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A study to evaluate the safety and effectiveness of nucresiran and vutrisiran in patients with hereditary transthyretin amyloidosis with polyneuropathy

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What is this study about?

This study focuses on a rare condition called Hereditary Transthyretin-Mediated Amyloidosis with Polyneuropathy. In this disease, an abnormal protein builds up in the body, which can cause damage to the nerves, leading to issues with movement and sensation. The purpose of the study is to evaluate the effectiveness and safety of a new medication called nucresiran.

Participants in the study will receive either nucresiran or vutrisiran, which is a currently used treatment for this condition. These medications are administered as a subcutaneous injection, meaning the medicine is injected into the fatty tissue just under the skin. During the study, the effects of these drugs on nerve function and the levels of a protein called transthyretin in the blood will be observed over time.

Who Can Join the Study?

  • You must be a man or a woman between the ages of 18 and 85 at the time you agree to join the study.
  • You must have been diagnosed with hereditary transthyretin-mediated amyloidosis with polyneuropathy, which is a rare disease caused by a specific change or mutation in the TTR gene (a piece of DNA that provides instructions for making a protein).
  • You must have a neuropathy impairment score (NIS) between 5 and 130. This score is a measurement used to check how much damage has occurred to your nerves (the body’s communication lines).
  • Your polyneuropathy disability (PND) score must be 3 or lower. This score measures how much the nerve damage affects your ability to perform daily activities.
  • You must have a Karnofsky Performance Status (KPS) score of 60% or higher. This is a scale used by doctors to measure your ability to carry out normal daily activities and your overall level of independence.
  • You must be able to understand the study requirements, be willing to follow them, and be able to provide written informed consent (a signed document stating you agree to participate).

Who Cannot Join the Study?

  • You have had a liver transplant (a surgery to replace a diseased liver with a healthy one) or the doctor believes you will need one during the study.
  • You have an uncontrolled cardiac arrhythmia (an irregular heartbeat) or unstable angina (chest pain that is unpredictable or worsening).
  • You have type 1 diabetes.
  • You have previously used or are currently using any TTR-lowering therapy (medicines designed to reduce a specific protein in the blood).
  • You have had type 2 diabetes mellitus for 5 years or longer.
  • You have hypothyroidism or hyperthyroidism (conditions where the thyroid gland is either underactive or overactive) that has not been treated.
  • You have had a major surgery in the last 3 months or have one planned during the first 18 months of the study.
  • You have an active infection that requires medicine like antivirals (for viruses), antiparasitics (for parasites), or antimicrobials (for bacteria) that will not be finished before the study starts.
  • You have other medical conditions that the doctor believes might make it difficult to follow the study rules or interfere with the results.
  • You have a history of multiple drug allergies or are allergic to any part of the study medicine.
  • You have a history of not being able to tolerate subcutaneous injections (shots given just under the skin).
  • Your estimated glomerular filtration rate (eGFR), which is a measure of how well your kidneys filter blood, is 30 mL/min/1.73m² or less.
  • You are currently taking tafamidis, acoramidis, doxycycline, or tauroursodeoxycholic acid, or you have taken them and have not waited at least 14 days since your last dose.
  • You are currently taking diflunisal, or you have taken it and have not waited at least 3 days since your last dose.
  • You have other forms of amyloidosis (a condition where abnormal proteins build up in organs) or evidence of it in the lining of the brain and spinal cord.
  • You have a heart failure classification higher than level 2, according to the New York Heart Association scale.
  • Your blood tests show ALT or AST (liver enzymes) that are more than 2.5 times the normal limit.
  • Your total bilirubin (a substance produced by the liver) is more than 1.5 times the normal limit, or more than 2 times the normal limit if you have Gilbert’s Syndrome (a common, harmless liver condition).
  • Your INR (a measure of how long it takes your blood to clot) is higher than 2.0.
  • Your platelet count (cells that help blood clot) is less than 50,000 per microliter.
  • Your absolute neutrophil count (a type of white blood cell that fights infection) is less than 1,500 cells per cubic millimeter.
  • The doctor believes your life expectancy is less than 2 years.
  • You are unwilling to follow the contraceptive (birth control) requirements during the study.
  • You are a female who is pregnant or breastfeeding.
  • Your vitamin B12 levels are lower than the normal range.
  • You are unwilling or unable to limit your alcohol consumption during the study.
  • You have a history of alcohol use disorder within the last 12 months.
  • You have used illicit substances (illegal drugs) in the last 5 years in a way that might interfere with the study.
  • You have an infection of the human immunodeficiency virus (HIV), hepatitis C, or hepatitis B.
  • You plan to start a TTR stabilizing therapy (medicine that helps stabilize a specific protein) within the first 18 months of joining the study.
  • You have previously received anti-TTR antibody treatment (medicines used to reduce specific proteins).
  • You have taken an investigational agent (a drug being tested in a study) within the last 30 days or are currently part of another study.
  • You have other causes of sensorimotor or autonomic neuropathy (nerve damage that affects movement, feeling, or automatic body functions) that your doctor believes is contributing to your condition.
  • You have had acute coronary syndrome (a sudden reduction in blood flow to the heart) within the past 3 months.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name City Country Status
Hospital Clinico San Carlos Madrid Spain
Universitaetsklinikum Heidelberg AöR Heidelberg Germany
Azienda Ospedaliero Universitaria Careggi Florence Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS Rome Italy
Bellvitge University Hospital L'hospitalet De Llobregat Spain
Unidade Local De Saúde De Santa Maria, E.P.E. Lisbon Portugal

Other Sites

Site Name City Country Status
Azienda Ospedaliera di Padova Padua Italy
Fondazione IRCCS Policlinico San Matteo Pavia Italy
Alexandra Hospital Athens Greece
Charite Universitaetsmedizin Berlin KöR Berlin Germany
Hospital Son Llatzer Palma Spain
A.O.U. Policlinico G. Martino Di Messina Messina Italy
Region Vaesterbotten Umea Sweden
The Cyprus Foundation For Muscular Dystrophy Research Agios Dometios Cyprus
University General Hospital Of Heraklion Heraklion Greece
Region Stockholm – SLSO Stockholm Sweden
Fondazione I.R.C.C.S. Istituto Neurologico Besta Milan Italy
Hopital Beaujon Clichy France
Bicetre Hospital Le Kremlin-Bicetre France
Aeufyhmeaa Phoedirp Hnardtwn Dp Mpztbgdpb Marseille France
Ciugoz Hhofazunnp Uyzhjeleqicel Dz Pyydn Emfifz Porto Portugal
Uvnxlnxemxzqeltanujdm Maocuwli Ayc Munster Germany
Hpsrfsce Vcii dzllgcua Barcelona Spain

Want to learn more about this study or check if you can participate? Contact us.

Trial status

Country Status Recruitment Start
Cyprus Cyprus
Recruiting
31.03.2026
France France
Recruiting
31.03.2026
Germany Germany
Not yet recruiting
31.03.2026
Greece Greece
Recruiting
31.03.2026
Ireland Ireland
Not yet recruiting
31.03.2026
Italy Italy
Recruiting
31.03.2026
Portugal Portugal
Recruiting
31.03.2026
Spain Spain
Recruiting
31.03.2026
Sweden Sweden
Recruiting
31.03.2026

Trial locations

Investigated drugs:

Nucresiran is an investigational medication being tested to see how well it works in reducing the symptoms of a condition called hereditary transthyretin-mediated amyloidosis with polyneuropathy. It is given as an injection under the skin.

Vutrisiran is a medication used as a comparison in this study to evaluate how effective the new treatment is. It is also administered as an injection under the skin.

Hereditary transthyretin-mediated amyloidosis with polyneuropathy – This is a rare genetic condition caused by mutations in the TTR gene. These mutations lead to the production of abnormal proteins that misfold and form deposits in various tissues throughout the body. In this specific form, these protein deposits primarily affect the nerves. As the disease progresses, the accumulation of these deposits causes damage to the peripheral nervous system. This damage typically leads to increasing impairment in nerve function and physical movement.

Trial ID:
2025-522544-40-00
Protocol code:
ALN-TTRSC04-004
Trial Phase:
Therapeutic confirmatory (Phase III)

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