TRITON-CM: A Study to Evaluate Nucresiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Alnylam Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

29 Oct 2025 → ongoing

Decision date (initial)

2025-10-20

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Alnylam Pharmaceuticals, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacokinetic, Efficacy, Pharmacodynamic

Evaluate the efficacy of nucresiran compared to placebo on reducing all-cause mortality and CV events

Secondary objectives 1

1. To evaluate the efficacy of nucresiran compared to placebo on: • Additional assessments of CV events and/or death • Patient-reported health status and health related QoL

Conditions and MedDRA coding

Transthyretin Amyloidosis with Cardiomyopathy (ATTR Amyloidosis with Cardiomyopathy)

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

IPD plan description

Alnylam's policy restricts intended sharing of IPD to phase II to-IV clincial studies and after marketing authorization of the drug.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1. Age 18 (or age of legal consent per local regulations, whichever is older) to 85 years, inclusive.
2. 2. Documented diagnosis of ATTR amyloidosis with cardiomyopathy, classified as either hATTR amyloidosis with cardiomyopathy or wtATTR amyloidosis with cardiomyopathy:
3. 3. Medical history of HF with at least 1 prior hospitalization for HF OR clinical evidence of HF (with or without hospitalization)
4. 4. Patients may be receiving approved TTR stabilizers for ATTR amyloidosis and may be receiving background therapy for HF but must be stable for at least 30 days prior to screening
5. 5. Patient is clinically stable, with no CV-related hospitalizations within 6 weeks prior to randomization
6. 6. Screening 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
7. 7. Patient is able to understand and is willing and able to comply with the study requirements and to provide written informed consent

Exclusion criteria 11

1. 1. Has known primary amyloidosis (AL amyloidosis) or leptomeningeal amyloidosis
2. 2. NYHA Class IV HF; or NYHA Class III heart failure AND ATTR Amyloidosis Disease Stage 3 (defined as NT-proBNP >3000 ng/L and eGFR <45 mL/min)
3. 3. Has a polyneuropathy disability Score IIIa, IIIb, or IV at the Screening visit.
4. 4. Has any of the following lab parameter at screening: a. AST or ALT levels ˃2.0×ULN; b. Total bilirubin >2.0×ULN; c. INR >1.5 (unless patients were on anticoagulant therapy in which case excluded if INR ˃3.5).
5. 5. Has an eGFR of <30 mL/min/1.73m2 at screening (calculation will be based on the CKD-EPI equation)
6. 6. Has known HIV infection or evidence of current or chronic HCV or HBV infection.
7. 7. Patients with current, prior or planning to receive TTR-lowering therapy, anti-TTR antibody treatment, diflunisal, or participating in another investigational study (must meet washout periods of previous treatment to be included).
8. 8. Patients with the following medical conditions: • significant non-TTR cardiomyopathies, unstable CHF, recent acute coronary syndrome, ventricular arrhythmias, pacemaker-indicated nodal dysfunction, or uncontrolled high blood pressure are excluded from the study. • untreated hypo- or hyperthyroidism • active infections requiring systemic antiviral, antiparasitic, or antimicrobial therapy that will not be completed before dosing • Prior or anticipated ( 12 months after randomization) organ transplant or implantation of LVAD • multiple drug allergies or history of allergic reaction to any component of study drug • intolerance to SC injection • other medical conditions or comorbidities that could interfere with study compliance or data interpretation, or a life expectancy of <2 years due to any non-cardiovascular condition
9. 9. Unwilling to comply with the contraceptive requirements during the study;
10. 10. Female patient is pregnant, planning a pregnancy, or breastfeeding
11. 11. Unwilling or unable to limit alcohol consumption, with a history of alcohol use disorder within the last 12 months, or a history of illicit drug use within the past 5 years that could interfere with study compliance

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Composite outcome of all-cause mortality and recurrent CV events (CV hospitalizations and urgent HF visits)

Secondary endpoints 1

1. •Time to first CV event (CV hospitalizations and urgent HF visits) or all-cause mortality •All-cause mortality •Recurrent CV events •Change from baseline in KCCQ-OS

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Alnylam Pharmaceuticals Inc.

Sponsor organisation

Alnylam Pharmaceuticals Inc.

Address

300 3rd Street

City

Cambridge

Postcode

02142-1103

Country

United States

Scientific contact point

Organisation

Alnylam Pharmaceuticals Inc.

Contact name

Alnylam Clincial Trial Information Line

Public contact point

Organisation

Alnylam Pharmaceuticals Inc.

Contact name

Alnylam Clincial Trial Information Line

Third parties 15

Locations

18 EU/EEA countries · 124 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 198 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

25 submissions — initial application plus substantial / non-substantial modifications