TRITON-PN: A Study to Evaluate the Efficacy and Safety of Nucresiran in Patients With Hereditary Transthyretin Amyloidosis With Polyneuropathy

Purpose

The purpose of this study is to: - Determine the efficacy of nucresiran in patients with hATTR-PN by evaluating the effect on neurologic impairment, quality of life, nutritional status, disability, and gait speed - Demonstrate superiority of nucresiran compared to in-study vutrisiran with respect to serum transthyretin (TTR) levels

Conditions

  • Hereditary Transthyretin-Mediated Amyloidosis With Polyneuropathy
  • hATTR-PN

Eligibility

Eligible Ages
Between 18 Years and 85 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Nucresiran 300 mg 		Patients will be administered nucresiran 300 mg subcutaneously (SC) once every 6 months (q6M) during the Treatment Period and Treatment Extension Period
  • Drug: Nucresiran
    Nucresiran 300 mg administered SC q6M
    Other names:
    • ALN-TTRSC04
  • Drug: Vutrisiran
    Vutrisiran 25 mg administered SC q3M
    Other names:
    • AMVUTTRA
    • ALN-TTRSC02
Active Comparator
Vutrisiran 25 mg followed by Nucresiran 300 mg 		Patients will be administered vutrisiran 25 mg SC every 3 months (q3M) during the Treatment Period followed by nucresiran 300 mg SC q6M during the Treatment Extension Period
  • Drug: Nucresiran
    Nucresiran 300 mg administered SC q6M
    Other names:
    • ALN-TTRSC04
  • Drug: Vutrisiran
    Vutrisiran 25 mg administered SC q3M
    Other names:
    • AMVUTTRA
    • ALN-TTRSC02

Recruiting Locations

Clinical Trial Site
Boston, Massachusetts 02118

More Details

Status
Recruiting
Sponsor
Alnylam Pharmaceuticals

Study Contact

Clinical Trial Information Line
1-877-ALNYLAM
clinicaltrials@alnylam.com