Hemoglobinopathies (Transfusion-dependent β-thalassemia and Sickle Cell Disease)Early Phase 1NCT07190001
YOLT-204 in Patients With Hemoglobinopathies
A Early Phase 1 study testing YOLT-204 in people with Hemoglobinopathies (Transfusion-dependent β-thalassemia and Sickle Cell Disease), run by Guangzhou Women and Children's Medical Center at 1 site in China.
Trial 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). Read more about this study
- Who is it for?
- Ages 3 to 17 years
- Conditions the study is for
- Hemoglobinopathies (Transfusion-dependent β-thalassemia and Sickle Cell Disease)
- What is being tested?
- YOLT-204
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteChina
- Study dates
- 30 Sep 2025to 30 Apr 2027
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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).
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Guangzhou women and children's medical center
Guangzhou, Guangdong, 510405
Jiang hua, +8613533330985, jiang_hua18@sina.cn
About this study
Official title: An Exploratory Clinical Study to Evaluate the Safety and Efficacy of YOLT-204 in Patients With Hemoglobinopathies (β-thalassemia and Sickle-cell Disease)
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.
- Being tested
- YOLT-204
- Medical subject headings
- Hemoglobinopathies, Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
YOLT-204Drug
The intervention group will receive YOLT-204 on day0
| Study group | Role | What they receive |
|---|---|---|
| Arms | Experimental | The intervention group will receive YOLT-204 on day0 Receives: Drug: YOLT-204 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse event rate
Calculate the rate of various adverse events
Measured: 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.
Measured: 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.
Measured: From baseline to 52 weeks after dose
Secondary outcomes (11)
The proportion of alleles with intended modifications
The proportion of alleles with intended modifications in peripheral blood leukocytes and bone marrow cells
Measured: From baseline to 52 weeks after dose
Concentration of Hemoglobin
The concentration of Hemoglobin was measured by laboratory
Measured: From baseline to 52 weeks after dose
Concentration of Fetal hemoglobin
The concentration of Fetal hemoglobin was measured by laboratory
Measured: From baseline to 52 weeks after dose
Concentration of proportion of F cell
The proportion of F cell was measured by laboratory
Measured: From baseline to 52 weeks 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.
Measured: From baseline to 52 weeks after dose
6 months of sustained transfusion reduction
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.
Measured: From baseline to 52 weeks after dose
6 months of transfusion independence
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.
Measured: From baseline to 52 weeks after dose
Free of hospitalization due to vaso-occlusive crisis
Analysis begins one month after treatment with YOLT-204, and the proportion of patients who remained free of hospitalization due to vaso-occlusive crisis.
Measured: From baseline to 52 weeks after dose
Free of any vaso-occlusive crisis
Analysis begins one month after treatment with YOLT-204, and the proportion of patients who remained free of any vaso-occlusive crisis
Measured: From baseline to 52 weeks after dose
Change of red-blood-cell transfusions given
Analysis begins one month after treatment with YOLT-204, and the Change from baseline in volume of red-blood-cell transfusions given for SCD-related indications
Measured: From baseline to 52 weeks after dose
The number of vaso-occlusive crises
Change from baseline in the number of vaso-occlusive crises within 1 year after YOLT-204 treatment.
Measured: From baseline to 52 weeks after dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2025
- Study start30 Sep 2025 (estimated)
- Primary completion30 Apr 2027 (estimated)
- Study completion30 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hemoglobinopathies (Transfusion-dependent β-thalassemia and Sickle Cell Disease)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Guangzhou Women and Children's Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07190001
- Sponsor's protocol ID
- YOLT-204-IIT-002
- Status last verified
- Sep 2025
- First submitted
- 16 Sep 2025
- Last updated
- 24 Sep 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Clinical Study to Evaluate the Safety and Efficacy of YOLT-204 in Patients With Hemoglobinopathies (β-thalassemia and Sickle-cell Disease)
- ClinicalTrials.gov ID
- NCT07190001
- Acronym / sponsor ID
- YOLT-204-IIT-002
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Guangzhou Women and Children's Medical CenterUniversity, hospital or other
- Study start
- 30 Sep 2025 (estimated)
- Primary completion
- 30 Apr 2027 (estimated)
- Study completion
- 30 Apr 2027 (estimated)
- First posted
- 24 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arms | Experimental | Drug: YOLT-204The intervention group will receive YOLT-204 on day0 |
Who may qualify
- Ages
- 3 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (18 listed)
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| YOLT-204The intervention group will receive YOLT-204 on day0 | Drug | Arms |
Primary outcome
Adverse event rate
Time frame: From baseline to 52 weeks after dose
Calculate the rate of various adverse events
3 months of sustained transfusion reduction
Time frame: From baseline to 52 weeks 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 sustained HbF level ≥20%
Time frame: From baseline to 52 weeks after dose
Proportion of patients who, starting one month after YOLT-204 treatment and without concomitant hydroxyurea, maintain HbF ≥ 20 % for at least three consecutive months.
11 secondary outcomes
The proportion of alleles with intended modifications
Time frame: From baseline to 52 weeks after dose
Concentration of Hemoglobin
Time frame: From baseline to 52 weeks after dose
Concentration of Fetal hemoglobin
Time frame: From baseline to 52 weeks after dose
Concentration of proportion of F cell
Time frame: From baseline to 52 weeks after dose
3 months of transfusion independence
Time frame: From baseline to 52 weeks after dose
6 months of sustained transfusion reduction
Time frame: From baseline to 52 weeks after dose
6 months of transfusion independence
Time frame: From baseline to 52 weeks after dose
Free of hospitalization due to vaso-occlusive crisis
Time frame: From baseline to 52 weeks after dose
Free of any vaso-occlusive crisis
Time frame: From baseline to 52 weeks after dose
Change of red-blood-cell transfusions given
Time frame: From baseline to 52 weeks after dose
The number of vaso-occlusive crises
Time frame: From baseline to 52 weeks after dose
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing YOLT-204 in people with Hemoglobinopathies (Transfusion-dependent β-thalassemia and Sickle Cell Disease), run by Guangzhou Women and Children's Medical Center at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 24 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jiang Hua (+8613533330985, jiang_hua18@sina.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse event rate (time frame: From baseline to 52 weeks after dose). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2025.