CLEOPATTRA: A Research Study to Look at the Effects of Treatment With a Medicine Called Coramitug (NNC6019-0001) in People With Heart Failure Due to Transthyretin Amyloid (ATTR) Amyloidosis

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.
Brief Title
CLEOPATTRA: A Research Study to Look at the Effects of Treatment With a Medicine Called Coramitug (NNC6019-0001) in People With Heart Failure Due to Transthyretin Amyloid (ATTR) Amyloidosis
Central Contacts
Central Contact Role
Contact
Central Contact Phone
(+1) 866-867-7178
Central Contact Email
clinicaltrials@novonordisk.com
Completion Date
Completion Date Type
Estimated
Conditions
Transthyretin Amyloid Cardiomyopathy (ATTR CM)
Eligibility Criteria
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) nuclear medicine imaging with single-photon emission computed tomography (SPECT) or SPECT/CT (preferably) combined with an extracardiac biopsy positive for TTR amyloid, OR
* Grade 2 or 3 cardiac uptake at PYP/DPD/HMDP nuclear medicine imaging with SPECT or SPECT/CT (preferably) combined with normal serum free light chain ratio, and negative serum and urine protein electrophoresis with immunofixation (SPIE \& UPIE)/or mass spectrometry based methods including mass fixation).

Notes:
* Non-invasive diagnostic pathway will be confirmed by a centralised expert review.
* Bone tracer nuclear medicine imaging with SPECT or SPECT/CT (preferably) 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).
* The eGFR adjusted acceptable serum free light chain ratio.
* Patients with Grade 2 or 3 cardiac uptake at PYP/DPD/HDMP nuclear imaging with SPECT or SPECT/CT (preferably) and evidence of monoclonal gammopathy of undetermined significance (MGUS; based on serum and urine protein electrophoresis and serum free light chains) will require endomyocardial biopsy with typing using mass spectrometry or immunohistochemistry to confirm presence of TTR protein in tissue.
* Timing of serum free light chain ratio, SPIE, UPIE and mass spectrometry-based methods including mass fixation should be within 12 months of SPECT or SPECT/CT nuclear imaging.
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):

* 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 that required or requires ongoing treatment with a diuretic).
* 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.
* 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).
Inclusion Criteria
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) nuclear medicine imaging with single-photon emission computed tomography (SPECT) or SPECT/CT (preferably) combined with an extracardiac biopsy positive for TTR amyloid, OR
* Grade 2 or 3 cardiac uptake at PYP/DPD/HMDP nuclear medicine imaging with SPECT or SPECT/CT (preferably) combined with normal serum free light chain ratio, and negative serum and urine protein electrophoresis with immunofixation (SPIE \& UPIE)/or mass spectrometry based methods including mass fixation).

Notes:
* Non-invasive diagnostic pathway will be confirmed by a centralised expert review.
* Bone tracer nuclear medicine imaging with SPECT or SPECT/CT (preferably) 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).
* The eGFR adjusted acceptable serum free light chain ratio.
* Patients with Grade 2 or 3 cardiac uptake at PYP/DPD/HDMP nuclear imaging with SPECT or SPECT/CT (preferably) and evidence of monoclonal gammopathy of undetermined significance (MGUS; based on serum and urine protein electrophoresis and serum free light chains) will require endomyocardial biopsy with typing using mass spectrometry or immunohistochemistry to confirm presence of TTR protein in tissue.
* Timing of serum free light chain ratio, SPIE, UPIE and mass spectrometry-based methods including mass fixation should be within 12 months of SPECT or SPECT/CT nuclear imaging.
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):

* 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 that required or requires ongoing treatment with a diuretic).
* 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.

Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT07207811
Org Class
Industry
Org Full Name
Novo Nordisk A/S
Org Study Id
NN6019-4958
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
CLEOPATTRA: Effects of NNC6019-0001 Versus Placebo on Cardiovascular Outcomes in Participants With Transthyretin Amyloid Cardiomyopathy (ATTR-CM)
Primary Outcomes
Outcome Description
Measured as count of events.
Outcome Measure
Composite Outcome of cardiovascular (CV) deaths and recurrent CV events (CV hospitalisations and urgent heart failure [HF] visits)
Outcome Time Frame
From baseline (week 0) to end of study (EOS) (up to approximately 4 years)
Secondary Ids
Secondary Id
U1111-1315-5366
Secondary Id
2024-518899-31
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
From baseline (week 0) to approximately 2 years
Outcome Measure
Change in Kansas city cardiomyopathy questionnaire- clinical summary score (KCCQ-CSS)
Outcome Description
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.
Outcome Time Frame
From baseline (week 0) to approximately 2 years
Outcome Measure
Change in Kansas city cardiomyopathy questionnaire- overall summary score (KCCQ-OSS)
Outcome Description
Measured in meters.
Outcome Time Frame
From baseline (week 0) to approximately 2 years
Outcome Measure
Change in 6-minute walk distance (6MWD)
Outcome Description
Measured as count of events.
Outcome Time Frame
From baseline (week 0) to EOS (up to approximately 4 years)
Outcome Measure
Number of occurrences of CV events (CV hospitalisation and urgent HF visits)
Outcome Description
Measured in months.
Outcome Time Frame
From baseline (week 0) to EOS (up to approximately 4 years)
Outcome Measure
Time to occurrence of CV death
Outcome Description
Measured in months.
Outcome Time Frame
From baseline (week 0) to EOS (up to approximately 4 years)
Outcome Measure
Time to occurrence of all-cause death
Outcome Description
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.
Outcome Time Frame
From baseline (week 0) to EOS (up to approximately 4 years)
Outcome Measure
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
Outcome Description
Measured in months.
Outcome Time Frame
From baseline (week 0) to EOS (up to approximately 4 years)
Outcome Measure
Time to hospitalisation due to HF or urgent HF visit
Outcome Description
Measured in months.
Outcome Time Frame
From baseline (week 0) to EOS (up to approximately 4 years)
Outcome Measure
Time to CV events (CV hospitalisation and urgent HF visit)
Outcome Description
Measured as count of events.
Outcome Time Frame
From baseline (week 0) to EOS (up to approximately 4 years)
Outcome Measure
Number of occurrences of composite endpoint of CV deaths and recurrent CV events (CV hospitalisation, urgent HF visits, and outpatient HF visits)
Outcome Description
Measured as count of participants.
Outcome Time Frame
From baseline (week 0) to approximately 2 years
Outcome Measure
Participant achieving threshold for clinically meaningful within-patient change from the participant's perspective in KCCQ-CSS
Outcome Description
Measured as count of participants.
Outcome Time Frame
From baseline (week 0) to approximately 2 years
Outcome Measure
Participant achieving threshold for clinically meaningful within-patient change from the participant's perspective in KCCQ-OSS
Outcome Description
Measured as count of participants.
Outcome Time Frame
From baseline (week 0) to approximately 2 years
Outcome Measure
Participant achieving threshold for clinically meaningful within-patient change from the participant's perspective in 6-minute walk test (6MWT)
Outcome Description
Measured in milliliter (mL).
Outcome Time Frame
From baseline (week 0) to week 52
Outcome Measure
Change in stroke volume (SV)
Outcome Description
Measured as ratio to baseline.
Outcome Time Frame
From baseline (week 0) to week 52
Outcome Measure
Change in N-terminal pro B-type natriuretic peptide (NT-proBNP)
Outcome Description
Measured in nanograms per milliliter (ng/mL).
Outcome Time Frame
From baseline (week 0) to week 52
Outcome Measure
Change in high-sensitivity (hs) troponin I
Outcome Description
Measured in ng/mL.
Outcome Time Frame
From baseline (week 0) to week 52
Outcome Measure
Change in troponin T
Outcome Description
Measured as total wins for each treatment group.
Outcome Time Frame
From baseline (week 0) up to approximately 2 years
Outcome Measure
Hierarchical composite of time to all-cause death as assessed by the win ratio
Outcome Description
Measured as total wins for each treatment group.
Outcome Time Frame
From baseline (week 0) up to approximately 2 years
Outcome Measure
Hierarchical composite of number of CV events (CV hospitalisations or urgent HF visits) as assessed by the win ratio
Outcome Description
Measured as total wins for each treatment group.
Outcome Time Frame
From baseline (Week 0) to approximately 2 years
Outcome Measure
Hierarchical composite of difference > 15, > 10 and > 5 points in KCCQ-OSS as assessed by the win ratio
Outcome Description
Measured as total wins for each treatment group.
Outcome Time Frame
From baseline (Week 0) to approximately 2 years
Outcome Measure
Hierarchical composite of difference > 70 and > 30 meters in 6-minute walk test (6MWT) as assessed by the win ratio
Start Date
Start Date Type
Actual
Status Verified Date
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Yogita Rochlani
Investigator Email
yrochlani@montefiore.org
Investigator Department
Medicine
Investigator Division
Cardiology
Investigator Sponsor Organization
External
Study Department
Medicine
Study Division
Cardiology