Transthyretin Amyloid Cardiomyopathy (ATTR CM)
Conditions
Brief summary
This study will find out if a new medicine called NNC6019-0001 can help reduce the risk of heart-related death and illness in participants with a condition called transthyretin amyloid cardiomyopathy (ATTR-CM), which affects the heart. Participants will either receive NNC6019-0001 or a placebo (a treatment with no active medicine), and which one they get is decided by chance. Everyone in the study will continue receiving their usual heart treatments as recommended by their doctor.
Interventions
DRUGNNC6019-0001
NNC6019-0001 will be administered IV.
Placebo matched to NNC6019-0001 will be administered IV.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Sponsor staff involved in the clinical trial is masked according to company standard procedures.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female. * Age 18 years or above at the time of signing the informed consent. * Have an established diagnosis of ATTR-CM (wild-type ATTR \[ATTRwt\] or variant ATTR \[ATTRv\]), with cardiac amyloid infiltration, increased left ventricular (LV) wall thickness, and HF. Note: Target ATTRv recruitment is approximately 15 percent of the study population. 1. Cardiac amyloid infiltration demonstrated by: * Cardiac biopsy positive for TTR amyloid, OR * Grade 2 or 3 cardiac uptake at pyrophosphate (PYP)/diphosphono-1,2-propanodicarboxylic acid (DPD)/ hydroxymethylene diphosphonate (HMDP) scintigraphy with single-photon emission computed tomography (SPECT/CT) combined with an extracardiac biopsy positive for TTR amyloid, OR * Grade 2 or 3 cardiac uptake at PYP/DPD/HMDP scintigraphy with SPECT/CT combined with normal serum free light chain ratio, and negative serum and urine protein electrophoresis with immunofixation (SPIE \& UPIE). Notes: * Non-invasive diagnostic pathway will be confirmed by a centralised expert review. * Bone tracer scintigraphy will be conducted using 99m-technetium (Tc)-labelled pyrophosphate (99mTc-PYP), 99mTc-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD), or 99mTc-labeled hydroxymethylene diphosphonate (99mTc-HMDP). 2. Increased LV wall thickness, as assessed by centralised review of echocardiography, showing interventricular septal wall thickness greater than or equal to 12 millimeter (mm). 3. Chronic HF (New York Heart Association \[NYHA\] Class I-IV) requiring ongoing treatment with a loop diuretic with: * At least 1 documented hospitalisation for HF, OR * History of HF manifested by signs or symptoms of volume overload or elevated intracardiac pressures (e.g., elevated jugular venous pressure, shortness of breath, signs of pulmonary congestion on x-ray or auscultation, or peripheral oedema). * Expected to be on stable cardiovascular medical therapy (defined as no greater than 50 percent dose adjustment and no categorical changes of medications), with the exception of diuretics, 4 weeks prior to the randomisation visit. * Completed more than 50 meters on the 6MWT at screening.
Exclusion criteria
* Known or suspected hypersensitivity to study intervention(s) or related products. * Current or previous participation (dosing with active treatment) in a study for an investigational ATTR depleting drug or ATTR gene editing therapy. * Total bilirubin greater than 3 times the upper limit of normal (ULN) at screening. * Current diagnosis or history of amyloid light chain, other non-ATTR amyloidosis, known leptomeningeal amyloidosis, or multiple myeloma. * HF not primarily caused by ATTR-CM (e.g., due to hypertension, valvular heart disease, or ischemic heart disease in the opinion of the investigator). * Currently hospitalised or hospitalised within 14 days prior to screening. * Currently treated with positive inotropic medication. * Uncorrected, severe, haemodynamically significant, left-sided heart valve disease. Note: Pre-existing echocardiogram up to 2 years old may be used. * Acute coronary syndrome, unstable angina, stroke, transient ischemic attack, coronary revascularisation, cardiac device implantation, cardiac valve repair, or major surgery within 60 days of screening. * Prior solid organ transplant or planned solid organ transplant during the study. * Left ventricular ejection fraction (LVEF) less than 30 percent as assessed by centralised review of echocardiography. * Presence or history of malignant neoplasm (other than basal or squamous cell skin cancer, in situ carcinomas of the cervix, carcinoma in situ/high-grade prostatic intraepithelial neoplasia \[PIN\], low-risk prostate cancer, or on stable therapy for prostate cancer) within 3 years before screening. * End-stage renal disease (estimated glomerular filtration rate \[eGFR\] less than 15 mL/min/1.73 m\^2 at screening, or chronic/intermittent haemodialysis or peritoneal dialysis).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of occurrences of composite endpoint of cardiovascular (CV) deaths and recurrent CV events (CV hospitalisations and urgent heart failure [HF] visits) | From baseline (week 0) to end of study (EOS) (up to approximately 4 years) | Measured as count of events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of occurrences of CV events (CV hospitalisation and urgent HF visits) | From baseline (week 0) to EOS (up to approximately 4 years) | Measured as count of events. |
| Time to occurrence of CV death | From baseline (week 0) to EOS (up to approximately 4 years) | Measured in months. |
| Change in Kansas city cardiomyopathy questionnaire- clinical summary score (KCCQ-CSS) | From baseline (week 0) to approximately 2 years | Measured as score on a scale. KCCQ-CSS is a score derived from a 23-item patient-reported outcome (PRO) measure assessing health status in individuals with HF. The score ranges from 0 to 100, with higher scores indicating better health status. |
| Change in Kansas city cardiomyopathy questionnaire- overall summary score (KCCQ-OSS) | From baseline (week 0) to approximately 2 years | Measured as score on a scale. KCCQ-OSS is a score derived from a 23-item PRO measure assessing health status in individuals with HF. The score ranges from 0 to 100, with higher scores indicating better health status. |
| Change in 6-minute walk distance (6MWD) | From baseline (week 0) to approximately 2 years | Measured in meters. |
| Time to first occurrence of composite CKD endpoint: CV death, onset of a persistent decline in eGFR of ≥30% from baseline, onset of a persistent eGFR <15 mL/min/1.73 m^2, or initiation of chronic KRT, including dialysis or kidney transplantation | From baseline (week 0) to EOS (up to approximately 4 years) | Measured in months. Composite chronic kidney disease (CKD) endpoint comprised of (1) CV death, (2) onset of a persistent decline in estimated glomerular filtration rate (eGFR) of greater than or equal to 30 percent (%) from baseline, (3) onset of a persistent eGFR less than or equal to 15 milliliters per minute per 1.73 square meters (mL/min/1.73 m\^2), or (4) initiation of chronic kidney replacement therapy (KRT), including dialysis or kidney transplantation. |
| Time to hospitalisation due to HF or urgent HF visit | From baseline (week 0) to EOS (up to approximately 4 years) | Measured in months. |
| Time to CV events (CV hospitalisation and urgent HF visit) | From baseline (week 0) to EOS (up to approximately 4 years) | Measured in months. |
| Number of occurrences of composite endpoint of CV deaths and recurrent CV events (CV hospitalisation, urgent HF visits, and outpatient HF visits) | From baseline (week 0) to EOS (up to approximately 4 years) | Measured as count of events. |
| Participant achieving threshold for clinically meaningful within-patient change from the participant's perspective in KCCQ-CSS | From baseline (week 0) to approximately 2 years | Measured as count of participants. |
| Participant achieving threshold for clinically meaningful within-patient change from the participant's perspective in KCCQ-OSS | From baseline (week 0) to approximately 2 years | Measured as count of participants. |
| Participant achieving threshold for clinically meaningful within-patient change from the participant's perspective in 6-minute walk test (6MWT) | From baseline (week 0) to approximately 2 years | Measured as count of participants. |
| Change in stroke volume (SV) | From baseline (week 0) to week 52 | Measured in milliliter (mL). |
| Change in N-terminal pro B-type natriuretic peptide (NT-proBNP) | From baseline (week 0) to week 52 | Measured as ratio to baseline. |
| Change in high-sensitivity (hs) troponin I | From baseline (week 0) to week 52 | Measured in nanograms per milliliter (ng/mL). |
| Change in troponin T | From baseline (week 0) to week 52 | Measured in ng/mL. |
| Hierarchical composite of time to all-cause death as assessed by the win ratio | From baseline (week 0) up to approximately 2 years | Measured as total wins for each treatment group. |
| Hierarchical composite of number of CV events (CV hospitalisations or urgent HF visits) as assessed by the win ratio | From baseline (week 0) up to approximately 2 years | Measured as total wins for each treatment group. |
| Hierarchical composite of difference > 15, > 10 and > 5 points in KCCQ-OSS as assessed by the win ratio | From baseline (Week 0) to approximately 2 years | Measured as total wins for each treatment group. |
| Time to occurrence of all-cause death | From baseline (week 0) to EOS (up to approximately 4 years) | Measured in months. |
| Hierarchical composite of difference > 70 and > 30 meters in 6-minute walk test (6MWT) as assessed by the win ratio | From baseline (Week 0) to approximately 2 years | Measured as total wins for each treatment group. |
Countries
Argentina, Australia, Belgium, Brazil, Canada, China, Czechia, Denmark, France, Germany, Ireland, Italy, Japan, Netherlands, Poland, South Korea, Spain, Sweden, United Kingdom, United States
Contacts
CONTACTNovo Nordisk
STUDY_DIRECTORClinical Transparency (dept. 2834)
Novo Nordisk A/S
Outcome results
None listed