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Transthyretin Amyloidosis PolyneuropathyPhase 1/2NCT06539208

A Phase I/IIa，Open-label, Single Ascending Dose and Dose-expansion Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of YOLT-201 in Patients With Transthyretin Amyloidosis Polyneuropathy (ATTR-PN) or Transthyretin Amyloidosis Cardiomyopathy (ATTR-CM)

A Phase 1/2 study testing YOLT-201 in people with Transthyretin Amyloidosis Polyneuropathy and Transthyrexin Amyloidosis Cardiomyopathy, run by YolTech Therapeutics Co., Ltd at 3 sites in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This study will be conducted to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of YOLT-201 in participants with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) and participants with hereditary transthyretin amyloidosis with cardiomyopathy (ATTRv-CM). Read more about this study

Who is it for?
Ages 18 to 80 years
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
31 participants
Where
3 sitesChina
Study dates
23 May 2024to 30 Jun 2026
Phase
Phase 1/2
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 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age 18 - 80 years old (including the critical values), regardless of gender;
  • Body weight at the time of screening is between 40 - 90kg (including the critical values);
  • TTR gene mutation is confirmed by genetic testing;
  • At the time of screening, the following laboratory standards must be met:
  • AST, ALT, and TBIL ≤ the upper limit of the normal value (ULN);
  • For subjects with Gilbert syndrome, TBIL ≤ 2 times ULN;
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  • Glomerular filtration rate (GFR) ≥ 45 mL/min/1.73m2 (calculated according to the CKD-EPI formula);
  • Platelet count ≥ 100 × 109/L;
  • Partial thromboplastin time (APTT), prothrombin time (PT), and thrombin generation time (TGT) are all within the reference value range, fibrinogen (FIB) ≥ the lower limit of the normal value (LLN) and ≤ 1.5*ULN, the international normalized ratio (INR) ≤ ULN, and if taking anticoagulant drugs, it is ≤ 2.5*ULN;
  • Vitamin A and vitamin B12 ≥ the lower limit of the reference value (LLN);
  • Low-density lipoprotein cholesterol (LDL) < 200 mg/dL (5.17 mmol/L).
  • Drugs approved for the treatment of ATTR are not accessible (Criterion A) and/or the disease still progresses despite the use of drugs approved for the treatment of ATTR (Criterion B):
  • Criterion A: Meeting one or more of the following criteria:
  • Drugs for the treatment of ATTR are not marketed in China;
  • Unable to receive the approved drugs for ATTR treatment (e.g., intolerance or other medical, cost and/or other reasons);
  • Criterion B: Subjects have received ATTR drug treatment for at least 3 months, but the subject's condition has progressed as assessed by the investigator, and meets any of the following criteria:
  • ATTR-CM: a. Increased number of hospitalizations related to heart failure; b. Worsening of NYHA classification; c. Decrease in KCCQ score by at least 5 points; d. Decrease in 6-MWT by at least 30m; e. Increase in NT-proBNP by 30%; f. Increase in Troponin I by 30%; g. Echocardiography indicates an increase in left ventricular wall thickness by 2mm; h. Echocardiography indicates a decrease in left ventricular ejection fraction by ≥ 5% or a decrease in global longitudinal strain by ≥ 1% or a decrease in stroke volume by ≥ 5%; i. New conduction block appears; ATTR-PN: a. PND score increase by ≥ 1 point; b. FAP increases by 1 stage; c. NIS score increase by ≥ 5 points; d. NIS-Lower Limb score increase by ≥ 5 points; e. mBMI decrease by ≥ 25 kg/m2×g/L; f. 10-MWT decrease by ≥ 0.1 m/s; g. Electroneurophysiological examination (electromyography) worsens compared to the previous.
  • Agree to stop drinking alcohol within the screening period to 28 days after administration;
  • Female subjects need to be menopausal (absence of menstruation for at least 1 year) or have undergone uterine/ovarian resection surgery; Male subjects and their partners have no fertility plans from the screening period to 6 months after the end of the trial and agree to take effective non-pharmaceutical contraceptive measures during the trial;
  • The subject himself/herself (or his/her legally recognized representative) understands and signs the informed consent form;
  • Agree not to receive other ATTR drug intervention treatment within at least 8 weeks after administration of YOLT-201;
  • For ATTR-PN only:
  • Diagnosed as ATTR-PN according to the "Consensus on the Diagnosis and Treatment of Transthyretin Amyloidosis Polyneuropathy", and the NIS score at the screening is ≥ 5 and ≤ 130, and the PND score is ≤ IIIb;
  • NT-proBNP < 600pg/ml at the screening;
  • For ATTR-CM only:
  • Diagnosed as ATTR-CM according to the "Expert Consensus on the Diagnosis and Treatment of Transthyretin Cardiac Amyloidosis";
  • The New York Heart Association (NYHA) cardiac function classification is grade II - III;
  • The 6-minute walk test (6-MWT) is ≥ 150 m at the screening;
  • NT-proBNP is ≥ 600pg/mL and ≤ 3000pg/mL at the screening;
  • At the screening, echocardiography suggests evidence of cardiac involvement: the thickness of the interventricular septum and/or the posterior wall of the left ventricle is ≥ 12 mm.

Who cannot join

  • Amyloidosis is not caused by TTR protein, such as light chain amyloidosis;
  • There is meningeal transthyretin amyloidosis;
  • Allergic to any lipid nanoparticle (LNP) component or has previously received LNP and experienced treatment-related laboratory abnormalities or adverse events;
  • Use any of the following ATTR treatments within the prescribed time:
  • In the dose escalation stage of the first stage, the use history of Patisiran, Inotersen, and Vutrisiran is excluded;
  • In the dose expansion stage of the second stage, the following are excluded: Patisiran is used within 90 days before the administration of the investigational drug; Inotersen is used within 160 days before the administration of the investigational drug; Vutrisiran has a previous use history;
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  • Tafamidis: used within 10 days before the administration of the investigational drug;
  • Diflunisal: used within 3 days before the administration of the investigational drug;
  • Doxycycline and/or taurodeoxycholic acid: used within 14 days before the administration of the investigational drug;
  • Previous use history of investigational gene editing drugs;
  • Other drugs for the treatment of ATTR: the last use is less than 30 days or 5 half-lives before the administration of the investigational drug, whichever is longer.
  • Unable or unwilling to supplement vitamin A during the trial;
  • History of multiple myeloma;
  • Ophthalmological examination results at the screening are consistent with vitamin A deficiency;
  • Abnormal thyroid function test with clinical significance judged by the investigator;
  • Known or suspected systemic infection (viral, parasitic or fungal infection) within 14 days before screening;
  • History of past hepatitis B virus, hepatitis C virus, acquired immunodeficiency syndrome or positive HBsAg, HCV-Ab, and HIV-Ab at the screening;
  • History of previous liver, heart or other organ transplantation or bone marrow transplantation or expected transplantation within 1 year (except for the history of corneal transplantation or planned corneal transplantation);
  • History of bleeding or coagulation disorders (such as cirrhosis, malignant hematological disease, antiphospholipid antibody syndrome);
  • History of acute thrombosis within 6 months before screening (such as acute myocardial infarction, acute cerebral infarction), or positive Leiden factor V and/or prothrombin gene test;
  • History of malignant tumor within 5 years before screening (except for basal cell carcinoma of the skin, radicalized squamous cell carcinoma of the skin, and carcinoma in situ of the cervix);
  • Planned invasive cardiovascular surgery during the trial (such as coronary artery stent/coronary artery bypass, pacemaker placement, etc.); those who have undergone cardiovascular invasive surgery within 90 days before screening or have been hospitalized due to heart failure;
  • History of alcohol abuse within 3 years before screening (definition of alcohol abuse: women drink ≥ 4 glasses/day or 8 glasses/week, men ≥ 5 glasses or 15 glasses/week, where 1 glass = 14g of pure alcohol);
  • Expected survival period is less than 1 year;
  • Other situations that the investigator deems inappropriate to enter this trial;
  • For ATTR-PN only:
  • Other known diseases that cause motor or sensory neuropathy (such as diabetic neuropathy, neuropathy related to autoimmune diseases, etc.);
  • Diagnosed with type 1 diabetes or type 2 diabetes for ≥ 5 years;
  • NYHA cardiac function classification is grade III or IV within 90 days before screening;
  • For ATTR-CM only:
  • NYHA cardiac function classification is grade IV within 90 days before screening;
  • PND score is grade IIIa, IIIb or IV at the screening;
  • Suffering from other cardiomyopathies not caused by TTR (such as hypertensive cardiomyopathy, valvular heart disease, cardiomyopathy caused by ischemic heart disease, etc.).

Trial locations and contacts

3 sites in 1 country.

China3 sites, 3 recruiting

  • Peking Union Medical College Hospital

    Beijing, Beijing Municipality, 100000

    Shuyang Zhang, 69155068 ext. 010, shuyangzhang103@163.com

    Recruiting

  • The Second Xiangya Hospital of Central South University

    Changsha, Hunan, 410000

    Daoquan Peng, 85295407 ext. 0731, pengdq@hotmail.com

    Recruiting

  • The First Affiliated Hospital, School of Medicine, Zhejiang University

    Hanzhou, Zhejiang, 310000

    Tingbo Liang, 87236560 ext. 0571, liangtingbo@zju.edu.cn

    Recruiting

Other trials in China

About this study

This study will be conducted to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of YOLT-201 in participants with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) and participants with hereditary transthyretin amyloidosis with cardiomyopathy (ATTRv-CM).

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

Study groups in NCT06539208
Study groupRoleWhat they receive
YOLT-201ExperimentalNot described
Receives: Drug: YOLT-201

What is being measured

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

  1. Safety and Tolerability

    Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)

    Measured: through week 104

Timeline

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

  1. First posted6 Aug 2024
  2. Study start23 May 2024
  3. Primary completion30 Jun 2025 (estimated)
  4. Study completion30 Jun 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
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
31 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06539208
Sponsor's protocol ID
YT-YOLT-201-101
Status last verified
Aug 2024
First submitted
1 Aug 2024
Last updated
6 Aug 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing YOLT-201 in people with Transthyretin Amyloidosis Polyneuropathy and Transthyrexin Amyloidosis Cardiomyopathy, run by YolTech Therapeutics Co., Ltd at 3 sites 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 30 inclusion and 33 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 6 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and Tolerability (time frame: through week 104). 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 NCT06539208.

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 6 Aug 2024.

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