Transthyretin Amyloidosis With Cardiomyopathy
Conditions
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
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
Interventions
DRUGNucresiran
Nucresiran 300 mg administered SC q6M
DRUGSterile Normal Saline (0.9% NaCl)
Sterile Normal Saline (0.9% NaCl) administered SC once q6M
Sponsors
Alnylam Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite outcome of all-cause mortality and recurrent cardiovascular [CV] events (CV hospitalizations and urgent heart failure [HF] visits) | Baseline to end of double-blind period (estimated 32 months, maximum 5 years) | All-cause mortality and recurrent CV events (CV hospitalizations and urgent HF visits) will be compared between treatment groups using an Andersen-Gill model. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to first CV event (CV hospitalizations and urgent HF visits) or all-cause mortality | Baseline to end of double-blind period (estimated 32 months, maximum 5 years) | — |
| All-cause mortality | Baseline to end of double-blind period (estimated 32 months, maximum 5 years) | — |
| Recurrent CV events (CV hospitalizations and urgent HF visits) | Baseline to end of double-blind period (estimated 32 months, maximum 5 years) | — |
| Change from baseline in Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) | Baseline to Month 30 | 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. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Czechia, Denmark, France, Germany, Greece, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Malaysia, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Romania, Slovakia, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTClinical Trial Information Line
STUDY_DIRECTORMedical Director
Alnylam Pharmaceuticals
Outcome results
None listed