Familial HypercholesterolemiaEarly Phase 1NCT06461702
Clinical Exploration Trial of YOLT-101 in the Treatment of Familial Hypercholesterolemia (FH)
A Early Phase 1 study testing YOLT-101 in people with Familial Hypercholesterolemia, run by The First Affiliated Hospital of Bengbu Medical University at 1 site in China.
Trial summary
This study is a single arm, open, single dose escalation trial aimed at evaluating the safety and tolerability of YOLT-101 administration in patients with familial hypercholesterolemia; Determination of YOLT-101 OBD; Preliminary evaluation of the effects of single administration of YOLT-101 on plasma lipid and… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Familial Hypercholesterolemia
- What is being tested?
- YOLT-101
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteChina
- Study dates
- 1 Apr 2024to Dec 2025
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men or women aged ≥ 18 years and ≤ 65 years (including boundary values) who signed informed consent.
- Meets the diagnostic criteria for familial hypercholesterolemia. When screening, there are mutations in the PCSK9 and/or ApoB and/or LDLR genes.
- 4. When screening, the weight should be ≥ 40kg, and the body mass index (BMI) should be between 18-30 kg/m2 (including boundary values).
- 5. During screening, subjects must meet the following laboratory standards: 5.1 Blood routine: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count (PLT) ≥ 100 × 109/L, hemoglobin count (HGB) ≥ 90 g/dL; 5.2 Liver function: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) < 2.0 × ULN, total bilirubin (TBIL) ≤ 1.5 × ULN; 5.3 Renal function: Serum creatinine (Cr) ≤ 1.5 × ULN, and glomerular filtration rate (GFR)>60mL/min 1.73m2; 5.4 Coagulation function: prothrombin time (PT), activated partial thromboplastin time (APTT), international standardized ratio (INR)<1.5 x ULN; 5.5 Low density lipoprotein cholesterol (LDL-C) ≥ 4.21mmol/L, and fasting triglycerides<5.6mmol/L.
- 6. The subjects and their partners must take effective contraceptive measures during the participation in this study until 6 months after the end of the main study.
- 7. The subject must agree not to accept other lipid-lowering drugs for at least 28 days after receiving the investigational drug.
- 8. Voluntarily sign informed consent.
Who cannot join
- Those who have used any prescription drugs that affect blood lipid metabolism within at least 14 days before receiving the study drug (or within 7 half lives of the drug, whichever is longer, applicable to small molecule/small nuclear acid drugs) or within 3 months (applicable to biological agents such as PCSK9 inhibitors), or who have used any over-the-counter drugs that affect blood lipid metabolism within at least 14 days before receiving the study drug (such as Chinese medicine/traditional Chinese patent medicines and simple preparations, vitamins, fish oil (>1000mg/day), drugs containing red koji rice or health products, etc.), (Exception of those who have received stable non-cyclical hormone replacement therapy for more than 8 weeks and agree not to change the hormone treatment more than 28 days after the study drug administration); individuals who have participated in clinical studies of other lipid-lowering drugs and have accepted the investigational drugs within 6 months before the screening period.
- Poorly controlled hypertensive patients who have receive conventional treatments (systolic blood pressure (SBP) ≥ 160mmHg and/or diastolic blood pressure (DBP) ≥ 100mmHg).
- Poorly controlled diabetes patients (glycosylated hemoglobin>8.5%).
- Individuals who are allergic to drugs or mRNA vaccine components contained in lipid nanoparticles (LNPs), or have experienced adverse reactions to LNP drug therapy, such as:
- 4.1 After receiving LNP drug treatment, ALT or AST>3.0 × ULN; 4.2 After receiving LNP drug treatment, INR>1.5 or APTT/d-dimer>1.5 × ULN; 4.3 Any infusion response that requires clinical intervention, slows down infusion rate, or stops LNP drugs treatment; 4.4 Any other adverse reactions that researchers believe are related to the treatment of LNP drugs.
- Within three months before the screening, individuals who smoke more than 5 cigarettes per day or consume an equal amount of nicotine or nicotine substitutes.
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- Individuals with a history of alcohol abuse [consuming more than 14 units of alcohol per week (1 unit ≈ 360mL of beer or 45mL of 40% liquor or 150mL of wine)] within 3 months before the screening; Individuals positive for alcohol breath test during the screening or admission.
- Grade III-IV heart failure defined by the New York Heart Association (NYHA), or left ventricular ejection fraction<50%, or prolonged QTc interval (>470ms in females and>450ms in males) found during the screening.
- Suffering poorly controlled severe arrhythmia , such as recurrent and highly symptomatic ventricular tachycardia with poorly drug controlled, atrial fibrillation with rapid ventricular reaction, or supraventricular tachycardia within three months before the screening.
- Myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass grafting, severe deep vein thrombosis or pulmonary embolism within three months before the screening; Cerebrovascular accidents occurring within 6 months before the screening or planning for cardiac surgery or revascularization during the main study period.
- Suffering from diseases that have a significant impact on blood lipid levels and cannot be controlled, such as nephrotic syndrome, severe liver disease, Cushing's syndrome, thyroid dysfunction, etc. (Individuals with hypothyroidism who have undergone stable thyroid replacement therapy for ≥ 28 days before screening, have normal TSH testing, and agree to maintain the dose of thyroid replacement drugs unchanged during the study can be considered to be enrolled).
- Individuals who have donated more than 500 mL of blood within three months before screening.
- Those who are unable or unwilling to accept the medication treatment required before the investigational treatment.
- Patients who underwent antithrombotic treatment (such as warfarin, dabigatran, and apixaban) within 14 days prior to enrollment.
- Those who are prone to bleeding or have a history of coagulation disorders (such as cirrhosis, malignant hematological diseases, antiphospholipid antibody syndrome);
- Patients with an expected survival period of less than 2 years.
- Individuals who are known or suspected to have systemic viral, parasitic, or fungal infections, or are expected to receive antibiotic treatment within 14 days after screening.
- Hepatitis B surface antigen (HBsAg) or hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) antibody positive during the screening.
- Individuals who have received liver, heart, or other solid organ transplantation, bone marrow transplantation within one year before the screening, or having a transplantation plan during the clinical trial.
- Individuals with a history of malignant tumors within 5 years before the screening (excluding curative skin basal cell carcinoma, skin squamous cell carcinoma, cervical carcinoma in situ, low-grade prostate carcinoma in situ, and curative thyroid basal carcinoma in situ).
- Individuals with a history of drug use within three years before the screening.
- Pregnant or lactating women.
- Patients with other systemic diseases such as the blood system, digestive system, or central nervous system (including cerebrovascular diseases and degenerative diseases) that the researchers believe will interfere with the evaluation or limit the participation in the trial.
- Severe mental diseases that researchers believe which cannot be fully controlled by the medication treatment.
- Those who are unwilling to follow the research procedures or are unwilling to fully cooperate.
- Other situations that researchers believe not suitable to participate in the clinical trial.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
The First Affiliated Hospital of Bengbu Medical College
Bengbu, Anhui, 233004
Wang Hongju, Doctor, 0552-3086026, 1649134019@qq.com
About this study
This study is a single arm, open, single dose escalation trial aimed at evaluating the safety and tolerability of YOLT-101 administration in patients with familial hypercholesterolemia; Determination of YOLT-101 OBD; Preliminary evaluation of the effects of single administration of YOLT-101 on plasma lipid and lipoprotein levels.
Note: OBD is defined as the dosage at which plasma PCSK9 protein levels decrease between 60% and 95% from baseline on the 28th day after YOLT-101 administration. OBD ≤ Maximum Tolerable Dose (MTD).
Read the detailed description
In this study, the longest screening period for the main study was 42 days, the treatment day was Day 1 (D1), and the safe follow-up period was up to 52 weeks after medication. In the main study, when OBD occurs, additional subjects will be added to the dose group (specific number of cases will be negotiated between the cooperating organization and investigators) for further validation. In addition, subjects in the first dose group can voluntarily receive a second drug administration of OBD level.
After the completion of the main study, participants will undergo long-term follow-up. According to the Technical Guidelines for Long term Follow up Clinical Research of Gene Therapy Products (Trial) released by CDE, a long-term follow-up until 15 years after the medicine administration is required .
- Conditions
- Familial Hypercholesterolemia
- Being tested
- YOLT-101
- Medical subject headings
- Hyperlipoproteinemia Type II
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
YOLT-101Drug
The IP is administered intravenously at the predetermined dose.
| Study group | Role | What they receive |
|---|---|---|
| YOLT-101 | Experimental | Not described Receives: Drug: YOLT-101 |
What is being measured
The primary outcome is the main question the study is designed to answer.
safety evaluation of YOLT-101
The safety of YOLT-101 evaluated by the proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs)
Measured: through week 52
Secondary outcomes (6)
pharmacokinetics of YOLT-101
The Peak Plasma Concentration (Cmax) of YOLT-101. 0.5 predose,0.5,1,1.5,2,4,6,8,12,24,48,72,144,312 hours
Measured: through Day 28
pharmacodynamics
The effect of YOLT-101 on serum levels of LDL-C
Measured: through week 52
pharmacodynamics
The effect of YOLT-101 on plasma levels of PCSK9
Measured: through week 52
pharmacokinetics of YOLT-101
Area under the plasma concentration versus time curve (AUC). 0.5 predose,0.5,1,1.5,2,4,6,8,12,24,48,72,144,312 hours
Measured: through Day 28
pharmacokinetics of YOLT-101
Tmax
Measured: through Day 28
pharmacokinetics of YOLT-101
T1/2
Measured: through Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2024
- Study start1 Apr 2024
- Primary completionAug 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Familial HypercholesterolemiaStudies 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
- 13 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The First Affiliated Hospital of Bengbu Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06461702
- Sponsor's protocol ID
- FH-YOLT-101-1
- Status last verified
- Apr 2024
- First submitted
- 16 Apr 2024
- Last updated
- 17 Jun 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Exploration Trial of YOLT-101 in the Treatment of Familial Hypercholesterolemia (FH)
- ClinicalTrials.gov ID
- NCT06461702
- Acronym / sponsor ID
- FH-YOLT-101-1
- Conditions
- Familial Hypercholesterolemia
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 13 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital of Bengbu Medical UniversityUniversity, hospital or other
- Study start
- 1 Apr 2024 (actual)
- Primary completion
- Aug 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 17 Jun 2024 (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 study is a single arm, open, single dose escalation trial aimed at evaluating the safety and tolerability of YOLT-101 administration in patients with familial hypercholesterolemia; Determination of YOLT-101 OBD; Preliminary evaluation of the effects of single administration of YOLT-101 on plasma lipid and lipoprotein levels.
Note: OBD is defined as the dosage at which plasma PCSK9 protein levels decrease between 60% and 95% from baseline on the 28th day after YOLT-101 administration. OBD ≤ Maximum Tolerable Dose (MTD).
Detailed description
In this study, the longest screening period for the main study was 42 days, the treatment day was Day 1 (D1), and the safe follow-up period was up to 52 weeks after medication. In the main study, when OBD occurs, additional subjects will be added to the dose group (specific number of cases will be negotiated between the cooperating organization and investigators) for further validation. In addition, subjects in the first dose group can voluntarily receive a second drug administration of OBD level.
After the completion of the main study, participants will undergo long-term follow-up. According to the Technical Guidelines for Long term Follow up Clinical Research of Gene Therapy Products (Trial) released by CDE, a long-term follow-up until 15 years after the medicine administration is required .
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| YOLT-101 | Experimental | Drug: YOLT-101 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Men or women aged ≥ 18 years and ≤ 65 years (including boundary values) who signed informed consent.
- Meets the diagnostic criteria for familial hypercholesterolemia. When screening, there are mutations in the PCSK9 and/or ApoB and/or LDLR genes.
- 4. When screening, the weight should be ≥ 40kg, and the body mass index (BMI) should be between 18-30 kg/m2 (including boundary values).
- 5. During screening, subjects must meet the following laboratory standards: 5.1 Blood routine: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count (PLT) ≥ 100 × 109/L, hemoglobin count (HGB) ≥ 90 g/dL; 5.2 Liver function: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) < 2.0 × ULN, total bilirubin (TBIL) ≤ 1.5 × ULN; 5.3 Renal function: Serum creatinine (Cr) ≤ 1.5 × ULN, and glomerular filtration rate (GFR)>60mL/min 1.73m2; 5.4 Coagulation function: prothrombin time (PT), activated partial thromboplastin time (APTT), international standardized ratio (INR)<1.5 x ULN; 5.5 Low density lipoprotein cholesterol (LDL-C) ≥ 4.21mmol/L, and fasting triglycerides<5.6mmol/L.
- 6. The subjects and their partners must take effective contraceptive measures during the participation in this study until 6 months after the end of the main study.
Key exclusion criteria (26 listed)
- Those who have used any prescription drugs that affect blood lipid metabolism within at least 14 days before receiving the study drug (or within 7 half lives of the drug, whichever is longer, applicable to small molecule/small nuclear acid drugs) or within 3 months (applicable to biological agents such as PCSK9 inhibitors), or who have used any over-the-counter drugs that affect blood lipid metabolism within at least 14 days before receiving the study drug (such as Chinese medicine/traditional Chinese patent medicines and simple preparations, vitamins, fish oil (>1000mg/day), drugs containing red koji rice or health products, etc.), (Exception of those who have received stable non-cyclical hormone replacement therapy for more than 8 weeks and agree not to change the hormone treatment more than 28 days after the study drug administration); individuals who have participated in clinical studies of other lipid-lowering drugs and have accepted the investigational drugs within 6 months before the screening period.
- Poorly controlled hypertensive patients who have receive conventional treatments (systolic blood pressure (SBP) ≥ 160mmHg and/or diastolic blood pressure (DBP) ≥ 100mmHg).
- Poorly controlled diabetes patients (glycosylated hemoglobin>8.5%).
- Individuals who are allergic to drugs or mRNA vaccine components contained in lipid nanoparticles (LNPs), or have experienced adverse reactions to LNP drug therapy, such as:
- 4.1 After receiving LNP drug treatment, ALT or AST>3.0 × ULN; 4.2 After receiving LNP drug treatment, INR>1.5 or APTT/d-dimer>1.5 × ULN; 4.3 Any infusion response that requires clinical intervention, slows down infusion rate, or stops LNP drugs treatment; 4.4 Any other adverse reactions that researchers believe are related to the treatment of LNP drugs.
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-101The IP is administered intravenously at the predetermined dose. | Drug | YOLT-101 |
Primary outcome
safety evaluation of YOLT-101
Time frame: through week 52
The safety of YOLT-101 evaluated by the proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs)
6 secondary outcomes
pharmacokinetics of YOLT-101
Time frame: through Day 28
pharmacodynamics
Time frame: through week 52
pharmacodynamics
Time frame: through week 52
pharmacokinetics of YOLT-101
Time frame: through Day 28
pharmacokinetics of YOLT-101
Time frame: through Day 28
pharmacokinetics of YOLT-101
Time frame: through Day 28
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2024.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
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-101 in people with Familial Hypercholesterolemia, run by The First Affiliated Hospital of Bengbu Medical University 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 7 inclusion and 26 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: status not confirmed, as of the sponsor's last update on 17 Jun 2024. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Wang Hongju (13955231336, 1649134019@qq.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
safety evaluation of YOLT-101 (time frame: through week 52). 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 17 Jun 2024.