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

Alnylam Pharmaceuticals

Status and phase: Enrolling; Phase 3

Conditions: Transthyretin Amyloidosis With Cardiomyopathy

Treatments: Drug: Sterile Normal Saline (0.9% NaCl); Drug: Nucresiran

Study type: Interventional

Funder types: Industry

Identifiers

NCT07052903

2024-519917-72-00 (EU Trial (CTIS) Number)

ALN-TTRSC04-003

Details and patient eligibility

About

The purpose of this study is to:

• Evaluate the efficacy of nucresiran compared to placebo on reducing all-cause mortality and cardiovascular (CV) events
• Evaluate the efficacy of nucresiran compared to placebo on additional assessments of CV events and/or death
• Evaluate the efficacy of nucresiran compared to placebo on patient-reported health status and health-related quality of life

Enrollment: 1,250 estimated patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• Has documented diagnosis of ATTR amyloidosis with cardiomyopathy including those with hereditary ATTR (hATTR) or wild-type ATTR (wATTR) amyloidosis.
• Has medical history of heart failure (HF) with at least 1 prior hospitalization for HF or signs and symptoms that require treatment with a diuretic.
• 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.
• Patients may be receiving approved TTR stabilizers for ATTR amyloidosis (eg, tafamidis, acoramidis) and may be receiving background therapy for HF at the discretion of the Investigator.

Exclusion Criteria

• Has New York Heart Association (NYHA) Class IV HF; or NYHA Class III heart failure AND ATTR Amyloidosis Disease Stage 3.
• Has a polyneuropathy disability (PND) Score IIIa, IIIb, or IV.
• Has an estimated glomerular filtration rate eGFR of <30 mL/min/1.73m^2 at screening.
• Has received prior or currently receiving TTR-lowering therapy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,250 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Sterile Normal Saline (0.9% NaCl)

Drug: Nucresiran

Nucresiran 300 mg

Experimental group

Description:

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.

Treatment:

Drug: Nucresiran