Status:
NOT_YET_RECRUITING
YOLT-204 in Patients With Hemoglobinopathies
Lead Sponsor:
Guangzhou Women and Children's Medical Center
Conditions:
Hemoglobinopathies (Transfusion-dependent β-thalassemia and Sickle Cell Disease)
Eligibility:
All Genders
3-17 years
Phase:
EARLY_PHASE1
Brief Summary
This is a single-arm, open-label, single-dose, dose-escalation trial that plans to enrol 3-18 patients with transfusion-dependent β-thalassaemia (TDT) or sickle-cell disease (SCD). Its primary aims ar...
Eligibility Criteria
Inclusion
- 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.
Exclusion
- History of multiple drug allergies or hypersensitivity to oligonucleotides or lipid nanoparticles (LNP).
- Clinically significant active bacterial, viral, fungal, or parasitic infection at screening, as judged by the investigator.
- White blood cell (WBC) count \< 3 × 10⁹/L and/or platelet count \< 100 × 10⁹/L at screening.
- 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.
- Serum ferritin ≥ 5 000 ng/mL, or MRI T2\* evidence of severe cardiac or hepatic iron overload.
- Positive for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus antibody, anti-HIV antibody, or specific anti-Treponema pallidum antibody.
- Prior hematopoietic stem-cell transplantation, gene therapy, or gene-editing therapy.
- Participation in another clinical trial and receipt of investigational product within 3 months before first dose of study drug.
- Current or prior malignancy, myeloproliferative disorder, or immunodeficiency disease.
- Severe psychiatric illness precluding cooperation; clinically significant pulmonary hypertension requiring medical intervention; recent malaria; first-degree relative with hematologic malignancy.
- Positive pregnancy test, pregnancy, or lactation in female subjects at screening.
- Any condition (past or present) that, in the investigator's opinion, could confound results, compromise participation, or render the patient unsuitable for the study.
- Use within 3 months before study drug: erythropoietin (EPO), thalidomide, hydroxyurea, luspatercept, or similar agents.
- In subjects ≥ 12 years, abnormal transcranial Doppler (TCD) with middle cerebral or internal carotid artery velocity ≥ 200 cm/s.
- History of moyamoya disease or imaging findings consistent with moyamoya at screening, assessed by the investigator as conferring bleeding risk.
Key Trial Info
Start Date :
September 30 2025
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
April 30 2027
Estimated Enrollment :
18 Patients enrolled
Trial Details
Trial ID
NCT07190001
Start Date
September 30 2025
End Date
April 30 2027
Last Update
September 24 2025
Active Locations (1)
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1
Guangzhou women and children's medical center
Guangzhou, Guangdong, China, 510405