YOLT-204 in Patients With Hemoglobinopathies

Ki vehet részt

• Aged 3-17 years (inclusive); any sex
• The subject and/or his/her legally authorized guardian/representative must fully understand the study and voluntarily sign a written informed-consent form
• Karnofsky Performance Status (KPS) ≥ 70 (if ≥ 16 years old) or Lansky Performance Scale (LPS) ≥ 70 (if < 16 years old)
• Detailed medical records of red-cell transfusions during the 2 years before informed-consent signature must be available, including volume or units transfused and pre-/post-transfusion red-cell and hemoglobin levels
• No severe hematopoietic dysfunction; cardiac, pulmonary, hepatic, and renal function essentially normal
• Coagulation: international normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × upper limit of normal (ULN)
• Renal function: serum creatinine ≤ 1.5 × ULN; if creatinine > 1.5 × ULN, calculated creatinine clearance > 50 mL/min by the Schwartz formula
• Hepatic function: alanine aminotransferase (ALT) ≤ 3 × ULN and aspartate aminotransferase (AST) ≤ 3 × ULN
• Cardiac function: left-ventricular ejection fraction (LVEF) ≥ 50 %
• Good compliance; willing to adhere to visit schedules, study procedures, laboratory tests, and other protocol requirements
• Agrees to use at least one highly effective contraceptive method from informed-consent signature through the end of the main study (Week 52 visit)
• Willing to participate in long-term follow-up
• Screening genotype shows HbSS or HbSβ0; prior reports acceptable if assessed as adequate by the investigator
• If on L-glutamine, regimen must have been stable for ≥ 3 months before study-drug administration; if on hydroxyurea, must have discontinued ≥ 8 weeks before study-drug administration
• Meets severe SCD criteria: despite optimal supportive therapy (including, but not limited to, analgesics and hydroxyurea), at least two of the following events occurred in the 12 months before screening:
• Severe intermittent acute pain requiring healthcare-provider management
• Acute chest syndrome with new pulmonary infiltrate on chest imaging plus pneumonia-like symptoms, pain, or fever
• Splenic sequestration crisis manifested by enlarged spleen, left upper-quadrant pain, and acute Hb drop > 20 g/L

Ki nem vehet részt

• 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 < 3 × 10⁹/L and/or platelet count < 100 × 10⁹/L at screening; 4.Uncorrected bleeding diathesis. 5.Massive splenomegaly at screening (spleen edge below the umbilicus or > 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