Safety and Efficacy of CT103A Cells for Relapsed/Refractory Antibody-associated Inflammatory Dise… (NCT04561557) | Clinical Trial Compass
RecruitingEarly Phase 1
Safety and Efficacy of CT103A Cells for Relapsed/Refractory Antibody-associated Inflammatory Diseases of the Nervous System
China36 participantsStarted 2020-09-22
Plain-language summary
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.
Who can participate
Age range18 Years – 75 Years
SexALL
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Inclusion criteria
✓. Male or female subjects aged 18-75 years (including 18 and 75 years);
✓. Subjects with Relapsing/refractory Antibody-mediated inflammatory diseases of the nervous system without effective treatment, including:
✓. 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.
✓. 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
✓. 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
What they're measuring
1
Types and incidence of dose-limiting toxicity (DLT) after CT103A cells infusion
Timeframe: Up to 28 days post CT103A infusion
2
Incidence and severity of AEs, including changes in vital signs, physical examination, laboratory parameters, Electrocardiograms and Echocardiograms.
✓. 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:
✓. 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.
✓. 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.
Exclusion criteria
✕. Patients do not have adequate mononuclear cells without mobilization for CAR-T cell manufacturing.
✕. History of autoimmune hemolytic disease.
✕. History of solid organ transplantation.
✕. Patients were treated with alemtuzumab within 6 months prior to apheresis. Patients were treated with fludarabine or cladribine within 3 months prior to apheresis.
✕. Patients with Papovaviruses infection.
✕. 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.
✕. Chronic and active hepatitis B (HBV), hepatitis C (HCV), Human Immunodeficiency Virus (HIV) infection, CMV or syphilis infections concurrently.
✕. MG crisis was not effectively controlled within 2 weeks before enrollment.