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
* 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
Brief Title
TRITON-CM: A Study to Evaluate Nucresiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
1-877-ALNYLAM
Central Contact Email
clinicaltrials@alnylam.com
Central Contact Role
Contact
Central Contact Phone
1-877-256-9526
Central Contact Email
clinicaltrials@alnylam.com
Completion Date
Completion Date Type
Estimated
Conditions
Transthyretin Amyloidosis With Cardiomyopathy
Eligibility 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
* 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
Inclusion 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.
* 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.
Gender
All
Gender Based
false
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
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
85 Years
Minimum Age
18 Years
NCT Id
NCT07052903
Org Class
Industry
Org Full Name
Alnylam Pharmaceuticals
Org Study Id
ALN-TTRSC04-003
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
TRITON-CM: A Phase 3 Global, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Nucresiran in Patients With Transthyretin-Mediated Amyloidosis With Cardiomyopathy (ATTR Amyloidosis With Cardiomyopathy)
Primary Outcomes
Outcome Description
All-cause mortality and recurrent CV events (CV hospitalizations and urgent HF visits) will be compared between treatment groups using an Andersen-Gill model.
Outcome Measure
Composite outcome of all-cause mortality and recurrent cardiovascular [CV] events (CV hospitalizations and urgent heart failure [HF] visits)
Outcome Time Frame
Baseline to end of double-blind period (estimated 32 months, maximum 5 years)
Secondary Ids
Secondary Id
2024-519917-72-00
Secondary Outcomes
Outcome Time Frame
Baseline to end of double-blind period (estimated 32 months, maximum 5 years)
Outcome Measure
Time to first CV event (CV hospitalizations and urgent HF visits) or all-cause mortality
Outcome Time Frame
Baseline to end of double-blind period (estimated 32 months, maximum 5 years)
Outcome Measure
All-cause mortality
Outcome Time Frame
Baseline to end of double-blind period (estimated 32 months, maximum 5 years)
Outcome Measure
Recurrent CV events (CV hospitalizations and urgent HF visits)
Outcome Description
The KCCQ is a 23-item self-administered questionnaire quantifying 6 domains (symptoms, physical function, quality of life, social limitation, self-efficacy, and symptom stability) and 2 summary scores (clinical and overall summary \[OS\]). Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
Outcome Time Frame
Baseline to Month 30
Outcome Measure
Change from baseline in Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
85
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
James Tauras
Investigator Email
jtauras@montefiore.org
Investigator Department
Medicine
Investigator Division
Cardiology
Investigator Sponsor Organization
External
Study Department
Medicine
Study Division
Cardiology
Categories Mesh Debug
Brain, Spinal Cord & Nervous System --- HEART DISEASES
Heart/Cardiovascular --- HEART DISEASES
Blood Disorders --- CARDIOVASCULAR DISEASES
Blood & Bone Marrow Cancers --- CARDIOVASCULAR DISEASES
Heart/Cardiovascular --- CARDIOVASCULAR DISEASES
Diabetes --- METABOLIC DISEASES
Diabetes & Endocrine System --- METABOLIC DISEASES
MeSH Terms
CARDIOMYOPATHIES
AMYLOIDOSIS
HEART DISEASES
CARDIOVASCULAR DISEASES
PROTEOSTASIS DEFICIENCIES
METABOLIC DISEASES
NUTRITIONAL AND METABOLIC DISEASES