Clareo Health | Safety and Pharmacodynamics of QH103 Cell Injection in the Treatment of Patients With Relapsed/Refractory Antibody-Mediated Neurological Autoimmune Diseases.
Safety and Pharmacodynamics of QH103 Cell Injection in the Treatment of Patients With Relapsed/Refractory Antibody-Mediated Neurological Autoimmune Diseases.
2. Female subjects of childbearing potential and male subjects with partners of childbearing potential must use medically approved contraception or practice abstinence during the study treatment period and for at least 6 months after the end of the study treatment. Female subjects of childbearing potential must have a negative serum HCG test within 7 days before study enrollment and must not be breastfeeding.
3. The subject's expected survival, as judged by the investigator, is ≥12 weeks.
4. Voluntarily participate in this trial and sign the informed consent form.
1、Multiple Sclerosis (MS): Clinically confirmed as progressive MS (including Primary Progressive PPMS or Secondary Progressive SPMS) or Relapsing-Remitting MS (RMS) according to the revised 2017 McDonald criteria. Disability status at screening must meet an EDSS score of 2-7 (inclusive) .For participants with RMS, despite standardized use of DMTs, they must have documented evidence meeting one of the following conditions prior to signing the informed consent:
1. Two relapses were recorded within the first 2 years of screening;
2. One recurrence was recorded within the first year prior to screening;
3. Select the results of Gd-enhanced MRI scans that were positive within the previous year (if there is no record of a positive Gd-enhanced scan in the previous year, the results of the screening MRI scan can be used).
2、Neuromyelitis Optica Spectrum Disorder (NMOSD): Participants with AQP4 antibody-positive NMOSD meeting the 2015 IPND NMOSD diagnostic criteria, and meeting one of the following:
1. Treatment with at least one immunosuppressant for over 1 year, or intolerance to immunosuppressant treatment, with suboptimal symptom control.
2. At least 2 documented relapses within the last 12 months, or 3 documented relapses within the last 24 months with at least 1 relapse occurring within the 12 months prior to screening.
3、Autoimmune Encephalitis (AE): Participants with a clinical diagnosis of Autoimmune Encephalitis based on the 2016 International Diagnostic Criteria, meeting all of the following requirements:
1. Positive for at least one relevant autoantibody;
2. Inadequate symptom control with or intolerance to previous standardized treatment with glucocorticoids and at least one immunosuppressant/immunomodulator (including CD20 monoclonal antibody);
3. An episode of autoimmune encephalitis within 3 months prior to signing the informed consent form;
4. Disability status at screening meeting a modified Rankin Scale (mRS) score ≥ 2 or a CASE score ≥ 4 .
4、Chronic Inflammatory Demyelinating Polyneuropathy (CIDP): Participants diagnosed with antibody-positive CIDP according to the 2021 EAN/PNS diagnostic criteria, with an INCAT Disability Scale total score between 2 and 9, and meeting one of the following:
1. Inadequate symptom control despite standardized use of at least one first-line therapy (corticosteroids, intravenous immunoglobulin, or plasma exchange) for over 3 months;
2. Intolerance to corticosteroids, intravenous immunoglobulin, and plasma exchange due to side effects or other reasons.
5、Myasthenia Gravis (MG): Participants diagnosed with antibody-positive MGFA Class II-IV Myasthenia Gravis according to the 2020 MGFA diagnostic criteria, with a Myasthenia Gravis Activities of Daily Living (MG-ADL) profile (Appendix 6) total score ≥ 6, and meeting one of the following:
1. Standardized treatment with at least one immunosuppressant for over 1 year, with one of the following indicating inadequate control: (1) persistent weakness affecting daily life, (2) worsening MG symptoms and/or crisis episodes despite standard treatment, or (3) intolerance to immunosuppressant therapy;
2. Requiring maintenance therapy with plasma exchange or intravenous immunoglobulin.
6、Anti-Myelin Oligodendrocyte Glycoprotein Immunoglobulin G Antibody----- - Associated Disease (MOGAD): Participants with a clinical diagnosis of MOGAD based on the 2023 International MOGAD Diagnostic Criteria, meeting all of the following:
1. Positive for MOG autoantibody via cell-based assay (CBA);
2. Disability status at screening meeting a modified Rankin Scale (mRS) score ≥ 2.
3. Inadequate symptom control with or intolerance to previous standardized treatment with glucocorticoids and at least one immunosuppressant / immunomodulator (including CD20 monoclonal antibody).
7、Idiopathic Inflammatory Myopathies (IIM): Patients clinically diagnosed with refractory, antibody-positive Idiopathic Inflammatory Myopathy (IIM) based on the 2017 European Alliance of Associations for Rheumatology/American College of Rheumatology (EULAR/ACR) classification criteria. At screening, at least one muscle enzyme (CK, AST, ALT, ALD, LDH) must be ≥1.5 times the upper limit of normal (ULN); OR the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) for dermatomyositis must be ≥6 (Appendix 7); OR there must be evidence of active myositis within the last 6 months from at least one of the following: MRI, electromyography, or muscle biopsy. The patient must test positive for at least one myositis-specific antibody (MSA), myositis-associated antibody (MAA), or antinuclear antibody (ANA). Additionally, they must meet one of the following criteria:
1. Treatment with corticosteroids for at least 1 month, combined with standardized use of at least one immunosuppressant/immunomodulator (e.g., azathioprine, methotrexate, mycophenolate mofetil, cyclosporine, tacrolimus, cyclophosphamide, leflunomide, intravenous immunoglobulin, etc.) for over 3 months, resulting in inadequate symptom control.
2. Intolerance to the aforementioned conventional treatment regimens due to side effects or other reasons.
You may not be if
1. History of severe drug allergy or allergic diathesis.
2. Presence of or suspected uncontrolled or treatment-requiring fungal, bacterial, viral, or other infections.
3. Organ function that does not meet the following requirements (except for abnormalities caused by the autoimmune disease itself):
1. Bone Marrow Function: White blood cell count ≥1×10⁹/L; absolute neutrophil count ≥1×10⁹/L (no treatment with colony-stimulating factors within 2 weeks prior to the test); hemoglobin ≥60 g/L.
2. Liver Function: ALT ≤3×ULN (except if elevated due to inflammatory myopathy); AST ≤3×ULN (except if elevated due to inflammatory myopathy); Indirect bilirubin (IBIL) ≤1.5×ULN (except for Gilbert's syndrome); Total bilirubin ≤3.0×ULN.
3. Renal Function: Creatinine clearance (CrCl) ≥30 mL/min (eGFR ≥30 mL/min/1.73m²) (calculated by Cockcroft-Gault formula, except for acute decreases in CrCl due to the disease itself).
4. Coagulation Function: International normalized ratio (INR) ≤1.5×ULN; Prothrombin time (PT) ≤1.5×ULN.
5. Cardiac Function: Left ventricular ejection fraction (LVEF) ≥55% and no clinically significant cardiac disease.
4. Subjects with a history indicative of congenital immunoglobulin deficiency.
5. History of active/unresolved malignant tumors within the past 5 years.
6. Subjects who are positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA titer above the detection limit; positive for hepatitis C virus (HCV) antibody with detectable peripheral blood HCV RNA; positive for human immunodeficiency virus (HIV) antibody; or positive for Treponema pallidumserology.
7. History of definite psychiatric disorders or history of substance abuse involving psychotropic drugs that cannot be discontinued.
8. Participation in any other clinical trial within 3 months prior to enrollment.
9. Prior treatment with CAR-T cell therapy.
10. History of severe adverse reactions to cyclophosphamide or fludarabine.
11. History of other autoimmune diseases (e.g.,Crohn's disease, systemic lupus erythematosus) that, within the past 2 years, have resulted in end-organ damage or required systemic immunosuppressive therapy (excluding the disease populations specified for enrollment in the study protocol).
12. Myasthenia gravis crisis not effectively controlled within 2 weeks prior to enrollment.
13. History of cerebrovascular accident, including transient ischemic attack or stroke, within 6 months prior to enrollment.
14. Male or female participants unwilling to practice contraception from the time of informed consent until 6 months after treatment completion.
15. Any medical condition that may interfere with the assessment of the safety or efficacy of the study treatment.
16. History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months prior to enrollment, requiring systemic anticoagulation therapy.
17. Any other condition that, in the investigator's judgment, makes the subject unsuitable for participation in this study.
