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)

Status: Recruiting
Location: See all (3) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1/Phase 2
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).

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 80
Healthy Volunteers: f
View:

• 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;

‣ 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.

Locations
Other Locations
China
Peking Union Medical College Hospital
RECRUITING
Beijing
The Second Xiangya Hospital of Central South University
RECRUITING
Changsha
The First Affiliated Hospital, School of Medicine, Zhejiang University
RECRUITING
Hanzhou
Time Frame
Start Date: 2024-05-23
Estimated Completion Date: 2026-06-30
Participants
Target number of participants: 31
Treatments
Experimental: YOLT-201
Sponsors
Leads: YolTech Therapeutics Co., Ltd

This content was sourced from clinicaltrials.gov