Nucresiran for Amyloidosis

Recruiting at 37 trial locations

Overseen By Clinical Trial Information Line

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alnylam Pharmaceuticals

Must not be taking: TTR-lowering therapy

Disqualifiers: NYHA Class IV, PND Score IIIa, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

1250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called nucresiran to determine its effectiveness for a specific heart condition linked to amyloidosis, a disorder where abnormal proteins accumulate in organs. The trial aims to assess whether nucresiran can reduce deaths and heart-related issues and evaluate its impact on overall health and quality of life compared to a placebo (an inactive treatment). Potential participants include those with amyloidosis affecting the heart who have experienced heart failure requiring hospitalization or special medication. Participants will receive either nucresiran or a placebo injection every six months. As a Phase 3 trial, this study represents the final step before FDA approval, allowing participants to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial allows participants to continue taking approved TTR stabilizers for ATTR amyloidosis and background therapy for heart failure, as decided by the study doctor.

Is there any evidence suggesting that nucresiran is likely to be safe for humans?

Research shows that nucresiran is being tested for safety and effectiveness in people with transthyretin amyloidosis, a serious heart condition. Previous studies have not confirmed its safety, as major health authorities like the FDA have not reviewed or approved it. Ongoing research indicates that the safety profile of nucresiran is still under evaluation. However, its presence in advanced study stages suggests that earlier results might have indicated some level of safety for humans. Prospective participants should consider this information and discuss it with their doctor. ^{1 2 3 4 5}

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

Nucresiran is unique because it targets amyloidosis by silencing genes involved in the production of amyloid proteins, which is different from traditional treatments that mainly focus on managing symptoms. Unlike current options that may require frequent dosing, nucresiran is administered just once every six months via a subcutaneous injection, making it more convenient for patients. Researchers are excited about its potential to not only slow disease progression but also improve quality of life with fewer side effects and less frequent administration.

What evidence suggests that nucresiran might be an effective treatment for amyloidosis?

Research shows that nucresiran is a promising treatment for amyloidosis, particularly for heart-related issues. Previous studies found that a single 300 mg dose significantly lowers levels of the protein TTR, which accumulates in amyloidosis. This effect lasts over six months and remains consistent among different patients. In this trial, participants will receive either nucresiran 300 mg or a placebo during the double-blind period. The treatment aims to reduce the risk of heart problems and improve overall health. These findings suggest that nucresiran could effectively manage and possibly improve outcomes for people with amyloidosis. ^{1 2 4 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Alnylam Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for patients with a heart condition called transthyretin amyloidosis with cardiomyopathy. They must have certain levels of NT-proBNP, a documented diagnosis of ATTR amyloidosis, and may be on approved TTR stabilizers or diuretics for heart failure. Excluded are those with severe kidney issues, advanced polyneuropathy disability, or the most severe class of heart failure.

Inclusion Criteria

Has screening N-terminal prohormone B-type natriuretic peptide (NT-proBNP) >300 ng/L and <8500 ng/L; In patients with permanent or persistent atrial fibrillation, screening NT-proBNP >600 ng/L and <8500 ng/L

I have been diagnosed with ATTR amyloidosis affecting my heart.

I am currently taking medication for ATTR amyloidosis and may be on heart failure treatment.

Exclusion Criteria

My kidney function is very low.

I have severe nerve damage affecting my daily activities.

I have severe heart failure or moderate heart failure with a specific type of amyloidosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-Blind Treatment

Participants receive either nucresiran or placebo administered subcutaneously every 6 months

32 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label Extension

Participants receive nucresiran 300 mg administered subcutaneously every 6 months

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Nucresiran

Trial Overview The study tests Nucresiran's effectiveness against a placebo in reducing deaths and cardiovascular events in patients. It also looks at how it affects patient-reported health status and quality of life related to their heart condition.

How Is the Trial Designed?

Group I: Nucresiran 300 mg Experimental Treatment 1 Intervention

Participants will receive nucresiran 300 mg administered SC Q6M during the DB period, followed by nucresiran 300 mg administered SC q6M during the OLE period.

Group II: Placebo Placebo Group 2 Interventions

Participants will receive placebo administered subcutaneously (SC) once every 6 months (q6M) during the double-blind (DB) period, followed by nucresiran 300 mg administered SC q6M during the open-label extension (OLE) period.

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

1. investors.alnylam.com investors.alnylam.com/press-release?id=28541

Alnylam Announces Interim Phase 1 Data of Nucresiran (ALN ... These new results demonstrated that a single dose of nucresiran at 300 mg or higher led to rapid knockdown of serum TTR with low inter-patient variability.

2. clinicaltrialsarena.com clinicaltrialsarena.com/news/alnylam-nucresiran-attr-amyloidosis/

Alnylam reveals trial outcomes of nucresiran for ATTR ... The study showed significant reductions in serum TTR levels in subjects after a single dose, with sustained effects over time.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07052903

TRITON-CM: A Study to Evaluate Nucresiran in Patients ... TRITON-CM: A Study to Evaluate Nucresiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy. ClinicalTrials.gov ID NCT07052903.

4. finance.yahoo.com finance.yahoo.com/news/alny-reports-sustained-6-month-142600613.html

ALNY Reports Sustained 6-Month Efficacy Data From ... Alnylam shares interim phase I amyloidosis study data on nucresiran, showing rapid TTR reduction sustained for six months after a single ...

5. hfsa.org hfsa.org/sites/default/files/2025-07/CARDIOHUB_AMYLOIDOSIS_KEYTAKEAWAYS_2025_V5.pdf

KEY TAKEAWAYS Nucresiran reaches 96% knockdown by Day 29 in Phase 1 data and maintains over 6 months with minimal intrasubject variability. Brought to you by. Support for ...

6. investors.alnylam.com investors.alnylam.com/press-release?id=28986

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.

7. sciencedirect.com sciencedirect.com/science/article/pii/S2162253125001441

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) amyloid deposits ...