A Pilot Study on the Safety and Efficacy of YOLT-204 for Transfusion-Dependent Beta-Thalassemia

Early Phase 1

Not yet recruiting

• Conditions: Transfusion Dependent Beta Thalassemia
• Interventions: Drug: YOLT-204

• Registration Number: NCT06678165
• Lead Sponsor: First Affiliated Hospital of Guangxi Medical University

Brief Summary

This study is a single-arm, open-label, dose-escalation trial, planning to enroll 3-9 patients with transfusion-dependent β-thalassemia, aimed at assessing the safety and tolerability of a single-dose of YOLT-204 in patients with transfusion-dependent β-thalassemia; to preliminarily evaluate the impact of a single -dose of YOLT-204 on the levels of fetal hemoglobin in the plasma

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-10
• Study First Submitted: 2024-10-31
• Study First Submitted QC: 2024-11-05
• Last Update Submitted: 2024-11-05
• Study First Posted: 2024-11-07
• Last Update Posted: 2024-11-07
• Study Start: 2024-12-31
• Primary Completion: 2026-06-01
• Study Completion: 2026-06-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 3

Inclusion Criteria

Not provided

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Exclusion Criteria

1. History of multiple drug allergies or a history of allergic reactions to oligonucleotides or lipid nanoparticles (LNPs).
2. Diagnosed with compound alpha-thalassemia.
3. Clinically significant active bacterial, viral, fungal, or parasitic infections at the time of screening, as judged by the investigator.
4. White blood cell count (WBC) <3×10^9/L and/or platelet count <100×10^9/L not due to hypersplenism, as judged by the investigator.
5. Uncorrected bleeding disorders.
6. Received treatment with erythropoietin (EPO) within the three months prior to enrollment.
7. Severe iron overload, with serum ferritin levels ≥5000 ng/ml.
8. Positive for hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus, antibodies to human immunodeficiency virus (HIV), or specific antibodies to Treponema pallidum (syphilis).
9. History of hematopoietic stem cell transplantation, gene therapy, or gene editing therapy.
10. Participation in another clinical study and use of investigational drugs within 3 months prior to starting the study drug.
11. History or current presence of malignant tumors or myeloproliferative diseases or immunodeficiency diseases.
12. Presence of severe mental illness that prevents cooperation with treatment; significant pulmonary arterial hypertension requiring medical intervention; recent malaria; a history of hematological tumors in immediate family members.
13. Any past or current disease, treatment, or laboratory abnormality that may interfere with the study results, affect the patient's full participation in the study, or that the investigator deems unsuitable for participation in this clinical study.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
The intervention group will receive YOLT-204 on day0	YOLT-204	-

Primary Outcome Measures

Name	Time	Method
Treatment-Emergent Adverse Events	52 weeks after dose	Number of Participants with Treatment-Emergent Adverse Events
Laboratory Test Findings	52 weeks after dose	Number of Participants with Clinically Significant Clinical Laboratory Test Findings
Safety Measurements	52 weeks after dose	Number of Participants with Clinically Significant Safety Measurements
3 months of sustained transfusion reduction	4 months after dose	Analysis begins one month after treatment with YOLT-204, and the proportion of patients who achieve at least 3 months of sustained transfusion reduction (sustained TR3) is obtained.
3 months of transfusion independence	4 months after dose	Analysis begins one month after treatment with YOLT-204, and the proportion of patients who achieve at least 3 months of transfusion independence (sustained TI3) is obtained.

Secondary Outcome Measures

Name	Time	Method
6 months of sustained transfusion reduction	7 months after dose	Analysis begins one month after treatment with YOLT-204, and the proportion of patients who achieve at least 6 months of sustained transfusion reduction (sustained TR6) is obtained.
6 months of transfusion independence	7 months after dose	Analysis begins one month after treatment with YOLT-204, and the proportion of patients who achieve at least 6 months of transfusion independence (sustained TI6) is obtained.
The proportion of alleles with intended modifications	52 weeks after dose	The proportion of alleles with intended modifications in peripheral blood leukocytes and bone marrow cells over time.
Fetal hemoglobin concentration	52 weeks after dose	The change in fetal hemoglobin concentration over time after YOLT-204 infusion
Total hemoglobin concentration	52 weeks after dose	The change in total hemoglobin concentration over time after YOLT-204 infusion.

Trial Locations

Locations (1)

The First Affiliated Hospital of Guangxi Medical University; 🇨🇳 Nanning, Guangxi, China