Nucresiran versus vutrisiran for hereditary transthyretin polyneuropathy
TRITON-PN: A Phase 3, Global, Randomized, Open-Label Study to Evaluate the Efficacy and Safety of Nucresiran in Patients With Hereditary Transthyretin-Mediated Amyloidosis With Polyneuropathy (hATTR-PN)
This trial tests whether nucresiran helps people with hereditary transthyretin-mediated amyloidosis with polyneuropathy by improving nerve function, symptoms, and quality of life and whether it lowers blood TTR more than vutrisiran.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 125 (estimated) |
| Ages | 18 Years to 85 Years |
| Sex | All |
| Sponsor | Alnylam Pharmaceuticals Industry-sponsored |
| Locations | 4 sites (Boston, Massachusetts and 3 other locations) |
| Trial ID | NCT07223203 on ClinicalTrials.gov |
What this trial studies
This Phase 3, head-to-head interventional trial compares the RNAi therapeutic nucresiran to vutrisiran in adults with genetically confirmed hATTR-PN. Eligible participants have a documented TTR gene variant, a neuropathy impairment score (NIS) between 5 and 130, and a Karnofsky Performance Status of at least 60%. Participants receive assigned treatment and are followed for changes in neurologic impairment, quality of life, nutritional status, disability, and gait speed as well as serum transthyretin levels. The study excludes people with prior or planned liver transplant, non-hATTR forms of amyloidosis, significant heart failure, marked liver enzyme or bilirubin elevation, severe renal impairment, or other known causes of neuropathy.
Who should consider this trial
Good fit: Ideal candidates are adults with genetically confirmed hereditary transthyretin amyloidosis with polyneuropathy, NIS 5–130, KPS ≥60%, and acceptable liver, kidney, and cardiac status who can attend a study site.
Not a fit: Patients with non-hATTR amyloidosis, leptomeningeal involvement, NYHA class >2 heart failure, severe liver or renal dysfunction, prior or planned liver transplant, or other causes of neuropathy are unlikely to benefit from this trial.
Why it matters
Potential benefit: If successful, nucresiran could reduce TTR levels and slow or improve neuropathy symptoms and related disability for people with hATTR-PN.
How similar studies have performed: Other RNAi therapies for hATTR-PN such as patisiran and vutrisiran have shown clinical benefit, so the RNAi approach is established, but nucresiran's superiority is unproven.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Has documented diagnosis of hATTR-PN * Has a diagnosis of hATTR amyloidosis with polyneuropathy with a documented TTR gene variant * Has a neuropathy impairment score (NIS) of 5 to 130 (inclusive) * Has a Karnofsky Performance Status (KPS) of ≥60% Exclusion Criteria: * Has had a liver transplant or is likely, in the opinion of the Investigator, to undergo liver transplantation during the Treatment Period of the study * Has known other (non-hATTR) forms of amyloidosis or clinical evidence of leptomeningeal amyloidosis * Has a New York Heart Association (NYHA) heart failure classification \>2 * Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2.5 upper limit of normal (ULN) * Has total bilirubin \>1.5 ULN * Has estimated glomerular filtration rate (eGFR) ≤30 mL/min/1.73m\^2 * Has other known causes of sensorimotor or autonomic neuropathy
Where this trial is running
Boston, Massachusetts and 3 other locations
- Clinical Trial Site — Boston, Massachusetts, United States (Recruiting)
- Clinical Trial Site — Dallas, Texas, United States (Not_yet_recruiting)
- Clinical Trial Site — Seoul, South Korea (Not_yet_recruiting)
- Clinical Trial Site — Stockholm, Sweden (Not_yet_recruiting)
Study contacts
- Study coordinator: Clinical Trial Information Line
- Email: clinicaltrials@alnylam.com
- Phone: 1-877-ALNYLAM
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.