125 Participants Needed

Nucresiran for Transthyretin Amyloidosis Polyneuropathy

(TRITON-PN Trial)

CT
Overseen ByClinical Trial Information Line
Age: 18+
Sex: Any
Trial Phase: Phase 3
Sponsor: Alnylam Pharmaceuticals
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of nucresiran for individuals with hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN), a condition that affects nerves and can impact movement and quality of life. Researchers seek to determine if nucresiran improves symptoms such as nerve damage and walking speed and if it is more effective at lowering a specific protein in the blood compared to another treatment, vutrisiran. Participants will either receive nucresiran directly or start with vutrisiran before switching to nucresiran. Suitable candidates have a diagnosis of hATTR-PN and experience nerve-related issues from this condition. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Earlier studies found that patients using vutrisiran, a medicine for transthyretin amyloidosis, tolerated it well and found it safe even after nearly five years. Although direct safety data for nucresiran is not yet available, its similarity to existing treatments suggests it might also be well-tolerated. However, since nucresiran remains under testing and lacks approval from health authorities, researchers continue to closely study its safety. So far, similar treatments have not reported any serious safety issues.12345

Why do researchers think this study treatment might be promising for polyneuropathy?

Researchers are excited about nucresiran for treating transthyretin amyloidosis polyneuropathy because it offers a novel approach to managing this condition. Unlike most treatments that require frequent administration, nucresiran is administered just twice a year, which could significantly improve patient convenience and adherence. Additionally, nucresiran works by silencing the gene responsible for the abnormal protein production, potentially offering a more direct and effective method of addressing the disease's root cause compared to existing treatments. This innovative mechanism has the potential to halt or even reverse the progression of nerve damage associated with the condition.

What evidence suggests that this trial's treatments could be effective for transthyretin amyloidosis polyneuropathy?

Research shows that nucresiran, which participants in this trial may receive, can significantly lower the amount of transthyretin (TTR) in the blood. High TTR levels are linked to hereditary transthyretin amyloidosis polyneuropathy (hATTR-PN), a condition affecting the nerves. In earlier studies, patients experienced a 90.3% drop in TTR levels just 15 days after a single dose of nucresiran. By day 29, the reduction increased to 96.5%, suggesting that the treatment might help slow the disease. Nucresiran reduces TTR production, potentially lessening nerve damage caused by the condition. Early findings suggest that nucresiran could improve symptoms and enhance the quality of life for people with hATTR-PN.16789

Who Is on the Research Team?

MD

Medical Director

Principal Investigator

Alnylam Pharmaceuticals Inc

Are You a Good Fit for This Trial?

This trial is for patients with hereditary transthyretin amyloidosis who have polyneuropathy. They must have a specific TTR gene variant, a certain level of nerve impairment, and be able to perform daily activities at least 60% as well as a healthy person.

Inclusion Criteria

I have been diagnosed with hereditary ATTR amyloidosis with polyneuropathy.
Has a neuropathy impairment score (NIS) of 5 to 130 (inclusive)
I have hATTR amyloidosis with nerve damage due to a TTR gene variant.
See 1 more

Exclusion Criteria

My heart condition limits my physical activity significantly.
My kidney function is low, with an eGFR of 30 mL/min/1.73m^2 or less.
I have a condition causing nerve damage unrelated to my cancer.
See 4 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either nucresiran 300 mg SC every 6 months or vutrisiran 25 mg SC every 3 months

18 months
Visits every 3 to 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Extension

Participants may continue receiving nucresiran 300 mg SC every 6 months

Long-term

What Are the Treatments Tested in This Trial?

Interventions

  • Nucresiran

Trial Overview

The study tests Nucresiran's effectiveness on nerve damage, quality of life, nutrition, disability, and walking speed in hATTR-PN patients. It aims to show that Nucresiran is better than Vutrisiran at reducing serum TTR levels.

How Is the Trial Designed?

2

Treatment groups

Experimental Treatment

Active Control

Group I: Nucresiran 300 mgExperimental Treatment1 Intervention
Group II: Vutrisiran 25 mg followed by Nucresiran 300 mgActive Control2 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

Alnylam Pharmaceuticals

Lead Sponsor

Trials
81
Recruited
16,100+

Dr. Yvonne Greenstreet

Alnylam Pharmaceuticals

Chief Executive Officer since 2021

MD from the University of Leeds, MBA from INSEAD

Dr. Pushkal Garg

Alnylam Pharmaceuticals

Chief Medical Officer since 2016

MD from Columbia University

Citations

TRITON-PN: A Study to Evaluate the Efficacy and Safety of ...

The purpose of this study is to: Determine the efficacy of nucresiran in patients with hATTR-PN by evaluating the effect on neurologic impairment, ...

Alnylam Pharmaceuticals Press Release | May 12, 2025

The Company will present the latest data from its flagship transthyretin amyloidosis (TTR) franchise at the upcoming Heart Failure 2025 Congress.

Transthyretin Amyloid Cardiomyopathy: The Plot Thickens ...

The phase I trial of six participants supported the safety and plausibility of this therapy, demonstrating a mean 52% reduction in serum TTR ...

New study tests nucresiran's potential to slow nerve damage

By reducing TTR protein production, nucresiran is expected to slow disease progression in FAP and other forms of ATTR amyloidosis, hereditary or ...

Alnylam Announces Interim Phase 1 Data of Nucresiran (ALN ...

In subjects receiving a single 300 mg dose of nucresiran, mean serum TTR reduction of 90.3% was observed at Day 15, 96.5% at Day 29, and 92.6% ...

Nov 17, 2024 Press Release for Alnylam

The safety and efficacy of nucresiran have not been established or evaluated by the FDA, EMA or any other health authority. About ATTR.

Efficacy and safety of patisiran for ATTRv-PN: a systematic ...

Patisiran is a small interfering RNA (siRNA), offering potential as a genetic-level therapy for hereditary transthyretin amyloidosis with polyneuropathy (ATTRv ...

Realizing the therapeutic potential of rapid knockdown ...

Transthyretin amyloidosis (ATTR) is a progressive, debilitating, and fatal disease caused by ongoing accumulation of toxic transthyretin (TTR) ...

Long-Term Vutrisiran Appears Safe and Well-Tolerated in ...

Vutrisiran is well-tolerated and has an acceptable safety profile in patients with ATTR who are treated with it for up to 58 months.