NCT07207811招募中3 期
CLEOPATTRA: Effects of NNC6019-0001 Versus Placebo on Cardiovascular Outcomes in Participants With Transthyretin Amyloid Cardiomyopathy (ATTR-CM)
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,280
- 试验地点
- 531
- 主要终点
- Composite Outcome of cardiovascular (CV) deaths and recurrent CV events (CV hospitalisations and urgent heart failure [HF] visits)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Sponsor staff involved in the clinical trial is masked according to company standard procedures.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
- •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.
排除标准
- •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).
研究组 & 干预措施
Placebo
Placebo Comparator
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.
干预措施: Placebo (NNC6019-0001) (Drug)
NNC6019-0001
Experimental
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.
干预措施: NNC6019-0001 (Drug)
结局指标
主要结局
Composite Outcome of cardiovascular (CV) deaths and recurrent CV events (CV hospitalisations and urgent heart failure [HF] visits)
时间窗: From baseline (week 0) to end of study (EOS) (up to approximately 4 years)
Measured as count of events.
Number of occurrences of composite endpoint of cardiovascular (CV) deaths and recurrent CV events (CV hospitalisations and urgent heart failure [HF] visits)
时间窗: From baseline (week 0) to end of study (EOS) (up to approximately 4 years)
Measured as count of events.
次要结局
- Change in Kansas city cardiomyopathy questionnaire- clinical summary score (KCCQ-CSS)(From baseline (week 0) to approximately 2 years)
- Change in Kansas city cardiomyopathy questionnaire- overall summary score (KCCQ-OSS)(From baseline (week 0) to approximately 2 years)
- Change in 6-minute walk distance (6MWD)(From baseline (week 0) to approximately 2 years)
- Number of occurrences of CV events (CV hospitalisation and urgent HF visits)(From baseline (week 0) to EOS (up to approximately 4 years))
- Time to occurrence of CV death(From baseline (week 0) to EOS (up to approximately 4 years))
- Time to occurrence of all-cause death(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(From baseline (week 0) to EOS (up to approximately 4 years))
- Time to hospitalisation due to HF or urgent HF visit(From baseline (week 0) to EOS (up to approximately 4 years))
- Time to CV events (CV hospitalisation and urgent HF visit)(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)(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(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(From baseline (week 0) to approximately 2 years)
- Change in troponin T(From baseline (week 0) to week 52)
- Participant achieving threshold for clinically meaningful within-patient change from the participant's perspective in 6-minute walk test (6MWT)(From baseline (week 0) to approximately 2 years)
- Change in stroke volume (SV)(From baseline (week 0) to week 52)
- Change in N-terminal pro B-type natriuretic peptide (NT-proBNP)(From baseline (week 0) to week 52)
- Change in high-sensitivity (hs) troponin I(From baseline (week 0) to week 52)
- Hierarchical composite of time to all-cause death as assessed by the win ratio(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(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(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(From baseline (Week 0) to approximately 2 years)
研究者
研究点 (531)
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