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

NCT06678165 | Not Yet Recruiting Early Phase 1

• 1 other identifier: YOLT-204-IIT
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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

Conditions

Transfusion Dependent Beta Thalassemia

Outcome Measures

Primary Outcomes (5)

• Treatment-Emergent Adverse Events

  Number of Participants with Treatment-Emergent Adverse Events

  52 weeks after dose

• Laboratory Test Findings

  Number of Participants with Clinically Significant Clinical Laboratory Test Findings

  52 weeks after dose

• Safety Measurements

  Number of Participants with Clinically Significant Safety Measurements

  52 weeks after dose

• 3 months of sustained transfusion reduction

  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.

  4 months after dose

• 3 months of transfusion independence

  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.

  4 months after dose

Secondary Outcomes (5)

• 6 months of sustained transfusion reduction

  7 months after dose

• 6 months of transfusion independence

  7 months after dose

• The proportion of alleles with intended modifications

  52 weeks after dose

• Fetal hemoglobin concentration

  52 weeks after dose

• Total hemoglobin concentration

  52 weeks after dose

Study Arms (1)

The intervention group will receive YOLT-204 on day0

EXPERIMENTAL

Drug: YOLT-204

Interventions

YOLT-204 DRUG

The intervention group will receive YOLT-204 on day0

The intervention group will receive YOLT-204 on day0

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age between 18 to 35 years, gender not limited.
• The patient has fully understood this study and voluntarily signed an informed consent form.
• Clinically diagnosed as a patient with transfusion-dependent β-thalassemia, excluding the genotype: β0β0.
• Karnofsky Performance Status (KPS) score of at least 70.
• Obtain detailed medical records of red blood cell transfusions within 2 years prior to the patient signing the informed consent form, including the volume or units of transfusion and the levels of red blood cells and hemoglobin before and after transfusion.
• No severe hematopoietic dysfunction, with heart, lung, liver, and kidney functions essentially normal.
• Coagulation function: International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) both ≤1.5×ULN (Upper Limit of Normal).
• Renal function: Creatinine ≤1.5×ULN, or when creatinine \>1.5×ULN, the creatinine clearance is \>50ml/min (calculated according to the Cockcroft-Gault formula).
• Liver function: Alanine Aminotransferase (ALT) ≤3×ULN and Aspartate Aminotransferase (AST) ≤3×ULN; Direct Bilirubin ≤2.5×ULN.
• Cardiac function: Left Ventricular Ejection Fraction (LVEF) ≥50%.
• Good compliance, willing to adhere to visit schedules, trial plans, laboratory tests, and other trial steps.
• Willing to participate in long-term follow-up studies.

You may not qualify if:

• History of multiple drug allergies or a history of allergic reactions to oligonucleotides or lipid nanoparticles (LNPs).
• Diagnosed with compound alpha-thalassemia.
• Clinically significant active bacterial, viral, fungal, or parasitic infections at the time of screening, as judged by the investigator.
• 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.
• Uncorrected bleeding disorders.
• Received treatment with erythropoietin (EPO) within the three months prior to enrollment.
• Severe iron overload, with serum ferritin levels ≥5000 ng/ml.
• 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).
• History of hematopoietic stem cell transplantation, gene therapy, or gene editing therapy.
• Participation in another clinical study and use of investigational drugs within 3 months prior to starting the study drug.
• History or current presence of malignant tumors or myeloproliferative diseases or immunodeficiency diseases.
• 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.
• 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.

Sponsors & Collaborators

• First Affiliated Hospital of Guangxi Medical University: lead

Study Sites (1)

The First Affiliated Hospital of Guangxi Medical University

Nanning, Guangxi, 530000, China

Location

Central Study Contacts

Rongrong Liu

CONTACT

+86 0771 5356510; liurongrong@stu.gxmu.edu.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2024
• First Posted: November 7, 2024
• Study Start: December 31, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: November 7, 2024

Record last verified: 2024-10

Locations

CN (1)