Hemoglobinopathies (Transfusion-dependent ß-thalassemia and Sickle cell disease)
Conditions
Interventions
1.0 mg/kg:YOLT-204 Injection at 1.0 mg/kg
0.6 mg/kg:YOLT-204 Injection at 0.6 mg/kg
1.25 mg/kg:YOLT-204 Injection at 1.25 mg/kg
TBD group (Sample size to be determined):YOLT-206 Injection Therapy (dose: to be decided)
Sponsors
Guangzhou Women and Children's Medical Center,Guangzhou Medical University
Eligibility
Sex/Gender
All
Age
3 Years to 17 Years
Inclusion criteria
Inclusion criteria: 1. Age 3 to 17 years (inclusive of boundary values), either gender. 2. The subject and/or their legal guardian/representative have fully understood the study and voluntarily signed the written informed consent form. 3. KPS score >=70 (for age >=16 years) or LPS score >=70 (for age 1.5×ULN, endogenous creatinine clearance >50 mL/min (calculated using the Schwartz formula). 8. Liver function: Alanine aminotransferase (ALT) =50%. 10. Good compliance, willing to adhere to visit schedules, study protocols, laboratory tests, and other study procedures. 11. Subject agrees to use at least one highly effective contraceptive method from the time of signed informed consent until the end of the main study (Week 52 visit). 12. Willing to participate in long-term follow-up studies. 13. Screening genetic testing shows HbSS or HbSß0 genotype; previously obtained test reports are acceptable upon investigator assessment. 14. If the subject is using L-glutamine, the dosing regimen must be stable for at least 3 months prior to administration of the study drug; if the subject is using hydroxyurea, it must be discontinued for at least 8 weeks prior to administration of the study drug. 15. Meet criteria for severe SCD: Despite standard supportive care (including but not limited to analgesia and hydroxyurea), at least two of the following events occurred within the 1 year prior to screening: (1) Severe intermittent acute pain requiring medical intervention; (2) Acute chest syndrome, with new pulmonary infiltrates on chest imaging accompanied by pneumonia-like symptoms, pain, or fever; (3) Splenic sequestration crisis, characterized by splenomegaly, left upper quadrant pain, and acute decrease in Hb level >20 g/L.
Exclusion criteria
Exclusion criteria: 1.History of multiple drug allergies or hypersensitivity to oligonucleotides or lipid nanoparticles (LNP). 2.Clinically significant active bacterial, viral, fungal, or parasitic infection at screening, as judged by the investigator. 3.White blood cell (WBC) count 4 cm below the costal margin) deemed by the investigator to preclude enrollment. 6.Serum ferritin >= 5 000 ng/mL, or MRI T2* evidence of severe cardiac or hepatic iron overload. 7.Positive for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus antibody, anti-HIV antibody, or specific anti-Treponema pallidum antibody. 8.Prior hematopoietic stem-cell transplantation, gene therapy, or gene-editing therapy. 9.Participation in another clinical trial and receipt of investigational product within 3 months before first dose of study drug. 10.Current or prior malignancy, myeloproliferative disorder, or immunodeficiency disease. 11.Severe psychiatric illness precluding cooperation; clinically significant pulmonary hypertension requiring medical intervention; recent malaria; first-degree relative with hematologic malignancy. 12.Positive pregnancy test, pregnancy, or lactation in female subjects at screening. 13.Any condition (past or present) that, in the investigator’s opinion, could confound results, compromise participation, or render the patient unsuitable for the study. 14.Use within 3 months before study drug: erythropoietin (EPO), thalidomide, hydroxyurea, luspatercept, or similar agents. 15.In subjects >= 12 years, abnormal transcranial Doppler (TCD) with middle cerebral or internal carotid artery velocity >= 200 cm/s. 16.History of moyamoya disease or imaging findings consistent with moyamoya at screening, assessed by the investigator as conferring bleeding risk.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse event rate;HbF level >=20% sustained for at least 3 months;The proportion of patients with a continuous reduction in blood transfusion for at least 3 months; | — |
Secondary
| Measure | Time frame |
|---|---|
| Fetal hemoglobin concentration;The ratio of intentionally modified alleles in the bone marrow cells;Proportion of subjects who remained free of any vaso-occlusive crisis;The proportion of patients who achieved transfusion independence for at least 6 months;The proportion of patients who achieved transfusion independence for at least 3 months;Proportion of subjects who remained free of hospitalization due to vaso-occlusive crisis;The ratio of intentionally modified alleles in the peripheral blood leukocytes;Change from baseline in volume of red-blood-cell transfusions given for SCD-related indications;Change from baseline in the number of vaso-occlusive crises;Hemoglobin concentration;proportion of F cell;The proportion of patients with a continuous reduction in blood transfusion for at least 6 months; | — |
Countries
China
Contacts
Public ContactZhou Wenhao
Guangzhou Women and Children's Medical Center,Guangzhou Medical University
Outcome results
None listed