variant or wild-type transthyretin (TTR) amyloidcardiomyopathy
Conditions
Interventions
Control group:Placebo
Experimental group:NNC6019-001
Sponsors
Peking Union Medical College Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Male or female. 2. At least 18 years old at the time of signing the informed consent. 3. Diagnosed with ATTR-CM (ATTRwt or ATTRv), with cardiac amyloid infiltration, increased left ventricular (LV) wall thickness, and HF. Note: The target recruitment for ATTRv is approximately 15% of the study population. (1) Cardiac amyloid infiltration is defined as: 1) Positive TTR amyloid cardiac biopsy, or 2) PYP/DPD/HMDP scintigraphy combined with single-photon emission computed tomography (SPECT/CT) showing grade 2 or 3 cardiac uptake, with positive TTR amyloid extracardiac biopsy, or 3) PYP/DPD/HMDP scintigraphy combined with SPECT/CT showing grade 2 or 3 cardiac uptake, with normal serum free light chain ratio and negative serum and urine protein electrophoresis immunofixation (SPIE and UPIE). Note: Non-invasive diagnostic pathway results will be centrally reviewed and confirmed by experts; Bone scintigraphy will use technetium-99m (99mTc)-labeled pyrophosphate (99m Tc-PYP)/99mTc-labeled 3,3-diphosphono-1,2-propane-dicarboxylic acid (99m Tc-DPD)/99mTc-labeled hydroxymethylene diphosphonate (99mTc-HMDP); (2) Increased LV wall thickness, with echocardiographic central assessment showing septal wall thickness >= 12 mm. (3) Chronic HF (New York Heart Association [NYHA] class I-IV), requiring ongoing loop diuretic therapy, including: 1) At least one documented HF hospitalization, or 2) History of HF, manifested as volume overload or elevated cardiac filling pressure (e.g., elevated jugular venous pressure, shortness of breath, X-ray or auscultatory signs of pulmonary congestion, or peripheral edema); 4. Receiving stable CV medication for at least 4 weeks prior to randomization visit (defined as dose adjustment not exceeding 50% and no change in drug class), except for diuretics. 5. NT-proBNP concentration >=1000 pg/mL at screening. Note: Subjects with NT-proBNP levels between 1000-2000 pg/mL may be enrolled until reaching 35% of the total study population. 6. Walking distance >50 meters in the 6MWT at screening.
Exclusion criteria
Exclusion criteria: 1. Known or suspected hypersensitivity to the study intervention or related products. 2. Currently or previously participated in a study involving ATTR-depletion drugs or ATTR gene editing therapy (receiving active treatment drugs). 3. Total bilirubin >3× the upper limit of normal (ULN) at screening. 4. Currently diagnosed with or previously had light-chain amyloidosis, other non-ATTR amyloidosis, or known leptomeningeal amyloidosis or multiple myeloma. 5. Heart failure (HF) that the investigator considers not primarily caused by ATTR-CM, such as HF due to hypertension, valvular heart disease, or ischemic heart disease. 6. Currently hospitalized or hospitalized within 14 days prior to screening. 7. Currently receiving positive inotropic therapy. 8. Uncorrected severe and clinically significant left-sided valvular heart disease. Note: Echocardiography results within the past 2 years can be used. 9. Acute coronary syndrome, unstable angina, stroke, transient ischemic attack (TIA), coronary revascularization, cardiac device implantation, heart valve repair, or major surgery within 60 days prior to screening. 10. Have received or plan to receive a solid organ transplant during the study period. 11. Echocardiography results assessed by the center show left ventricular ejection fraction (LVEF) < 30%. 12. Malignant tumor or a history of malignant tumors within 3 years prior to screening (excluding basal cell or squamous cell skin cancer, cervical carcinoma in situ, in situ carcinoma/high-grade prostatic intraepithelial neoplasia (PIN), low-risk prostate cancer, or prostate cancer under stable treatment). 13. End-stage renal disease at screening (estimated glomerular filtration rate (eGFR) <15 ml/min/1.73m^2, or on long-term/intermittent hemodialysis or peritoneal dialysis).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of occurrences of the composite endpoint consisting; | — |
Secondary
| Measure | Time frame |
|---|---|
| Change in eGFR;Change in KCCQ-CSS;Change in KCCQ-OSS;Change in 6MWD;Number of occurrences of CV events;Change in annual rate of change in eGFR (eGFR slope total/chronic) j;Time to occurrence of CV death;Time to occurrence of all-cause death;Time to first occurrence of composite CKD endpoint;Time to hospitalisation due to HF or urgent HF visit;Time to CV events (CV hospitalisation b, c and urgent HF visit b);Change in UPCR;Number of occurrences of the composite endpoint consisting;Participant achieving threshold for clinically meaningful within-patient change from the participant’s perspective in KCCQ-CSS;Change in annual rate of change in eGFR (eGFR slope total/chronic);Participant achieving threshold for clinically meaningful within-patient change from the participant’s perspective in KCCQ-OSS;Participant achieving threshold for clinically meaningful within-patient change from the participant’s perspective in 6MWT;Change in stroke volume (SV);Change in NT-proBNP;Change in ATTR-QoL-SSF domain scores;Change in UACR;Change in circulating misTTR;Change in hs troponin I;Change in troponin T;Assessed as the win ratio;Change in subscales of KCCQ (total symptom score, physical limitations score, social limitations score, and QoL); | — |
Countries
China
Contacts
Public ContactZhang Shuyang
Peking Union Medical College Hospital
Outcome results
None listed