Testing NNC6019-0001 against a placebo for transthyretin amyloid cardiomyopathy (ATTR CM)

Inclusion

• +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.
• +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).
• +Male or female.
• +Age 18 years or above at the time of signing the informed consentInformed consentThe process of being told what taking part involves, then choosing freely.Read more →.
• +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).
• +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.
• +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).
• +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 randomisationRandomisedWhich group you go into is decided by chance, not by you or your doctor.Read more → visit.
• +Completed more than 50 meters on the 6MWT at screeningScreeningThe checks done before joining, to see whether a study fits.Read more →.