[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"leadSponsorName\":\"Therorna\",\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:":72},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,2,0,[8,46],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":20,"targetDuration":4,"studyType":23,"phases":24,"briefSummary":26,"conditions":27,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":34,"lastUpdatePostDateStruct":35,"startDateStruct":38,"completionDateStruct":40,"leadSponsor":42,"locationsCount":45},"100624723","phase-1-a-clinical-study-of-ti-0032-iii-injection-in-patients-with-relapsed-and-refractory-autoimmune-diseases-100624723",false,"NCT07413341","A Clinical Study of TI-0032-III Injection in Patients With Relapsed and Refractory Autoimmune Diseases","A Clinical Study on the Safety and Efficacy of in Vivo CAR-T Cell Therapy (TI-0032-III Injection) for the Treatment of Relapsed and Refractory Autoimmune Diseases","in vivo CAR-T","Inclusion Criteria:\n\n* Understand trial procedures and methods, voluntarily sign the informed consent form .\n* Age ranges from 18 to 65 years old (including threshold), regardless of gender.\n* Positive expression of CD19 on peripheral blood B cells determined by flow cytometry.\n* Bone marrow function: neutrophil count ≥ 1.5 × 10\\^9\u002FL, lymphocyte count ≥ 0.8 × 10\\^9\u002FL, hemoglobin ≥ 90 g\u002FL, platelet ≥ 100 × 10\\^9\u002FL. Blood transfusion and growth factors must not be used within 14 days prior to screening to meet the above requirements.\n* Coagulation function: international normalized ratio or activated partial thromboplastin time ≤ 1.5× upper limit of normal range (ULN).\n* Cardiopulmonary function: left ventricular ejection fraction ≥ 50% on echocardiography; for lung function, dyspnea ≤Grade 1 of the NCI-CTCAE version 5.0 standards when breathing room air, and pulse oximetry ≥ 92%.\n* Liver function: alanine aminotransferase ≤ 1.5 × ULN, aspartate aminotransferase ≤ 1.5 × ULN, total bilirubin ≤ 1.5 × ULN (total bilirubin at least ≤ 3.0 mg\u002FdL in patients with Gilbert syndrome).\n* Renal function: creatinine clearance (by Cockcroft-Gault formula) ≥ 50 mL\u002Fmin.\n* Criteria for SLE：\n\n  1. Meet the 2019 European Alliance of Associations for Rheumatology\u002FAmerican College of Rheumatology (EULAR\u002FACR) classification criteria for SLE;\n  2. SLEDAI-2000 score \\> 6 in the moderate to severe active phase of the disease;\n  3. And have at least one British Isles Lupus Assessment Group (BILAG-2004) grade A (severe manifestation) or two grade B (moderate manifestation) organ scores, or both.\n  4. Ineffective conventional treatment or relapse of disease activity after remission. Definition of routine treatment: Use of glucocorticoids (Above 1 mg\u002Fkg\u002Fd) and cyclophosphamide, and any of the following immunomodulatory drugs for more than 6 months: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics such as rituximab, belimumab, and telitacicept.\n* Criteria for Sjögren's syndrome:\n\n  1. Meet the 2002 AECG criteria for primary Sjögren's syndrome or the 2016 ACR\u002FEULAR classification criteria;\n  2. Disease activity ESSDAI ≥ 6;\n  3. Anti-SSA\u002FRo antibody positive;\n  4. Definition of relapse\u002Frefractory: disease activity that is ineffective to conventional treatment for more than 6 months or recurs after response. Definition of conventional treatment is use of glucocorticoids and cyclophosphamide, and any of the following immunomodulatory drugs: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics including rituximab, belimumab, and telitacicept.\n* Criteria for systemic sclerosis:\n\n  1. Meet the 2013 ACR classification criteria for systemic sclerosis and meet diffuse manifestations;\n  2. Combined interstitial pneumonia: interstitial changes with ground-glass exudate detected by chest high-resolution computed tomography (HRCT);\n\n     Needs to be met c. or d.:\n  3. Ineffective conventional treatment or relapse of disease activity after remission. Definition of routine treatment: Use of glucocorticoids (Above 0.5 mg\u002Fkg\u002Fd) and cyclophosphamide, and any of the following immunomodulatory drugs for more than 6 months: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics such as rituximab and belimumab.\n  4. Meet the definition of progression: 1) Definition of skin progression: mRSS increases b \\> 25%; 2) Definition of lung disease progression: FVC decreased by 10%, or FVC decreased by 5% and DLCO decreased by 15%.\n* Criteria for inflammatory myopathy:\n\n  1. The classification criteria for inflammatory myopathy comply with the 2017 EULAR\u002FACR (including DM, PM, ASS and NM);\n  2. For patients with muscle involvement, the MMT-8 score is less than 142 and abnormalities are found in at least two of the following five core measures (PhGA, PtGA, or extramuscular disease activity score ≥ 2 points; total HAQ score ≥ 0.25; muscle enzyme level is 1.5 times upper limit of normal);\n  3. Myositis antibody positive;\n\n     Needs to be met d. or e.:\n  4. Definition of relapse\u002Frefractory: Failure of conventional treatment or relapse of disease activity after response. Definition of conventional treatment: Use of glucocorticoids (greater than 1 mg\u002Fkg\u002Fd) and cyclophosphamide, and any of the following immunomodulatory drugs for more than 6 months: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics such as rituximab and belimumab.\n  5. Meet the definition of progression: Interstitial pneumonia progresses rapidly over a short period of time.\n* Criteria for ANCA-associated vasculitis:\n\n  1. Meet the diagnostic criteria for ANCA-associated vasculitis in the 2022 ACR\u002FEULAR, including microscopic polyangiitis, granulomatous polyangiitis, eosinophilic granulomatosis with polyangiitis;\n  2. ANCA-related antibody positive (MPO-ANCA or PR3-ANCA positive);\n  3. Birmingham Vasculitis Activity Scale (BVAS) ≥ 15 points (out of a total of 63 points), indicating activity of vasculitis;\n  4. Must have at least one major item, at least three minor items, or at least two renal items, hematuria and proteinuria, in the BVAS assessment;\n  5. Definition of relapse\u002Frefractory: Failure of conventional treatment or relapse of disease activity after response. Definition of conventional treatment: Use of glucocorticoids (greater than 1 mg\u002Fkg\u002Fd) and cyclophosphamide, and any of the following immunomodulatory drugs for more than 6 months: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics such as rituximab and belimumab.\n\nExclusion Criteria:\n\n* Prohibited medications and treatments:\n\n  * Any RNA-LNP products or other LNP drugs received within the past two years.\n  * Received intravenous gamma immunoglobulin within 24 weeks prior to screening.\n  * Received plasmapheresis therapy within 12 weeks prior to screening.\n  * Subjects who have not fully recovered from surgery within 4 weeks prior to screening.\n  * Epilepsy or use of psychotropic or sedative drugs during the screening period (except medications for sleeping).\n  * Received any live or live attenuated vaccine within 12 weeks prior to screening, or requiring vaccination at any time during clinical trial treatment.\n  * Participated in clinical trial of other drugs or medical devices within 12 weeks prior to screening (except for those whose screening failed).\n* Concomitant diseases or clinical condition:\n\n  * History of lupus nephropathy requiring hemodialysis or treatment with high-dose corticosteroids (\\> 100 mg\u002Fd prednisone or equivalent) within 90 days prior to baseline.\n  * Epilepsy or use of psychotropic or sedative drugs during the screening period (except medications for sleeping).\n  * Received any live or live attenuated vaccine within 12 weeks prior to screening, or requiring vaccination at any time during clinical trial treatment.\n  * Participated in clinical trial of other drugs or medical devices within 12 weeks prior to screening (except for screen failures).\n  * Have active central nervous system lupus, including meningitis aseptic, cerebral vasculitis, demyelinating syndrome, myelopathy, acute demented, psychosis, acute inflammatory demyelinating polyradiculoneuropathy, mononeuropathy (single\u002Fmultiple), cranial neuropathy, plexopathy, status epilepticus or cerebellar ataxia.\n  * Presence of other systemic inflammations such as, but not limited to, rheumatoid arthritis, juvenile chronic arthritis, spondyloarthritis, Crohn's disease, ulcerative colitis, or psoriatic arthritis within 12 weeks prior to screening (except for those with secondary Sjögren's syndrome, who should not be excluded).\n  * Subjects who have Grade III or above congestive heart failure (NYHA grade), unstable angina or myocardial infarction, poorly controlled hypertension (hypertension is diagnosed as Grade 2 or above, risk factor stratified as high-risk, systolic blood pressure ≥ 160 mmHg and\u002For diastolic blood pressure ≥ 100 mmHg when taking one or two antihypertensive drugs, cerebrovascular accidents, or arrhythmias requiring treatment within 6 months prior to screening.\n  * Presence of active or uncontrolled infection requiring treatment; or have known or suspected ongoing, chronic, or recurrent infectious diseases (including but not limited to opportunistic infections such as pulmonary tuberculosis, atypical mycobacterosis, listeriosis or aspergillosis, HIV, hepatitis B or hepatitis C, etc.).\n  * Subjects with suspected allergy to TI-0032-III or similar drugs or a history of severe allergy or hypersensitivity reactions.\n  * History of thyrotoxicosis, including but not limited to diffuse toxic goitre, multinodular toxic goiter, thyroid autonomic high-function adenoma, and subacute thyroiditis, or thyroid color ultrasound suggests thyroid nodules TI-RADS classification as category 4 or 5.\n  * Previous history of splenectomy or loss of spleen function after splenic infarction or splenic vein thrombosis leading to direct vascular injury; or major surgery within 2 months prior to screening; or have planned surgery before the end of the trial.\n  * Have other serious\u002Fsevere acute or chronic mental illness, including recent (within the past 1 year) or current suicidal ideation or behavior; or a history of alcohol, drug, or chemical abuse within 1 year prior to screening.\n  * History of major organ transplant (e.g., heart, lung, liver, kidney) or bone marrow\u002Fhematopoietic stem cell transplantation.\n  * History of malignancy, regardless of evidence of local recurrence or metastasis and regardless of treatment; or accompanied by a history of other major diseases, such as liver disease under treatment, including but not limited to acute or chronic hepatitis, liver cirrhosis or liver failure, etc.\n  * HIV positive, or active hepatitis B virus test positive (HBsAg positive, HBV-DNA ≥ 200 copies\u002FmL is required (conversion is required if HBV-DNA is in IU\u002FmL)), or anti-HCV antibody positive and HCV-RNA positive.\n  * Women who plan to become pregnant or are pregnant or breastfeeding; or blood pregnancy test positive during screening; or unable to take effective contraceptive measures within 12 months after the last infusion of investigational drug; or planned sperm\u002Fegg donation within 12 months after the last dose of the investigational drug.\n  * Other clinically significant abnormal laboratory tests or imaging tests judged by the investigator or considered unsuitable for clinical the trial for other reasons.","ALL","18 Years","65 Years",{"count":21,"type":22},12,"ESTIMATED","INTERVENTIONAL",[25],"PHASE1","This is an open-label, dose escalation study in patients with relapsed and refractory autoimmune diseases. Study drug, TI-0032-III injection, is composed of lipid nanoparticles (LNPs) targeting T cells that encapsulate circular RNA encoding the CD19 chimeric antigen receptor (CAR), which is a therapeutic biological product. It is clinically intended for the treatment of various relapsed and refractory B cell-related autoimmune diseases, such as systemic lupus erythematosus, sjögren's syndrome, systemic sclerosis, idiopathic inflammatory myositis, and antiphospholipid syndrome.",[28,29,30,31,32],"Systemic Lupus Erythematosus (SLE)","Sjogren's Syndrome (SS)","Systemic Sclerosis (SSc)","Inflammatory Myopathy","ANCA Associated Systemic Vasculitis","RECRUITING","2026-02-09",{"date":36,"type":37},"2026-02-17","ACTUAL",{"date":39,"type":37},"2026-01-22",{"date":41,"type":22},"2027-01-30",{"name":43,"class":44},"Therorna","INDUSTRY",1,{"id":47,"slug":48,"hasResults":11,"nctId":49,"briefTitle":50,"officialTitle":51,"acronym":4,"eligibilityCriteria":52,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":53,"enrollmentInfo":54,"targetDuration":4,"studyType":23,"phases":55,"briefSummary":56,"conditions":57,"keywords":61,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":64,"lastUpdatePostDateStruct":65,"startDateStruct":67,"completionDateStruct":69,"leadSponsor":71,"locationsCount":45},"100599245","phase-1-study-of-ti-0093-injection-with-recurrentmetastatic-hpv-16-positive-solid-tumors-100599245","NCT07081984","Study of TI-0093 Injection With Recurrent\u002FMetastatic HPV-16 Positive Solid Tumors","A Phase I Clinical Study to Evaluate the Safety, Tolerability, Efficacy and Immunogenicity of TI-0093 Injection in Patients With Recurrent\u002FMetastatic HPV-16 Positive Solid Tumors","Inclusion Criteria:\n\nPatients must meet all the following inclusion criteria to be eligible for participation in this study:\n\n1. The patient provides written informed consent for the study.\n2. Willing to comply with the visit plans, treatment plans, and other requirements of the study schedule.\n3. Previous HPV16+ solid tumors.\n4. 18 to 75 years of age at the time of informed consent.\n5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 with no deterioration over the previous 2 weeks.\n6. Estimated life expectancy of more than 12 weeks.\n7. Previous HPV16 positive head and neck, cervical and other carcinoma patients with recurrent or metastatic disease, who have progressed after standard therapies, or for whom no further standard therapies are available.\n8. Patients should have at least 1 measurable lesion at baseline according to the definition of RECISTv1.1.\n9. Absolute neutrophil count ≥ 1.5 ×10\\^9\u002FL, without the use of granulocyte colony stimulating factors such as filgrastim within 2 weeks prior to study treatment. Platelet count ≥ 100 × 10\\^9\u002FL without transfusion within 2 weeks (≤ 14 days) prior to study treatment. Hemoglobin ≥ 9 g\u002FdL without transfusion or erythropoietin within 2 weeks (≤ 14 days) prior to study treatment.\n10. Aspartate transaminase and alanine aminotransferase ≤ 3 × upper limit of normal (ULN) (patients with liver metastasis \\\u003C 5 × ULN), and total bilirubin ≤ 1.5 × ULN (patients with Gilbert's Syndrome ≤ 3 × ULN).\n11. Adequate renal function defined by either a creatinine clearance ≥ 45 mL\u002Fmin (by Cockcroft-Gault formula) or serum creatinine \\\u003C 1.5 × ULN.\n12. Prothrombin time ≤ 1.5 × ULN; activated partial thromboplastin time ≤ 1.5 × ULN; international normalized ratio ≤ 1.5 × ULN.\n13. Left ventricular ejection fraction ≥ 50% measured by echocardiogram.\n14. Females of childbearing potential and males whose partners are of childbearing potential agree to the use effective contraception from signing informed consent form to 90 days after the last dose of TI-0093 injection. The test results of HCG of females with childbearing potential should be negative within 7 days prior to the first dose of TI-0093 injection.\n\nExclusion Criteria:\n\nPatients who meet any of the following exclusion criteria cannot be enrolled:\n\n1. History of any therapeutic HPV vaccination. History of any live viral vaccine or attenuated live vaccine therapies within 4 weeks prior to the first dose of TI-0093 injection.\n2. History of life-threatening hypersensitivity or known to be allergic to any ingredients contained in the TI-0093 injection.\n3. Females who are pregnant or breastfeeding. Patients who plan to donate sperm or eggs from signing informed consent form to 90 days post the last dose of TI-0093 injection.\n4. Patients with underlying comorbidity will be excluded:\n\n   A. Active known second malignancy, except for any of the following: basal cell carcinoma, squamous cell skin cancer, in situ cervical cancer and non-muscle invasive bladder cancer, which were recovered from adequate clinical treatment, and other cancers treated by surgery alone whose disease-free survival were 5 years and above.\n\n   B. Meningeal metastases, spinal cord compression or symptomatic brain metastases within 28 days prior to the first dose of TI-0093 injection (except for patients with prior brain metastases who were treated and clinically stable for 4 weeks without corticosteroid or antiepileptic drug treatment).\n\n   C. History of severe pneumonia such as interstitial lung disease within 6 months prior to the first dose of TI-0093 injection.\n\n   D. Major surgery within 4 weeks prior to the first dose of TI-0093 injection. E. Deep vein thrombosis or arterial embolism such as pulmonary embolism within 6 months prior to the first dose of TI-0093 injection.\n\n   F. Active bleeding symptoms or diseases such as active hemoptysis, gastrointestinal bleeding and hemorrhagic gastric ulcer within 28 days prior to the first dose of TI-0093 injection.\n\n   G. Alcohol dependence (averagely more than 2 units of alcohol per day (1 unit = 360 ml of beer, 45 ml of 40% liquor, or 150 ml of wine) which may affect safety assessment judged by the investigator. Drug abuse but unable to quit or mental disorders.\n\n   H. Patients with active autoimmune disease or symptoms that required systemic use of pharmacologic dose of corticosteroid and\u002For immunosuppressant within 4 weeks prior to the first dose of TI-0093 injection. Exceptions are patients with vitiligo, resolved asthma\u002Fatopy, and type 1 diabetes mellitus or hypothyroidism that can be managed by replacement therapy.\n\n   I. Severe or uncontrolled systemic diseases above:\n   1. Grade 2 and above myocardial infarction, grade 2 and above myocardial ischemia, or grade 2 and above heart failure based on New York Heart Association (NYHA) classification within 6 months prior to the first dose of TI-0093 injection. Arrhythmia such as QTc ≥ 480ms needs to be treated and uncontrolled hypertension during the screening period.\n   2. Any active or uncontrolled infection such as uncontrolled diabetes (defined as HbA1c ≥ 7.5%), asthma, clinically active diverticulitis, abdominal abscess or gastrointestinal obstruction during the screening period.\n   3. Active hepatitis B (both hepatitis B virus surface antigen being positive and hepatitis B virus carriers with a viral load \\> 200 IU\u002Fml), active hepatitis C (both HCV antibody and RNA testing being positive), positive for treponema pallidum in serum or active tuberculosis during the screening period.\n   4. Known positive test results for human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS). Prior organ allograft transplantations or allogeneic peripheral blood stem cell (PBSC) or bone marrow (BM) transplantation.\n   5. History of gastrointestinal perforation, gastrointestinal fistula or female reproductive tract fistula within 6 months prior to the first dose of TI-0093 injection. Except for those recovered after treatment judged by the investigator.\n   6. Pleural effusion, ascites or pericardial effusion requires puncture aspiration or drainage within 2 weeks prior to the enrollment.\n5. Grade 3 and above immune-related AEs or any immune-related AE lead to discontinuation of prior immunotherapy.\n6. Any previous AE has not been improved to Grade 1 and below (except for patients with hair loss, grade 2 peripheral neurotoxicity, stable hypothyroidism after hormone replacement therapy or other AEs with no safety risk judged by the investigator).\n7. Asplenia or insufficiency of spleen function caused by infarct of spleen or thrombosis of splenic vein.\n8. Systemic treatment with corticosteroids (≥ 10 mg\u002Fday prednisone or equivalent) or other immunosuppressive medications within 14 days prior to the first dose of TI-0093 injection.\n9. Washout period for any previous immunomodulatory drugs such as thymosin, interleukin-2, and interferon: last treatment is within 4 weeks prior to prior to the first dose of TI-0093 injection.\n10. Washout period for any previous anticancer therapy prior to the first dose of TI-0093 injection:\n\n    1. Last treatment is within 4 weeks for chemotherapy, biologic therapy, target therapy or immunotherapy.\n    2. Last treatment is within 2 weeks for radiotherapy, endocrine therapy or oral fluorouracil drugs.\n    3. Last treatment is within 7 days for anticancer Chinese medicine.\n    4. Last treatment is within 6 weeks for nitrosoureas and mitomycin.\n11. Last treatment with investigational product is within 5 half-lives or 4 weeks (which is longer).\n12. Any other disease or clinically significant abnormality in laboratory parameters, which in the judgment of the investigator might compromise the safety of the patient or integrity of the study, interfere with the patient participation in the trial or compromise the trial objectives.","75 Years",{"count":21,"type":22},[25],"This is a phase I, open-label, dose escalation study to assess the safety, tolerability, efficacy and immunogenicity of TI-0093 injection in patients with recurrent or metastatic HPV-16 positive solid tumors.\n\nThe primary objectives of the study are to assess safety and tolerability of TI-0093 injection in patients with recurrent or metastatic solid tumors, and to determine the maximum tolerated doses (MTDs) and recommended Phase 2 doses (RP2Ds) of TI-0093 injection.",[58,59,60],"HPV 16+ Recurrent or Metastatic Cancer","HNSCC","Cervical Cancer",[62,63],"Therapeutic tumor vaccine","Circular RNA","2025-11-21",{"date":66,"type":37},"2025-11-24",{"date":68,"type":37},"2025-11-11",{"date":70,"type":22},"2027-07-31",{"name":43,"class":44},""]