Recruiting
Phase 3

Nucresiran vs. Vutrisiran

Sponsor:

Alnylam Pharmaceuticals

Code:

NCT07223203

Conditions

Hereditary Transthyretin-Mediated Amyloidosis With Polyneuropathy

hATTR-PN

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Nucresiran

Vutrisiran

Study Details

Brief summary:

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

Study ID

NCT07223203

Start date

Dec 12, 2025

Status verified date

Aug, 2026

Completion date

Jun 12, 2031

Anticipated

Primary completion date

Dec 27, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

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

Enrollment

125 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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

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

Interventions

Nucresiran

Nucresiran 300 mg administered SC q6M

Vutrisiran

Vutrisiran 25 mg administered SC q3M

Primary outcome measure

  • Change from Baseline in the Modified Neuropathy Impairment Score +7 (mNIS+7) Compared to the External Placebo Group from the APOLLO Study (NCT01960348) at Month 9 [ Time Frame: Baseline and Month 9 ]

Central Contacts and Locations

Central contacts

Clinical Trial Information Line

1-877-ALNYLAMclinicaltrials@alnylam.com

Clinical Trial Information Line

1-877-256-9526clinicaltrials@alnylam.com

Locations

Clinical Trial Site

Recruiting

Aurora, Colorado, United States, 80045

Clinical Trial Site

Recruiting

Chicago, Illinois, United States, 60611

Clinical Trial Site

Recruiting

Baltimore, Maryland, United States, 21287

Clinical Trial Site

Recruiting

Boston, Massachusetts, United States, 02118

Clinical Trial Site

Recruiting

Rochester, Minnesota, United States, 55905

Clinical Trial Site

Recruiting

New York, New York, United States, 10032

Clinical Trial Site

Recruiting

Chapel Hill, North Carolina, United States, 27514

Clinical Trial Site

Recruiting

Dallas, Texas, United States, 75246

Clinical Trial Site

Recruiting

Houston, Texas, United States, 77030

Clinical Trial Site

Recruiting

Vancouver, Canada, V5Z 1M9

More Information

Sponsor

Alnylam Pharmaceuticals

Last update posted

Aug 14, 2026

Last verified

Aug, 2026

Keywords

  • Polyneuropathy
  • Amyloidosis
  • Transthyretin
  • TTR
  • RNAi therapeutic

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Alnylam Pharmaceuticals on 2026-08-14.