affiliation Tongji Hospital
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, Industry
Overall Status Recruiting
Countries China
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Autoimmune Diseases, Autoimmune Diseases of the Nervous System, Neuromyelitis Optica Spectrum Disorder, Myasthenia Gravis, Chronic Inflammatory Demyelinating Polyradiculoneuropathy, Idiopathic Inflammatory Myopathies, Multiple Sclerosis, Autoimmune Encephalitis, Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD), POEMS Syndrome
Arms & Interventions

Arms

Experimental: CAR T cells therapy,Dose level 1: 0.5 × 10^6 CAR-T cells/Kg

The tolerability and safety of CT103A cells will be assessed in an initial dose of 0.5×10^6 CAR-T cells/Kg and three subjects will be enrolled firstly. If no dose-limiting toxicity (DLT) occurs and at least one subject benefits from the treatment, there will be two options for the investigator based on the available data: 1) three more subjects will be enrolled in the 0.5 × 10^6 CAR-T cells/Kg group and DLT will be evaluated in a total of six subjects; 2) another three subjects will be treated with 1 × 10^6 CAR-T cells/Kg instead of 0.5 × 10^6 CAR-T cells/Kg. If DLT occurs in one of the first three subjects, three more subjects will be enrolled in this cohort to reach the total subjects of six.

Experimental: CAR T cells therapy,Dose level 2: 1 × 10^6 CAR-T cells/Kg

If neither DLT nor efficacy is shown in the first three subjects, the dose of CAR-T cells will be increased to 1 × 10^6 CAR-T cells/kg to assess DLT.

Experimental: CAR T cells therapy,Dose level 3: 0.25 × 10^6 CAR-T cells/Kg

If DLT occurs in two subjects, whether to test the safety and efficacy in 0.25 × 10^6 CAR-T cells/kg group will be determined by the investigator based on the initial data of efficacy, PK and PD.

Interventions

Biological: - CT103A cells

Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) to manufacture CT103A cells, during which cyclophosphamide will be administered for the purpose of lymphocytes depletion. After lymphodepletion, subjects will receive one dose treatment with CT103A cells by intravenous (IV) infusion. The initial dose of 0.5×10^6 CAR+ T cells/kg will be infused on day 0.

Drug: - Cyclophosphamide and fludarabine

Subjects will receive one 3-day cycle of lymphodepletion starting 4 days prior to CT103A infusion on Day 0. Subjects will be given IV infusion of cyclophosphamide 300 mg/m2/day on day -4, -3 and -2, and fludarabine 30 mg/m2 over 30 minutes administered immediately after cyclophosphamide.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Wuhan, Hubei, China

Status

Recruiting

Address

Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology

Wuhan, Hubei, 430000

Site Contact

Chuan Qin, PhD

[email protected]

86-27-83663337

Nearest Location

Site Contact

Chuan Qin, PhD

[email protected]

86-27-83663337


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The content provided on clinical trials is for informational purposes only and is not a substitute for medical consultation with your healthcare provider. We do not recommend or endorse any specific study and you are advised to discuss the information shown with your healthcare provider. While we believe the information presented on this website to be accurate at the time of writing, we do not guarantee that its contents are correct, complete, or applicable to any particular individual situation. We strongly encourage individuals to seek out appropriate medical advice and treatment from their physicians. We cannot guarantee the availability of any clinical trial listed and will not be responsible if you are considered ineligible to participate in a given clinical trial. We are also not liable for any injury arising as a result of participation.

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