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

November 5, 2024 updated by: First Affiliated Hospital of Guangxi Medical University
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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
3

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Guangxi
      • Nanning, Guangxi, China, 530000
        • The First Affiliated Hospital of Guangxi Medical University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria：

  1. Age between 18 to 35 years, gender not limited.
  2. The patient has fully understood this study and voluntarily signed an informed consent form.
  3. Clinically diagnosed as a patient with transfusion-dependent β-thalassemia, excluding the genotype: β0β0.
  4. Karnofsky Performance Status (KPS) score of at least 70.
  5. 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.
  6. No severe hematopoietic dysfunction, with heart, lung, liver, and kidney functions essentially normal.
  7. Coagulation function: International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) both ≤1.5×ULN (Upper Limit of Normal).
  8. 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).
  9. Liver function: Alanine Aminotransferase (ALT) ≤3×ULN and Aspartate Aminotransferase (AST) ≤3×ULN; Direct Bilirubin ≤2.5×ULN.
  10. Cardiac function: Left Ventricular Ejection Fraction (LVEF) ≥50%.
  11. Good compliance, willing to adhere to visit schedules, trial plans, laboratory tests, and other trial steps.
  12. Willing to participate in long-term follow-up studies.

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: The intervention group will receive YOLT-204 on day0
Drug: YOLT-204
The intervention group will receive YOLT-204 on day0

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Treatment-Emergent Adverse Events
Time Frame: 52 weeks after dose
Number of Participants with Treatment-Emergent Adverse Events
52 weeks after dose
Laboratory Test Findings
Time Frame: 52 weeks after dose
Number of Participants with Clinically Significant Clinical Laboratory Test Findings
52 weeks after dose
Safety Measurements
Time Frame: 52 weeks after dose
Number of Participants with Clinically Significant Safety Measurements
52 weeks after dose
3 months of sustained transfusion reduction
Time Frame: 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.
4 months after dose
3 months of transfusion independence
Time Frame: 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.
4 months after dose

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
6 months of sustained transfusion reduction
Time Frame: 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.
7 months after dose
6 months of transfusion independence
Time Frame: 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.
7 months after dose
The proportion of alleles with intended modifications
Time Frame: 52 weeks after dose
The proportion of alleles with intended modifications in peripheral blood leukocytes and bone marrow cells over time.
52 weeks after dose
Fetal hemoglobin concentration
Time Frame: 52 weeks after dose
The change in fetal hemoglobin concentration over time after YOLT-204 infusion
52 weeks after dose
Total hemoglobin concentration
Time Frame: 52 weeks after dose
The change in total hemoglobin concentration over time after YOLT-204 infusion.
52 weeks after dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
First Affiliated Hospital of Guangxi Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 31, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 31, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 5, 2024

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 7, 2024

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 7, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 5, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • YOLT-204-IIT

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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