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Tests treatment safety and results for Transthyretin Amyloidosis Polyneuropathy
Official title 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)
ClinicalTrials.gov ID: NCT06539208
What this study is testing
What is YOLT-201?
YOLT-201 is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for transthyretin amyloidosis polyneuropathy.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- 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).
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 to 80
You may be able to join if
- 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);
You likely can't join if
- 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...
- 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...
See the full eligibility criteria
Who can 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 people with Gilbert syndrome, TBIL ≤ 2 times ULN;
- 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...
- 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: people 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...
- Agree to stop drinking alcohol within the screening period to 28 days after administration;
- Female people need to be menopausal (absence of menstruation for at least 1 year) or have undergone uterine/ovarian resection surgery; Male people and their partners have no fertility plans from the screening period to...
- 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.
What rules you out
- 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...
- 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...
- 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...
- 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.).
The study team makes the final eligibility decision.
Where it's taking place
- Beijing, Beijing Municipality, China
- Changsha, Hunan, China
- Hanzhou, Zhejiang, China
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years to 80 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Beijing, Beijing Municipality, China; Changsha, Hunan, China; Hanzhou, Zhejiang, China. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.