Recruiting
Phase 3

Nucresiran

Sponsor:

Alnylam Pharmaceuticals

Code:

NCT07052903

Conditions

Transthyretin Amyloidosis With Cardiomyopathy

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Nucresiran

Sterile Normal Saline (0.9% NaCl)

Study Details

Brief summary:

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

Conditions

Transthyretin Amyloidosis With Cardiomyopathy

Study ID

NCT07052903

Start date

Jul 2, 2025

Status verified date

Aug, 2026

Completion date

Nov 30, 2032

Anticipated

Primary completion date

May 28, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

1750 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

placebo comparator: Placebo

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.

experimental: Nucresiran 300 mg

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.

Interventions

Nucresiran

Nucresiran 300 mg administered SC q6M

Sterile Normal Saline (0.9% NaCl)

Sterile Normal Saline (0.9% NaCl) administered SC once q6M

Primary outcome measure

  • Composite outcome of all-cause mortality and recurrent cardiovascular [CV] events (CV hospitalizations and urgent heart failure [HF] visits) [ Time Frame: Baseline to end of double-blind period (estimated 32 months, maximum 5 years) ]

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

La Jolla, California, United States, 92037

Clinical Trial Site

Recruiting

Laguna Hills, California, United States, 92653

Clinical Trial Site

Recruiting

Stanford, California, United States, 94305

Clinical Trial Site

Recruiting

Norwich, Connecticut, United States, 06360

Clinical Trial Site

Recruiting

Washington D.C., District of Columbia, United States, 20010

Clinical Trial Site

Recruiting

Brandon, Florida, United States, 33511

Clinical Trial Site

Recruiting

Miami, Florida, United States, 33125

Clinical Trial Site

Recruiting

Atlanta, Georgia, United States, 30309

Clinical Trial Site

Recruiting

Gainesville, Georgia, United States, 30501

Clinical Trial Site

Recruiting

Tucker, Georgia, United States, 30084

Clinical Trial Site

Recruiting

Chicago, Illinois, United States, 60612

Clinical Trial Site

Recruiting

Evanston, Illinois, United States, 60201

Clinical Trial Site

Recruiting

Indianapolis, Indiana, United States, 46202

Clinical Trial Site

Recruiting

Indianapolis, Indiana, United States, 46260

Clinical Trial Site

Recruiting

Kansas City, Kansas, United States, 66160

Clinical Trial Site

Recruiting

Baltimore, Maryland, United States, 21287

Clinical Trial Site

Recruiting

Boston, Massachusetts, United States, 02115

Clinical Trial Site

Recruiting

Boston, Massachusetts, United States, 02118

Clinical Trial Site

Recruiting

Detroit, Michigan, United States, 48202

Clinical Trial Site

Recruiting

Rochester, Minnesota, United States, 55905

Clinical Trial Site

Recruiting

St Louis, Missouri, United States, 63110

Clinical Trial Site

Recruiting

Manhasset, New York, United States, 11030

Clinical Trial Site

Recruiting

New York, New York, United States, 10029

Clinical Trial Site

Recruiting

New York, New York, United States, 10032

Clinical Trial Site

Recruiting

New York, New York, United States, 10065

Clinical Trial Site

Recruiting

The Bronx, New York, United States, 10467

Clinical Trial Site

Recruiting

Charlotte, North Carolina, United States, 28204

Clinical Trial Site

Recruiting

Cleveland, Ohio, United States, 44195

Clinical Trial Site

Recruiting

Columbus, Ohio, United States, 43210

Clinical Trial Site

Recruiting

Portland, Oregon, United States, 97239

Clinical Trial Site

Recruiting

Lancaster, Pennsylvania, United States, 17602

Clinical Trial Site

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Clinical Trial Site

Recruiting

Charleston, South Carolina, United States, 29425

Clinical Trial Site

Recruiting

Dallas, Texas, United States, 75246

Clinical Trial Site

Recruiting

Houston, Texas, United States, 77030

Clinical Trial Site

Recruiting

Plano, Texas, United States, 75024

Clinical Trial Site

Recruiting

Salt Lake City, Utah, United States, 84132

Clinical Trial Site

Recruiting

Charlottesville, Virginia, United States, 22903

Clinical Trial Site

Recruiting

Falls Church, Virginia, United States, 22042

Clinical Trial Site

Recruiting

Norfolk, Virginia, United States, 23507

Clinical Trial Site

Recruiting

Richmond, Virginia, United States, 23298

Clinical Trial Site

Recruiting

Spokane, Washington, United States, 99204

Clinical Trial Site

Recruiting

Calgary, Canada, T2N 4N1

Clinical Trial Site

Recruiting

London, Canada, N6A 5A5

Clinical Trial Site

Recruiting

Vancouver, Canada, V6Z 1Y6

More Information

Sponsor

Alnylam Pharmaceuticals

Last update posted

Aug 14, 2026

Last verified

Aug, 2026

Keywords

  • ATTR-CM
  • ATTR amyloidosis with cardiomyopathy
  • ATTR
  • Heriditary ATTR
  • hATTR
  • Wild-type ATTR
  • wATTR
  • Cardiomyopathy
  • Amyloidosis
  • TTR
  • Transthyretin
  • TTR-mediated amyloidosis
  • RNAi
  • RNAi therapeutic
  • TTR cardiomyopathy
  • V122i
  • TTR amyloidosis

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