Recruiting NCT07207811

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

Phase III Interventional Transthyretin Amyloid Cardiomyopathy (ATTR CM)

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: NNC6019-0001, Placebo (NNC6019-0001).
Who it may be relevant to: Registry conditions: Transthyretin Amyloid Cardiomyopathy (ATTR CM). Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Argentina, Australia, Belgium, Brazil +15
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

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Official title

CLEOPATTRA: Effects of NNC6019-0001 Versus Placebo on Cardiovascular Outcomes in Participants With Transthyretin Amyloid Cardiomyopathy (ATTR-CM)

Overview

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

Drug NNC6019-0001
NNC6019-0001 will be administered IV.
Drug Placebo (NNC6019-0001)
Placebo matched to NNC6019-0001 will be administered IV.

Primary outcome measures

Composite Outcome of cardiovascular (CV) deaths and recurrent CV events (CV hospitalisations and urgent heart failure [HF] visits) [Time frame: From baseline (week 0) to end of study (EOS) (up to approximately 4 years)]

Secondary outcome measures (12)

Change in Kansas city cardiomyopathy questionnaire- clinical summary score (KCCQ-CSS) [Time frame: From baseline (week 0) to approximately 2 years]
Change in Kansas city cardiomyopathy questionnaire- overall summary score (KCCQ-OSS) [Time frame: From baseline (week 0) to approximately 2 years]
Change in 6-minute walk distance (6MWD) [Time frame: From baseline (week 0) to approximately 2 years]
Number of occurrences of CV events (CV hospitalisation and urgent HF visits) [Time frame: From baseline (week 0) to EOS (up to approximately 4 years)]
Time to occurrence of CV death [Time frame: From baseline (week 0) to EOS (up to approximately 4 years)]
Time to occurrence of all-cause death [Time frame: From baseline (week 0) to EOS (up to approximately 4 years)]
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 [Time frame: From baseline (week 0) to EOS (up to approximately 4 years)]
Time to hospitalisation due to HF or urgent HF visit [Time frame: From baseline (week 0) to EOS (up to approximately 4 years)]
Time to CV events (CV hospitalisation and urgent HF visit) [Time frame: From baseline (week 0) to EOS (up to approximately 4 years)]
Number of occurrences of composite endpoint of CV deaths and recurrent CV events (CV hospitalisation, urgent HF visits, and outpatient HF visits) [Time frame: From baseline (week 0) to EOS (up to approximately 4 years)]
Participant achieving threshold for clinically meaningful within-patient change from the participant's perspective in KCCQ-CSS [Time frame: From baseline (week 0) to approximately 2 years]
Participant achieving threshold for clinically meaningful within-patient change from the participant's perspective in KCCQ-OSS [Time frame: From baseline (week 0) to approximately 2 years]

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.

a. Cardiac amyloid infiltration demonstrated by: i. Cardiac biopsy positive for TTR amyloid, OR ii. 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 iii. 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.

b. Increased LV wall thickness, as assessed by centralised review of echocardiography, showing interventricular septal wall thickness greater than or equal to 12 millimeter (mm).

c. Chronic HF (New York Heart Association \[NYHA\] Class I-IV): i. At least 1 documented hospitalisation for HF, OR ii. 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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Quadruple blind
Primary purpose: Treatment