YOLT-204 in Patients With Hemoglobinopathies

NCT07190001 | Not Yet Recruiting Early Phase 1

• 1 other identifier: YOLT-204-IIT-002
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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 are to evaluate the safety and tolerability of a single administration of YOLT-204 and to obtain preliminary data on its effect on plasma fetal-haemoglobin levels. The main-study screening period may last up to 60 days; the treatment day is Day 0 (D0). Safety follow-up continues through Week 52 post-dose. After completion of the main study, participants will enter long-term follow-up extending to 15 years post-dose.

Conditions

Hemoglobinopathies (Transfusion-dependent β-thalassemia and Sickle Cell Disease)

Outcome Measures

Primary Outcomes (3)

• Adverse event rate

  Calculate the rate of various adverse events

  From baseline to 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.

  From baseline to 52 weeks after dose

• 3 months of sustained HbF level ≥20%

  Proportion of patients who, starting one month after YOLT-204 treatment and without concomitant hydroxyurea, maintain HbF ≥ 20 % for at least three consecutive months.

  From baseline to 52 weeks after dose

Secondary Outcomes (11)

• The proportion of alleles with intended modifications

  From baseline to 52 weeks after dose

• Concentration of Hemoglobin

  From baseline to 52 weeks after dose

• Concentration of Fetal hemoglobin

  From baseline to 52 weeks after dose

• Concentration of proportion of F cell

  From baseline to 52 weeks after dose

• 3 months of transfusion independence

  From baseline to 52 weeks after dose

Study Arms (1)

Arms

EXPERIMENTAL

The intervention group will receive YOLT-204 on day0

Drug: YOLT-204

Interventions

YOLT-204 DRUG

The intervention group will receive YOLT-204 on day0

Arms

Eligibility Criteria

• Age: 3 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• Guangzhou Women and Children's Medical Center: lead

Study Sites (1)

Guangzhou women and children's medical center

Guangzhou, Guangdong, 510405, China

Location

MeSH Terms

Conditions

Hemoglobinopathies; Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia

Central Study Contacts

Jiang Hua

CONTACT

+8613533330985; jiang_hua18@sina.cn

Gong Wei Wei

CONTACT

+8615336388770; sdgongww@163.com

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: September 16, 2025
• First Posted: September 24, 2025
• Study Start: September 30, 2025
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2027
• Last Updated: September 24, 2025

Record last verified: 2025-09

Locations

CN (1)