YOLT-204 in Patients With Hemoglobinopathies

NCT ID: NCT07190001

Last Updated: 2025-09-24

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-30
• Study Completion Date: 2027-04-30

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)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arms

The intervention group will receive YOLT-204 on day0

Group Type: EXPERIMENTAL

YOLT-204

Intervention Type: DRUG

The intervention group will receive YOLT-204 on day0

Interventions

YOLT-204

The intervention group will receive YOLT-204 on day0

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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 Criteria

• 1.History of multiple drug allergies or hypersensitivity to oligonucleotides or lipid nanoparticles (LNP).

2.Clinically significant active bacterial, viral, fungal, or parasitic infection at screening, as judged by the investigator.

3.White blood cell (WBC) count < 3 × 10⁹/L and/or platelet count < 100 × 10⁹/L at screening.

4.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.

6.Serum ferritin ≥ 5 000 ng/mL, or MRI T2* evidence of severe cardiac or hepatic iron overload.

7.Positive for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus antibody, anti-HIV antibody, or specific anti-Treponema pallidum antibody.

8.Prior hematopoietic stem-cell transplantation, gene therapy, or gene-editing therapy.

9.Participation in another clinical trial and receipt of investigational product within 3 months before first dose of study drug.

10.Current or prior malignancy, myeloproliferative disorder, or immunodeficiency disease.

11.Severe psychiatric illness precluding cooperation; clinically significant pulmonary hypertension requiring medical intervention; recent malaria; first-degree relative with hematologic malignancy.

12.Positive pregnancy test, pregnancy, or lactation in female subjects at screening.

13.Any condition (past or present) that, in the investigator's opinion, could confound results, compromise participation, or render the patient unsuitable for the study.

14.Use within 3 months before study drug: erythropoietin (EPO), thalidomide, hydroxyurea, luspatercept, or similar agents.

15.In subjects ≥ 12 years, abnormal transcranial Doppler (TCD) with middle cerebral or internal carotid artery velocity ≥ 200 cm/s.

16.History of moyamoya disease or imaging findings consistent with moyamoya at screening, assessed by the investigator as conferring bleeding risk.

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Guangzhou Women and Children's Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Guangzhou women and children's medical center

Guangzhou, Guangdong, China

Countries

China

Central Contacts

Jiang Hua

Role: CONTACT

jiang_hua18@sina.cn

+8613533330985

Gong Wei Wei

Role: CONTACT

sdgongww@163.com

+8615336388770

Facility Contacts

Jiang hua

Role: primary

jiang_hua18@sina.cn

+8613533330985

Other Identifiers

YOLT-204-IIT-002

Identifier Type: -

Identifier Source: org_study_id