New hope for rare bleeding disorder: experimental drug JCXH-213 enters human trials

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria 1. Voluntarily sign the informed consent form (ICF) and be expected to complete the follow-up visits and treatment required by the study protocol. 2. Age ≥ 18 years and ≤ 65 years at screening, male or female. 3. Clinical diagnosis of primary immune thrombocytopenia (ITP) for no less than 3 months, according to the American Society of Hematology 2011 Evidence-Based Practice Guideline (Neunert et al. 2011) or the International Consensus Report on the Investigation and Management of Primary Immune Thrombocytopenia (Provan et al. 2010), as applicable. Failure (ineffective, loss of maintenance of response, or relapse) of corticosteroid therapy and failure (ineffective, loss of maintenance of response, or relapse) or intolerance to at least one second-line ITP therapy. 4. At least one second-line ITP therapy includes: rituximab and/or recombinant human thrombopoietin (rhTPO, e.g., TPO), thrombopoietin receptor agonists (TPO-RA, e.g., eltrombopag, hetrombopag, avatrombopag, romiplostim). Ineffectiveness is defined as platelet count \< 30 × 10⁹/L after receiving the following treatments: Rituximab: 375 mg/m² once weekly for 4 doses; rhTPO: 300 U/kg/day for more than 14 days; Eltrombopag: 75 mg/day for more than 28 days; Hetrombopag: 7.5 mg/day for more than 28 days; Avatrombopag: 60 mg/day for more than 28 days; Romiplostim: up to a maximum weekly dose of 10 μg/kg for more than 28 days. 5. Platelet count \< 30 × 10⁹/L within 48 hours prior to the first dose of study drug (at least two consecutive platelet counts \< 30 × 10⁹/L, at least 1 day apart, during screening and/or prior to first dose). 6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2. 7. Patients receiving stable-dose maintenance therapy, including corticosteroids (not exceeding 0.5 mg/kg/day prednisone or equivalent) or thrombopoietin receptor agonists, may be enrolled, provided that the patient is on only one concomitant medication with stable dose and frequency, and the concomitant medication has been stable for at least 4 weeks prior to the first infusion of study drug. 8. Adequate organ function, meeting the following laboratory criteria: Coagulation function: Activated partial thromboplastin time (APTT) ≤ 1.5 × upper limit of normal (ULN) Prothrombin time (PT) ≤ 1.5 × ULN Liver function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN Total bilirubin ≤ 1.5 × ULN, unless documented Gilbert's syndrome Patients with Gilbert-Meulengracht syndrome may be included if total bilirubin ≤ 3.0 × ULN and direct bilirubin ≤ 1.5 × ULN Renal function: Serum creatinine ≤ 1.5 × ULN, or creatinine clearance ≥ 60 mL/min (Cockcroft-Gault formula; see Appendix 1) Hematology (without blood transfusion, platelet transfusion, or growth factor use within 7 days prior to screening hematology assessment): Hemoglobin ≥ 80 g/L Absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L Absolute lymphocyte count (LY) ≥ 0.5 × 10⁹/L Cardiopulmonary function: Left ventricular ejection fraction (LVEF) ≥ 45% Oxygen saturation ≥ 91% without supplemental oxygen 9. Female patients of childbearing potential must have a negative pregnancy test at screening. Any male or female patient of childbearing potential must agree to use effective contraceptive methods from the time of signing the ICF through at least 6 months after the last infusion of JCXH-213. Female patients not of childbearing potential must meet at least one of the following criteria: Have undergone hysterectomy, bilateral salpingectomy, or bilateral oophorectomy; Medically confirmed postmenopausal (at least 12 consecutive months of amenorrhea without pathological or physiological cause, with reproductive status assessed by hormone levels if necessary). Exclusion Criteria 1. Diagnosis of autoimmune hemolytic anemia, any secondary or hereditary thrombocytopenic disorders, including leukemia, lymphoma, multiple myeloma, aplastic anemia, myelodysplastic syndrome, Evans syndrome, common variable immunodeficiency, systemic lupus erythematosus, liver cirrhosis, antiphospholipid syndrome, pseudothrombocytopenia, or drug-induced thrombocytopenia (e.g., due to quinine, heparin, antibiotics, or antiepileptic drugs). 2. History of any thromboembolic event or extensive/severe bleeding within 1 year prior to the first dose of study drug, such as hemoptysis, major upper gastrointestinal bleeding, intracranial hemorrhage, or presence of sepsis or other irregular bleeding. 3. Receipt of anti-CD20 monoclonal antibody (e.g., rituximab) or other medicinal treatments (including cyclophosphamide and vindesine) within 3 months prior to the first dose of study drug. 4. Receipt of the following medicinal treatments within 4 weeks prior to the first dose of study drug: azathioprine, danazol, dapsone, cyclosporine A, tacrolimus, or sirolimus. 5. Use of anticoagulants or any antiplatelet agents (e.g., aspirin) within 3 weeks prior to the first dose of study drug. 6. Receipt of emergency treatment for ITP (e.g., methylprednisolone, platelet transfusion, intravenous immunoglobulin, or TPO-RA) within 2 weeks prior to the first dose of study drug. 7. Splenectomy within 6 months prior to the first dose of study drug. 8. History of malignancy within 5 years prior to screening, with the exception of adequately treated cervical carcinoma in situ, basal cell or squamous cell carcinoma of the skin, localized prostate cancer after radical surgery, ductal carcinoma in situ after radical surgery, or thyroid cancer after radical surgery. 9. Any unstable systemic disease, including but not limited to: uncontrolled active infection (excluding local infection); unstable angina pectoris; cerebrovascular accident or transient ischemic attack (within 6 months prior to screening); myocardial infarction or history of coronary angioplasty or stenting (within 6 months prior to screening); New York Heart Association (NYHA) Class III or IV cardiac insufficiency; refractory hypertension (defined as blood pressure not controlled after more than 1 month of treatment with ≥ 3 antihypertensive drugs \[including diuretics\] at reasonable and tolerable doses after lifestyle modification, or requiring ≥ 4 antihypertensive drugs to achieve blood pressure control); severe cardiac arrhythmia requiring medication; or significant hepatic, renal, or metabolic disease. 10. Known or suspected history of immunosuppression, including invasive opportunistic infections such as histoplasmosis, coccidioidomycosis, coccidiosis, Pneumocystis jirovecii pneumonia, and aspergillosis, even if the infection has resolved; or unusually frequent, recurrent, or prolonged infections, as judged by the investigator. 11. Positive peripheral blood test for hepatitis B virus (HBV) DNA; positive hepatitis C virus (HCV) antibody with positive peripheral blood HCV RNA; positive human immunodeficiency virus (HIV) antibody; positive cytomegalovirus (CMV) DNA; or positive Treponema pallidum test. 12. Prior receipt of organ transplantation, or planned organ transplantation during the study period. 13. Prior receipt of CAR-T therapy within 3 months. 14. Active autoimmune or inflammatory neurological disorder (e.g., Guillain-Barré syndrome, amyotrophic lateral sclerosis). 15. Clinically significant active cerebrovascular disease (e.g., cerebral edema, posterior reversible encephalopathy syndrome). 16. Life expectancy of less than 3 months. 17. Participation in another interventional clinical study and receipt of investigational drug within 1 month prior to enrollment (for marketed drugs, or investigational drugs with a known half-life, the shorter of 5 half-lives or 2 weeks applies). 18. Receipt of live attenuated vaccine within 6 weeks prior to screening, or planned receipt of live attenuated vaccine during the study period. 19. Contraindication or hypersensitivity to tocilizumab; contraindication or hypersensitivity to any component of the investigational product, JCXH-213. 20. Pregnant or lactating women, or women planning to become pregnant or breastfeed from the time of signing the ICF through 6 months after the last infusion of JCXH-213; or male patients whose partner plans to become pregnant during this period. 21. Any contraindication to any study procedure or other medical condition that, in the investigator's judgment and/or according to clinical standards, would place the patient at unacceptable risk.