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L'essai clinique NCT07207811 (CLEOPATTRA) pour Cardiomyopathie Amyloïde à Transthyrétine (ATTR CM) est en recrutement. Consultez la vue en carte du Radar des Essais Cliniques et les outils de découverte par IA pour tous les détails, ou posez vos questions ici. | ||
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
CLEOPATTRA: Effects of NNC6019-0001 Versus Placebo on Cardiovascular Outcomes in Participants With Transthyretin Amyloid Cardiomyopathy (ATTR-CM)
- CLEOPATTRA
- NN6019-4958
- U1111-1315-5366 (Autre Identifiant) (World Health Organization (WHO))
- 2024-518899-31 (Autre Identifiant) (European Medical Agency (EMA))
| Groupe de participants/Bras | Intervention/Traitement |
|---|---|
ExpérimentalNNC6019-0001 Participants will receive NNC6019-0001 intravenously (IV). Participants will also have the option to continue any Standard of care (SoC) treatments as recommended by their medical health professional. | NNC6019-0001 NNC6019-0001 will be administered IV. |
Comparateur placeboPlacebo Participants will receive placebo matched to NNC6019-0001 IV. Participants will also have the option to continue any SoC treatments as recommended by their medical health professional. | Placebo (NNC6019-0001) Placebo matched to NNC6019-0001 will be administered IV. |
| Critères d'évaluation | Description de critères | Période |
|---|---|---|
Number of occurrences of composite endpoint of cardiovascular (CV) deaths and recurrent CV events (CV hospitalisations and urgent heart failure [HF] visits) | Measured as count of events. | From baseline (week 0) to end of study (EOS) (up to approximately 4 years) |
| Critères d'évaluation | Description de critères | Période |
|---|---|---|
Change in Kansas city cardiomyopathy questionnaire- clinical summary score (KCCQ-CSS) | 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. | From baseline (week 0) to approximately 2 years |
Change in Kansas city cardiomyopathy questionnaire- overall summary score (KCCQ-OSS) | 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. | From baseline (week 0) to approximately 2 years |
Change in 6-minute walk distance (6MWD) | Measured in meters. | From baseline (week 0) to approximately 2 years |
Number of occurrences of CV events (CV hospitalisation and urgent HF visits) | Measured as count of events. | From baseline (week 0) to EOS (up to approximately 4 years) |
Time to occurrence of CV death | Measured in months. | From baseline (week 0) to EOS (up to approximately 4 years) |
Time to occurrence of all-cause death | Measured in months. | 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 | 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. | From baseline (week 0) to EOS (up to approximately 4 years) |
Time to hospitalisation due to HF or urgent HF visit | Measured in months. | From baseline (week 0) to EOS (up to approximately 4 years) |
Time to CV events (CV hospitalisation and urgent HF visit) | Measured in months. | 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) | Measured as count of events. | 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 | Measured as count of participants. | 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 | Measured as count of participants. | From baseline (week 0) to approximately 2 years |
Participant achieving threshold for clinically meaningful within-patient change from the participant's perspective in 6-minute walk test (6MWT) | Measured as count of participants. | From baseline (week 0) to approximately 2 years |
Change in stroke volume (SV) | Measured in milliliter (mL). | From baseline (week 0) to week 52 |
Change in N-terminal pro B-type natriuretic peptide (NT-proBNP) | Measured as ratio to baseline. | From baseline (week 0) to week 52 |
Change in high-sensitivity (hs) troponin I | Measured in nanograms per milliliter (ng/mL). | From baseline (week 0) to week 52 |
Change in troponin T | Measured in ng/mL. | From baseline (week 0) to week 52 |
Hierarchical composite of time to all-cause death as assessed by the win ratio | Measured as total wins for each treatment group. | From baseline (week 0) up to approximately 2 years |
Hierarchical composite of number of CV events (CV hospitalisations or urgent HF visits) as assessed by the win ratio | Measured as total wins for each treatment group. | From baseline (week 0) up to approximately 2 years |
Hierarchical composite of difference > 15, > 10 and > 5 points in KCCQ-OSS as assessed by the win ratio | Measured as total wins for each treatment group. | From baseline (Week 0) to approximately 2 years |
Hierarchical composite of difference > 70 and > 30 meters in 6-minute walk test (6MWT) as assessed by the win ratio | Measured as total wins for each treatment group. | From baseline (Week 0) to approximately 2 years |
- 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.
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) scintigraphy with single-photon emission computed tomography (SPECT/CT) combined with an extracardiac biopsy positive for TTR amyloid, OR
- Grade 2 or 3 cardiac uptake at PYP/DPD/HMDP scintigraphy with SPECT/CT combined with normal serum free light chain ratio, and negative serum and urine protein electrophoresis with immunofixation (SPIE & UPIE).
Notes:
- Non-invasive diagnostic pathway will be confirmed by a centralised expert review.
- Bone tracer scintigraphy 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).
Increased LV wall thickness, as assessed by centralised review of echocardiography, showing interventricular septal wall thickness greater than or equal to 12 millimeter (mm).
Chronic HF (New York Heart Association [NYHA] Class I-IV) requiring ongoing treatment with a loop diuretic with:
- 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).
- 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.
- 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.
Note: Pre-existing echocardiogram up to 2 years old may be used.
- 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).
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