AzTrials
AzTrials

Transthyroxin Amyloidosis CardiomyopathyEarly Phase 1NCT06082050

Efficacy and Safety of Intravenous YOLT-201 for Transthyretin Amyloidosis Cardiomyopathy

A Early Phase 1 study testing YOLT-201 in people with Transthyroxin Amyloidosis Cardiomyopathy, run by Zhejiang University at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This study is a single-arm, open-label, single-dose escalation trial aimed at evaluating the safety and tolerability of YOLT-201 treatment in patients with Transthyretin Amyloidosis Cardiomyopathy （ATTR-CM）, as well as assessing the preliminary efficacy of subjects treated with YOLT-201. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Transthyroxin Amyloidosis Cardiomyopathy
What is being tested?
YOLT-201
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
1 siteChina
Study dates
2 Nov 2023to 10 Feb 2026
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 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female subjects aged ≥18 and ≤80 years old at the time of signing informed consent.
  • Diagnosis of transthyretin cardiac amyloidosis (ATTR-CM) based on the 2021 "Chinese Expert Consensus on the Diagnosis and Treatment of Transthyretin Cardiac Amyloidosis," the 2021 European Society of Cardiology (ESC) guidelines, and the 2023 American College of Cardiology (ACC) guidelines, including hereditary ATTR cardiac amyloidosis (ATTRv-CM) and wild-type ATTR cardiac amyloidosis (ATTRwt-CM); and relevant indicators meet the following criteria:
  • 2.1 New York Heart Association (NYHA) functional classification of I to III; 2.2 6-minute walk test (6-MWT) ≥ 150 meters at screening; 2.3 Echocardiogram evidence of cardiac involvement: left ventricular wall thickness (interventricular septum and/or posterior wall thickness ≥12 mm); 2.4 Brain natriuretic peptide N-terminal prohormone (NT-proBNP) < 2000 pg/mL at screening; 2.5 Receiving stable and standardized cardiovascular medication treatment.
  • Body weight must not be less than 40 kg at screening.
  • Subjects must meet the following laboratory criteria at screening:
  • 4.1 Aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (except for Gilbert's syndrome), International Normalized Ratio (INR) < upper limit of normal (ULN); 4.2 Subjects with a history of Gilbert's syndrome have a total bilirubin not exceeding twice the upper limit of normal (ULN) during the screening period; 4.3 Estimated glomerular filtration rate (eGFR) > 45 mL/min/1.73m^2 at screening; 4.4 Platelet count ≥ 100 × 10^9/L; 4.5 Coagulation function at screening: fibrinogen, activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) are all within the normal range; 4.6 Low-density lipoprotein (LDL) cholesterol < 200 mg/dL; 4.7 Vitamin A level ≥ lower limit of normal (LLN); 4.8 Vitamin B12 level ≥ lower limit of normal (LLN).
Show all 13Show fewer
  • Acceptance of ATTR-CM medication treatment:
  • 5.1 Unable to receive existing ATTR-CM-related medication due to regional medical resources, health policies, personal financial capacity, or drug intolerance; 5.2 Despite receiving at least 6 months of ATTR-CM medication treatment, the subject's ATTR-CM condition still progresses (meeting at least one of the following): Increased hospitalizations related to heart failure; Worsening of NYHA classification; 6-MWT decrease of at least 30 meters; NT-proBNP increase by 30%; Troponin increase by 30%; Echocardiogram indicates: increase in left ventricular wall thickness by 2 mm, or decrease in left ventricular ejection fraction by ≥5%, or decrease in global longitudinal strain by ≥1%, or decrease in stroke volume by ≥5%, or worsening diastolic function; New conduction block on electrocardiogram.
  • No intake of alcohol from the start of the screening period to 28 days after receiving the trial treatment medication.
  • Female subjects must be postmenopausal for at least one year, or have undergone hysterectomy.
  • Male subjects and their partners must use highly effective contraceptive measures recognized by the doctor throughout the trial process and for at least 5 months after the trial ends.
  • Male subjects must not donate sperm within 84 days after receiving study medication.
  • Voluntary signing of informed consent.

Who cannot join

  • Amyloidosis that is not related to TTR protein degeneration, such as immunoglobulin light chain (AL) amyloidosis.
  • History of multiple myeloma.
  • Indeterminate monoclonal gammopathy (MGUS) and/or immunoglobulin free light chain (FLC) ratio alterations, unless fat, bone marrow, or cardiac biopsy confirms the absence of light chains but presence of TTR protein through mass spectrometry or immunoelectron microscopy. For chronic kidney disease (CKD) subjects with no monoclonal protein in blood and urine, the acceptable FLC ratio is 0.26 to 2.25. If the risks of biopsy outweigh the benefits, different results may be discussed with local hematologists, investigators, and medical monitors.
  • Allergy to any lipid nanoparticle (LNP) components, or history of exposure to LNP components or laboratory abnormalities or adverse reaction events related to their treatment: 4.1 Normal baseline, ALT or AST > 3 × ULN or appearance of baseline triple value after receiving LNP product. 4.2 Normal baseline, INR, APTT, or D-dimer > 1.5 × ULN; if baseline is higher than normal after receiving LNP product, it is 1.5 times the baseline value. 4.3 Any adverse reactions related to LNP product treatment are defined as grade 3 or higher (CTCAE). Injection site reactions (IRR) requiring treatment or discontinuation of infusion; slowing down the infusion rate to alleviate infusion-related reactions. The investigator believes that any adverse reaction events related to LNP treatment should be excluded.
  • Use of any of the following ATTR treatments within a certain period:
  • 5.1 Patisiran (LNP small interfering RNA siRNA) treatment product (within 90 days after administration).
Show all 32Show fewer
  • 5.2 Previous treatment with Inotersen (antisense oligonucleotide ASO) (within 160 days after administration).
  • 5.3 Previous use of Vutrisiran (investigational siRNA therapeutic GalNAc conjugate).
  • 5.4 Tafamidis (TTR stabilizer): less than 10 days since last drug administration before study drug administration.
  • 5.5 Diflunisal (TTR stabilizer): less than 3 days since last drug administration before study drug administration.
  • 5.6 Doxycycline and/or tauroursodeoxycholic acid (TTR chaperone): less than 14 days since last drug administration before study drug administration.
  • 5.7 Any other drugs used for the treatment of ATTR-CM: less than 30 days or 5 half-lives (whichever is longer) since last drug administration before study drug administration.
  • Other organic heart diseases, such as ischemic heart disease, uncontrolled hypertension, valvular heart disease, etc., leading to cardiomyopathy.
  • Current or previous NYHA class IV symptoms or worsening heart failure symptoms within 90 days before or during screening.
  • Hospitalization or invasive surgery due to cardiovascular and cerebrovascular diseases within 90 days before or during screening. For example, acute coronary syndrome, unstable angina, stroke, TIA, coronary artery reconstruction, cardiac device implantation, valvular repair, or major surgery, etc.
  • Expected to undergo invasive cardiovascular surgery (such as coronary artery stent, pacemaker implantation, etc.) within 28 days after medication.
  • Subjects who cannot or are unwilling to supplement vitamin A.
  • Subjects who cannot or are unwilling to accept the required medication treatment plan before treatment.
  • Antiplatelet (such as aspirin, clopidogrel) or antithrombotic treatment (such as warfarin, dabigatran, apixaban) within 14 days before study drug administration.
  • History of bleeding diathesis or coagulation disorders (such as liver cirrhosis, malignant hematological diseases, antiphospholipid antibody syndrome).
  • The investigator believes that the expected survival is less than 2 years.
  • Ophthalmological examination results consistent with vitamin A deficiency.
  • Known or suspected systemic viral, parasitic, or fungal infections, or expected to receive antibiotic treatment for bacterial infections within 14 days after screening.
  • History of hepatitis B or C infection or positive for hepatitis B surface antigen (HBsAg) or hepatitis C virus antibody (HCV Ab) at screening.
  • History of human immunodeficiency virus (HIV) positivity.
  • Clinically significant thyroid function abnormalities judged by the investigator.
  • History of liver, heart, or other solid organ transplantation or bone marrow transplantation within 1 year at screening, or expected transplantation. Note: No history or plan for corneal transplantation.
  • History of active malignant tumors within 5 years before screening, except for basal cell carcinoma of the skin, cured squamous cell carcinoma of the skin, cured cervical cancer, or low-grade prostate cancer under observation.
  • History of alcohol abuse or drug abuse within 3 years before screening.
  • Female subjects with childbearing potential or who are breastfeeding.
  • Other physical, social, or psychological diseases, including the use of illicit drugs or alcohol, which the investigator believes may adversely affect the subject's safety, impair the assessment of study results, or prevent the subject from complying with any conditions of this study, laboratory abnormalities, or other reasons.
  • Unwilling to comply with study procedures, including follow-ups as specified in the protocol, or unwilling to cooperate fully with the investigator.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Qi Zhang, M.D. contact

13858108798

qi.zhang@zju.edu.cn

China1 site, 1 recruiting

  • the First Affiliated Hospital, Zhejiang University School of Medicine

    Hangzhou, Zhejiang, 310009

    Tingbo Liang, MD, PHD, 086-571-87236688, liangtingbo@zju.edu.cn

    Recruiting

Other trials in China

About this study

This study is a single-arm, open-label, single-dose escalation trial aimed at evaluating the safety and tolerability of YOLT-201 treatment in patients with Transthyretin Amyloidosis Cardiomyopathy （ATTR-CM）, as well as assessing the preliminary efficacy of subjects treated with YOLT-201.

Being tested
YOLT-201

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • YOLT-201Drug

    Infusion of YOLT-201 at Day 1， Subjects may voluntarily accept the second study drug treatment at the OBD (Optimal Biological Dose) level.

Study groups in NCT06082050
Study groupRoleWhat they receive
YOLT-201ExperimentalInfusion of YOLT-201 at Day 1， Subjects may voluntarily accept the second study drug treatment at the OBD (Optimal Biological Dose) level.
Receives: Drug: YOLT-201

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Adverse event Adverse event Adverse events

    Adverse events

    Measured: hrough study completion, an average of 1 year

Secondary outcomes (44)

  1. Cmax

    Cmax

    Measured: hrough study completion, an average of 1 year

  2. Tmax

    Tmax

    Measured: hrough study completion, an average of 1 year

  3. AUCinf

    AUCinf

    Measured: through study completion, an average of 1 year

  4. AUClast

    AUClast

    Measured: through study completion, an average of 1 year

  5. t1/2

    t1/2

    Measured: through study completion, an average of 1 year

  6. CL/F

    CL/F

    Measured: through study completion, an average of 1 year

  7. change of TTR

    change of TTR

    Measured: through study completion, an average of 1 year

  8. change of QOL-DN

    change of QOL-DN

    Measured: Week3,Week24,Week52

  9. change of EQ-5D-5L

    change of EQ-5D-5L

    Measured: Week 24、Week 52

  10. change of 10-MWT

    change of 10-MWT

    Measured: Week 24、Week 52

  11. change of NFL

    change of NFL

    Measured: Week 3、Week 24、Week 52

  12. change of mBMI

    change of mBMI

    Measured: Week 3、Week 24、Week 52

  13. change of NT-proBNP

    NT-proBNP

    Measured: Week 24、Week 36、Week 52

  14. change of troponin

    change of troponin

    Measured: Week 24、Week 36、Week 52

  15. change of 6-MWT

    change of 6-MWT

    Measured: Week 36、Week 52

  16. change of NYHA cardiac function classification change of NYHA cardiac function classification

    change of NYHA cardiac function classification NYHA cardiac function classification change of NYHA cardiac function classification

    Measured: Week 24、Week 36、Week 52

  17. change of KCCQ

    change of KCCQ

    Measured: Week 24、Week 36、Week 52

  18. change of Interventricular septal wall thickness

    change of Interventricular septal wall thickness on echocardiography

    Measured: Week 52

  19. change of Left ventricular (LV) posterior wall thickness

    change of Left ventricular (LV) posterior wall thickness on echocardiography

    Measured: Week 52

  20. change of LV mass

    change of LV mass on echocardiography

    Measured: Week 52

  21. change of LV end-diastolic volume

    change of LV end-diastolic volume on echocardiography

    Measured: Week 52

  22. change of LV end-systolic volume

    change of LV end-systolic volume on echocardiography

    Measured: Week 52

  23. change of LV ejection fraction

    change of LV ejection fraction on echocardiography

    Measured: Week 52

  24. change of Cardiac output

    change of Cardiac output on echocardiography

    Measured: Week 52

  25. change of Global longitudinal strain

    change of Global longitudinal strain on echocardiography

    Measured: Week 52

  26. change of Left atrial size

    change of Left atrial size on echocardiography

    Measured: Week 52

  27. change of Left ventricular end-diastolic volume on Cardiac magnetic resonance

    change of Left ventricular end-diastolic volume on Cardiac magnetic resonance

    Measured: W52

  28. change of Left ventricular end-systolic volume on Cardiac magnetic resonance

    change of Left ventricular end-systolic volume on Cardiac magnetic resonance

    Measured: Week 52

  29. change of Left ventricular systolic volume on Cardiac magnetic resonance

    change of Left ventricular systolic volume on Cardiac magnetic resonance

    Measured: Week 52

  30. change of Left ventricular ejection fraction on Cardiac magnetic resonance

    change of Left ventricular ejection fraction on Cardiac magnetic resonance

    Measured: Week 52

  31. change of Overall longitudinal strain of left ventricle on Cardiac magnetic resonance

    change of Overall longitudinal strain of left ventricle on Cardiac magnetic resonance

    Measured: Week 52

  32. change of Mitral ring plane contraction displacement on Cardiac magnetic resonance

    change of Mitral ring plane contraction displacement on Cardiac magnetic resonance

    Measured: Week 52

  33. change of Left ventricular myocardial mass on Cardiac magnetic resonance

    change of Left ventricular myocardial mass on Cardiac magnetic resonance

    Measured: Week 52

  34. change of Right ventricular end-diastolic volume on Cardiac magnetic resonance

    change of Right ventricular end-diastolic volume on Cardiac magnetic resonance

    Measured: Week 52

  35. change of Right ventricular end-systolic volume on Cardiac magnetic resonance

    change of Right ventricular end-systolic volume on Cardiac magnetic resonance

    Measured: Week 52

  36. change of Right ventricular systolic volume on Cardiac magnetic resonance

    change of Right ventricular systolic volume on Cardiac magnetic resonance

    Measured: Week 52

  37. change of Right ventricular ejection fraction on Cardiac magnetic resonance

    change of Right ventricular ejection fraction on Cardiac magnetic resonance

    Measured: Week 52

  38. change of Tricuspid ring plane contraction offset on Cardiac magnetic resonance

    change of Tricuspid ring plane contraction offset on Cardiac magnetic resonance

    Measured: Week 52

  39. change of Right ventricular longitudinal strain on Cardiac magnetic resonance

    change of Right ventricular longitudinal strain on Cardiac magnetic resonance

    Measured: Week 52

  40. change of Left atrial volume on Cardiac magnetic resonance

    change of Left atrial volume on Cardiac magnetic resonance

    Measured: Week 52

  41. change of Right atrial volume on Cardiac magnetic resonance

    change of Right atrial volume on Cardiac magnetic resonance

    Measured: Week 52

  42. change of Extracellular volume on Cardiac magnetic resonance

    change of Extracellular volume on Cardiac magnetic resonance

    Measured: Week 52

  43. level of anti-drug antibody

    level of anti-drug antibody

    Measured: through study completion, an average of 1 year

  44. level of cas9 antibody

    level of cas9 antibody

    Measured: through study completion, an average of 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Oct 2023
  2. Study start2 Nov 2023
  3. Primary completion3 Jul 2025 (estimated)
  4. Study completion10 Feb 2026 (estimated)

Resources

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
7 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06082050
Sponsor's protocol ID
YOLT-201_2023_IIT_01
Status last verified
Nov 2024
First submitted
19 Sep 2023
Last updated
14 Feb 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing YOLT-201 in people with Transthyroxin Amyloidosis Cardiomyopathy, run by Zhejiang 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 13 inclusion and 32 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: looking for participants now, as of the sponsor's last update on 14 Feb 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 Qi Zhang, M.D. (13858108798, qi.zhang@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse event Adverse event Adverse events (time frame: hrough study completion, an average of 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06082050.

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 14 Feb 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in