Clinical Trials List
Protocol NumberALN-TTRSC04-004
NCT Number(ClinicalTrials.gov Identfier)NCT07223203
Active
2025-10-01 - 2031-04-30
Phase III
Recruiting3
ICD-10G63
Polyneuropathy in diseases classified elsewhere
ICD-10G65.0
Sequelae of Guillain-Barre syndrome
ICD-10G65.1
Sequelae of other inflammatory polyneuropathy
ICD-10G65.2
Sequelae of toxic polyneuropathy
ICD-9357.4
Polyneuropathy in other diseases classified elsewhere
TRITON-PN: A phase 3, global, randomized, open-label trial evaluating the efficacy and safety of nucresiran in patients with hereditary transthyretin transporter amyloid polyneuropathy (hATTR-PN).
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Sponsor
Aylaren Corporation
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Trial scale
Multi-Regional Multi-Center
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Update
2026/07/13
Investigators and Locations
Co-Principal Investigator
- Kon-Ping Lin Division of Neurology
- Wen-Chung Yu Division of Cardiovascular Diseases
- Yi-Chu Liao Division of Neurology
- 賴冠霖 Division of Neurology
- 蕭丞宗 Division of Neurology
- 季康揚 Division of Neurology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- YEN-HUNG LIN Division of Cardiovascular Diseases
- SHIN-JOE YEH Division of Neurology
- SUNG-TSANG HSIEH Division of Neurology
- Ming-Jen Lee Division of Neurology
- HSUEH-WEN HSUEH Division of Neurology
- 林昭文 Division of Ophthalmology
- 江樸田 Division of Neurology
- 薛頌儒 Division of Neurology
The Actual Total Number of Participants Enrolled
0 Recruiting
Principal Investigator
Long-Sun Ro
Co-Principal Investigator
- Hong-Chou Kuo Division of Neurology
- 洪國竣 Division of Cardiovascular Diseases
- 張國軒 Division of Neurology
- 廖洺鋒 Division of Neurology
- 謝珮甄 Division of Neurology
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Patients with hereditary transthyretin transporter amyloid polyneuropathy (hATTR-PN)
Objectives
Primary Objectives
• To confirm the efficacy of nucresiran in patients with hATTR-PN by assessing its effect on neurological function impairment.
Secondary Objectives
To evaluate the efficacy of nucresiran compared to placebo in the following areas:
• To confirm the efficacy of nucresiran on quality of life, neurological function impairment, nutritional status, disability, and gait speed.
• To demonstrate the superiority of nucresiran over vutrisiran in serum transthyretin transporter (TTR) concentrations.
Exploratory Objectives
• To confirm the efficacy of nucresiran on neurological function impairment, quality of life, disability, autonomic dysfunction, and neurobiological markers.
• To describe changes in echocardiographic and other cardiac angiographic parameters, as well as cardiac biomarkers, in patients treated with nucresiran.
• To describe the pharmacodynamic (PD) effects of nucresiran on serum TTR and vitamin A concentrations.
• To describe the plasma pharmacokinetics (PK) of nucresiran.
• To assess whether nucresiran-resistant antibodies (ADA) develop.
Safety Objectives
• To confirm the efficacy of nucresiran for... Safety and tolerability of hATTR-PN patients
Test Drug
Nucresiran (ALN-TTRSC04)
vutrisiran (ALN-TTRSC02)
vutrisiran (ALN-TTRSC02)
Active Ingredient
Nucresiran (ALN-TTRSC04)
VUTRISIRAN
VUTRISIRAN
Dosage Form
Pre-filled injections
Pre-filled injections
Pre-filled injections
Dosage
300 mg/1.5mL
25 mg/0.5mL
25 mg/0.5mL
Endpoints
• Compared to the placebo group in the APOLLO trial, the change from baseline in the modified neurological impairment scale score +7 (mNIS+7) at month 9.
Inclution Criteria
Patients are eligible for inclusion in this trial if they meet all of the following criteria:
Age and Sex
1. Male or female aged 18 years (or the legal age of consent) to 85 years (inclusive) at the time of initial signing of the participant consent form.
Patient and Disease Characteristics
2. Diagnosed with hATTR amyloidosis with polyneuropathy and a history of TTR gene mutation.
3. Neuropathic Impairment Score (NIS) between 5 and 130 (inclusive; this criterion must be met at the second follow-up visit at the baseline period).
4. Polyneuropathy Disability (PND) score ≤ 3b (this criterion must be met at the second follow-up visit at the baseline period).
5. Karnofsky Performance Status (KPS) score ≥ 60%.
Informed Consent
6. The patient understands, is willing, and is able to comply with the trial requirements and provides written informed consent.
Age and Sex
1. Male or female aged 18 years (or the legal age of consent) to 85 years (inclusive) at the time of initial signing of the participant consent form.
Patient and Disease Characteristics
2. Diagnosed with hATTR amyloidosis with polyneuropathy and a history of TTR gene mutation.
3. Neuropathic Impairment Score (NIS) between 5 and 130 (inclusive; this criterion must be met at the second follow-up visit at the baseline period).
4. Polyneuropathy Disability (PND) score ≤ 3b (this criterion must be met at the second follow-up visit at the baseline period).
5. Karnofsky Performance Status (KPS) score ≥ 60%.
Informed Consent
6. The patient understands, is willing, and is able to comply with the trial requirements and provides written informed consent.
Exclusion Criteria
Patients are ineligible to participate in the trial if they meet any of the following criteria:
Disease-Specific Conditions
1. Have undergone a liver transplant, or the administrator believes a liver transplant is likely to be performed during the treatment period of this trial.
2. Have a known history of another (non-hATTR) form of amyloidosis, or clinical evidence of leptomeningeal amyloidosis.
3. New York Heart Association (NYHA) Heart Failure Class II > 2
Laboratory Evaluation
4. At screening, any laboratory parameter assessment meets the following criteria:
a. Alanine transaminase (ALT) or aspartate transaminase (AST) > 2.5 × Upper Limit of Normal (ULN).
b. Total bilirubin > 1.5 × ULN (> 2 × ULN for patients with Gilbert's syndrome).
c. International Normalized Ratio (INR) > 2.0 (INR ≤ 3.5 is permissible for patients receiving anticoagulant therapy). 5. Platelet count < 50,000/μL
6. Absolute neutrophil count < 1500 cells/mm³
7. Estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73m² (to be calculated using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula)
8. Vitamin B12 concentration below the lower limit of normal
9. Known HIV infection; or evidence of acute or chronic hepatitis C or hepatitis B virus infection
Previous/Concomitant Therapies
10. Previously received or currently receiving TTR-lowering therapy (e.g., patisiran, vutrisiran, inotersen, eplontersen, or gene therapy targeting TTR)
11. Currently using tafamidis, acoramidis, doxycycline, or tauroursodeoxycholic acid; if any of these drugs have been previously used, 14 days must be completed before administration (Day 1) 12. Currently receiving diflunisal; if previously used, a 3-day washout must be completed before administration (Day 1).
13. Expected to begin approved TTR stabilization therapy (e.g., tafamidis or acoramidis) within the first 18 months after randomization.
14. Previously received anti-TTR antibody therapy (i.e., "TTR depletion agent").
15. Received investigational drug within the past 30 days (or 5 half-lives of the investigational drug, whichever is longer), or is currently involved in follow-up to another clinical trial. Any drug authorized by a local or regional health authority (including emergency use) is not considered an investigational drug.
Medical Conditions
16. Presence of other known causes of sensorimotor or autonomic neuropathy (e.g., autoimmune diseases, monogammaglobulinemia) that a treating physician believes will lead to neuropathy.
17. Acute coronary syndrome within the past 3 months. 18. Uncontrolled and clinically significant arrhythmia or unstable angina.
19. Known type 1 diabetes.
20. Type 2 diabetes for ≥ 5 years.
21. Untreated hypothyroidism or hyperthyroidism.
22. Underwent major surgery within the past 3 months, or has a planned major surgery during the trial period up to month 18.
23. Has an active infection requiring systemic antiviral, antiparasitic, or antimicrobial therapy, and will not complete treatment before administration (day 1).
24. Has other medical conditions or comorbidities (e.g., malignancy, neuropsychiatric disorders, etc.) deemed by the administrator to potentially interfere with trial compliance or data interpretation.
25. History of multiple drug allergies, or a history of allergic reactions to any component or excipient of the investigational drug.
26. History of intolerance to subcutaneous (SC) injection.
27. Life expectancy < 2 years according to the administrator's clinical judgment. Contraception, Pregnancy, and Breastfeeding
28. Unwilling to adhere to contraceptive requirements during the trial.
29. Pregnant or breastfeeding female patients.
Use of Alcohol and Illegal Substances
30. Unwilling or unable to restrict alcohol consumption throughout the trial.
Exclude individuals with daily alcohol intake > 2 units during the trial (unit: 1 glass of wine [approx. 125 mL] = 1 serving of spirits [approx. 1 fluid ounce (29.574 mL)] = ½ pint of beer [approx. 284 mL]).
31. History of alcohol use disorder within the 12 months immediately preceding screening, as determined by the administrator.
32. Use of illegal substances within the past 5 years, which the administrator deems would interfere with adherence to trial procedures or follow-up visits.
Disease-Specific Conditions
1. Have undergone a liver transplant, or the administrator believes a liver transplant is likely to be performed during the treatment period of this trial.
2. Have a known history of another (non-hATTR) form of amyloidosis, or clinical evidence of leptomeningeal amyloidosis.
3. New York Heart Association (NYHA) Heart Failure Class II > 2
Laboratory Evaluation
4. At screening, any laboratory parameter assessment meets the following criteria:
a. Alanine transaminase (ALT) or aspartate transaminase (AST) > 2.5 × Upper Limit of Normal (ULN).
b. Total bilirubin > 1.5 × ULN (> 2 × ULN for patients with Gilbert's syndrome).
c. International Normalized Ratio (INR) > 2.0 (INR ≤ 3.5 is permissible for patients receiving anticoagulant therapy). 5. Platelet count < 50,000/μL
6. Absolute neutrophil count < 1500 cells/mm³
7. Estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73m² (to be calculated using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula)
8. Vitamin B12 concentration below the lower limit of normal
9. Known HIV infection; or evidence of acute or chronic hepatitis C or hepatitis B virus infection
Previous/Concomitant Therapies
10. Previously received or currently receiving TTR-lowering therapy (e.g., patisiran, vutrisiran, inotersen, eplontersen, or gene therapy targeting TTR)
11. Currently using tafamidis, acoramidis, doxycycline, or tauroursodeoxycholic acid; if any of these drugs have been previously used, 14 days must be completed before administration (Day 1) 12. Currently receiving diflunisal; if previously used, a 3-day washout must be completed before administration (Day 1).
13. Expected to begin approved TTR stabilization therapy (e.g., tafamidis or acoramidis) within the first 18 months after randomization.
14. Previously received anti-TTR antibody therapy (i.e., "TTR depletion agent").
15. Received investigational drug within the past 30 days (or 5 half-lives of the investigational drug, whichever is longer), or is currently involved in follow-up to another clinical trial. Any drug authorized by a local or regional health authority (including emergency use) is not considered an investigational drug.
Medical Conditions
16. Presence of other known causes of sensorimotor or autonomic neuropathy (e.g., autoimmune diseases, monogammaglobulinemia) that a treating physician believes will lead to neuropathy.
17. Acute coronary syndrome within the past 3 months. 18. Uncontrolled and clinically significant arrhythmia or unstable angina.
19. Known type 1 diabetes.
20. Type 2 diabetes for ≥ 5 years.
21. Untreated hypothyroidism or hyperthyroidism.
22. Underwent major surgery within the past 3 months, or has a planned major surgery during the trial period up to month 18.
23. Has an active infection requiring systemic antiviral, antiparasitic, or antimicrobial therapy, and will not complete treatment before administration (day 1).
24. Has other medical conditions or comorbidities (e.g., malignancy, neuropsychiatric disorders, etc.) deemed by the administrator to potentially interfere with trial compliance or data interpretation.
25. History of multiple drug allergies, or a history of allergic reactions to any component or excipient of the investigational drug.
26. History of intolerance to subcutaneous (SC) injection.
27. Life expectancy < 2 years according to the administrator's clinical judgment. Contraception, Pregnancy, and Breastfeeding
28. Unwilling to adhere to contraceptive requirements during the trial.
29. Pregnant or breastfeeding female patients.
Use of Alcohol and Illegal Substances
30. Unwilling or unable to restrict alcohol consumption throughout the trial.
Exclude individuals with daily alcohol intake > 2 units during the trial (unit: 1 glass of wine [approx. 125 mL] = 1 serving of spirits [approx. 1 fluid ounce (29.574 mL)] = ½ pint of beer [approx. 284 mL]).
31. History of alcohol use disorder within the 12 months immediately preceding screening, as determined by the administrator.
32. Use of illegal substances within the past 5 years, which the administrator deems would interfere with adherence to trial procedures or follow-up visits.
The Estimated Number of Participants
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Taiwan
6 participants
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Global
125 participants
