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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

RecruitingPhase 3

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

Who can join

Ages 18 and older · All sexes

Full eligibility criteria
Inclusion Criteria:

1. Male or female.
2. Age 18 years or above at the time of signing the informed consent.
3. 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).
4. 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.
5. Completed more than 50 meters on the 6MWT at screening.

Exclusion Criteria:

1. Known or suspected hypersensitivity to study intervention(s) or related products.
2. Current or previous participation (dosing with active treatment) in a study for an investigational ATTR depleting drug or ATTR gene editing therapy.
3. Total bilirubin greater than 3 times the upper limit of normal (ULN) at screening.
4. Current diagnosis or history of amyloid light chain, other non-ATTR amyloidosis, known leptomeningeal amyloidosis, or multiple myeloma.
5. 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).
6. Currently hospitalised or hospitalised within 14 days prior to screening.
7. Currently treated with positive inotropic medication.
8. Uncorrected, severe, haemodynamically significant, left-sided heart valve disease.
9. 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.
10. Prior solid organ transplant or planned solid organ transplant during the study.
11. Left ventricular ejection fraction (LVEF) less than 30 percent as assessed by centralised review of echocardiography.
12. 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.
13. 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).

About the study

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.

What is being tested

Sponsor: Novo Nordisk A/S · Participants: 1,280 · Started: Oct 2, 2025

Contact the study team

Official record on ClinicalTrials.gov — NCT07207811

Locations in the U.S.

ArizonaMayo Clinic Hospital, Phoenix (Not yet recruiting)
CaliforniaUniversity of California San Diego (UCSD) - Sulpizio Cardiovascular Center (SCVC), La Jolla
Cedars-Sinai Medical Center - Samuel Oschin Comprehensive Cancer Institute, Los Angeles (Not yet recruiting)
Keck School of Medicine USC - Healthcare Consultation Center 2 (HCCII), Los Angeles (Not yet recruiting)
UCI Medical Center, Orange (Not yet recruiting)
Profound Research LLC at Southern California Heart Specialists, Pasadena
University of California, San Francisco Medical Center, San Francisco
NorthBay Clinical Research, Santa Rosa
Lucile Packard Children's Hospital, Stanford
ConnecticutYale University School of Medicine, New Haven
District of ColumbiaMedStar Heart & Vascular Institute (MHVI) - MedStar Washington Hospital Center, Washington D.C.
FloridaUF Health Heart and Vascular Hospital, Gainesville
GeorgiaNortheast Georgia Heart Center, Pc (Nghc), Gainesville
HawaiiThe Queen's Medical Center, Honolulu
IllinoisNorthwestern University Clinical and Translational Sciences Institute, Chicago
The University of Chicago Medicine, Chicago
Endeavor Health - Glenbrook Hospital, Glenview
IndianaIndiana University (IU) Health - Methodist Professional Center II, Indianapolis
LouisianaLCMC - LSU University Medical Center New Orleans LCMC Center, New Orleans
MarylandJohn Hopkins Medicine, Baltimore (Not yet recruiting)
University of Maryland Medical Center (UMMC) - Children's Hospital (UMCH), Baltimore
MassachusettsMassachusetts General Hospital, Boston
Tufts Medical Center, Boston
MichiganUniversity of Michigan Health System, Ann Arbor
Henry Ford Health, Detroit
Profound Research, Farmington Hills
MinnesotaMayo Clinic, Rochester
MissouriSaint Luke's Hospital of Kansas City, Kansas City
Saint Louis University, St Louis (Not yet recruiting)
Washington University School of Medicine, St Louis
NebraskaUniversity of Nebraska Medical Center, Omaha
New YorkNorth Shore University Hospital, Northwell Health, Manhasset
Columbia University Medical Center, New York
Mount Sinai Medical Center, New York
NYU Langone Health, New York
Weill Medical College Of Cornell University, New York
Laurelton Heart Specialist, PC, Rosedale
Yeshiva University - Albert Einstein College of Medicine - Montefiore Medical Center (MMC), The Bronx
North CarolinaDuke University Health System, Durham
OhioThe Carl and Edyth Lindner-Center for Research and Education at The Christ Hospital, Cincinnati
Cleveland Clinic - Taussig Cancer Institute, Cleveland
OhioHealth Riverside Methodist Hospital, Columbus
OregonOregon Health and Science University, Portland
PennsylvaniaJefferson Health, Abington
Lehigh Valley Hospital, Allentown
Penn State Milton S.Hershey Medical Center - Penn State Hershey Cancer Institute, Hershey (Not yet recruiting)
The Heart Group of Lancaster General Health, Lancaster (Not yet recruiting)
Penn Medicine: University of Pennsylvania Health System, Philadelphia
South CarolinaPrisma Health, Greenville
TennesseeSaint Thomas Health, Nashville
TexasAscension Texas Cardiovascular Research Institute, Austin
St. Davids Heart and Vascular, Austin
Baylor Scott & White Research Institute - Annette C. and Harold C. Simmons Transplant Institute, Dallas
University of Texas Southwestern Medical Center, Dallas
Baylor St. Luke Medical Center, Houston
Houston Methodist Hospital, Houston
Baylor Scott & White The Heart Hospital, Plano
UtahIntermountain Healthcare - Intermountain Medical Center - C. DuWayne Schmidt Chest Clinic, Murray
VirginiaInova Fairfax Hospital - Inova Heart and Vascular Institute, Falls Church
Sentara Cardiovascular Research Institute, Norfolk
Virginia Commonwealth University Medical Center, Richmond
WashingtonProvidence Sacred Heart Medical Center and Children's Hospital, Spokane

From ClinicalTrials.gov, data retrieved Oct 2, 2026. Each study sets its own eligibility; the study team decides who can join.