Efficacy and Safety of NNC6019-0001 at Two Dose Levels in Participants With Transthyretin Amyloid Cardiomyopathy (ATTR CM)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 105
- 试验地点
- 71
- 主要终点
- Change in N-terminal-pro brain natriuretic peptide (NT-proBNP)
研究概览
简要总结
This study is testing a potential new medicine, NNC6019-0001, for people who have a heart disease due to TTR amyloidosis.The study will look at if this medicine can reduce the symptoms of a heart disease due to TTR amyloidosis, such as heart failure. Participants will either get NNC6019-0001 (apotential new medicine) or placebo (a medicine which has no effect on the body). Which treatment participants get is decided by chance. The chance of getting NNC6019-0001 is two times higher than getting placebo. NNC6019-0001 is not yet approved in any country or region in the world. It is a new medicine that doctors cannot prescribe yet. Participants will get an infusion of the study medicine 13 times, once every 4 weeks. The study will last for about 64 weeks after the first dose of medicine. Participants cannot participate in this study if they have a heart disease other than a heart disease due to TTR amyloidosis.
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)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female.
- •Age greater than or equal to (>=) 18 to less than (<) 85 years at the time of signing informed consent.
- •Have an established diagnosis of Transthyretin amyloid cardiomyopathy (ATTR CM) with either wild-type transhyretin (TTR) or hereditary transthyretin (TTR) genotype as per local standards.
- •Expected to be on stable doses of cardiovascular medical therapy 6 weeks prior to the randomisation visit.
- •Known end-diastolic interventricular septal wall thickness greater than or equal to (>=) 12 millimeters (mm).
- •Presently classified as New York Heart Association (NYHA) Class II-III.
- •N-terminal-pro brain natriuretic peptide (NT-proBNP) concentration greater than or equal to (>=) 650 picograms per milliliter (pg/mL) in sinus cardiac rhythm and greater than (>) 1000 pg/mL in atrial fibrillation at screening.
- •Completed greater than or equal to (>=) 150 meters to less than or equal to (<=) 450 meters on the 6-minute walk test (MWT) at screening.
- •Estimated glomerular filtration rate (eGFR) greater than or equal to (>=) 25 milliliter per minute per 1.73 meter square (mL/min/1.73 m^2) at screening.
排除标准
- •Cardiomyopathy not primarily caused by transthyretin amyloid cardiomyopathy transthyretin amyloid cardiomyopathy (ATTR CM), for example, cardiomyopathy due to hypertension, valvular heart disease, or ischemic heart disease.
- •A prior solid organ transplant.
- •Planned solid organ transplant during the study.
- •Presence or history of malignant neoplasm (other than basal or squamous cell skin cancer, insitu carcinomas of the cervix, or in-situ/high grade prostatic intraepithelial neoplasia (PIN) or low-grade prostate cancer) within 5 years before screening.
- •Current treatment with calcium channel blockers with conduction system effects (example [e.g.], verapamil, diltiazem). The use of dihydropyridine calcium channel blockers is allowed. The use of digoxin will only be allowed if required for management of atrial fibrillation with rapid ventricular response.
- •Acute coronary syndrome, unstable angina, stroke, transient ischemic attack (TIA), coronary revascularization, cardiac valve repair, or major surgery within 3 months of screening.
- •Body weight >120 kilogram (kg) (264.6 pounds [lb]) at screening.
- •History of contrast allergy or adverse reactions to gadolinium-containing agents.
研究组 & 干预措施
NNC6019-0001, Dose 2
Participants will receive dose 2 i.v. infusion of NNC6019-0001 Q4W added to standard of care until week 52.
干预措施: NNC6019-0001 (Drug)
Placebo
Participants will receive i.v. infusion of placebo (NNC6019-0001) Q4W added to standard of care until week 52.
干预措施: Placebo (NNC6019-0001) (Drug)
NNC6019-0001, Dose 1
Participants will receive dose 1 intravenous (i.v.) infusion of NNC6019-0001 every 4 weeks (Q4W) added to standard of care until week 52.
干预措施: NNC6019-0001 (Drug)
结局指标
主要结局
Change in N-terminal-pro brain natriuretic peptide (NT-proBNP)
时间窗: From baseline (week 0) to visit 15 (week 52)
Measured in Percentage
Change in 6-minute walk test (6-MWT)
时间窗: From baseline (week 0) to visit 15 (week 52)
Measured in Meters
次要结局
- Change in troponin I(From baseline (week 0) to visit 15 (week 52))
- Number of treatment emergent adverse events(From baseline (week 0) to visit 16 (week 64))
- Change in myocardial extracellular volume (ECV)(From baseline (week 0) to visit 15 (week 52))
- Number of cardiovascular (CV) events comprising hospitalisation due to CV events or urgent heart failure visits(From baseline (week 0) to visit 16 (week 64))
- Change in global longitudinal strain (GLS) on echocardiography(From baseline (week 0) to visit 15 (week 52))
- Time to occurrence of all-cause mortality(From baseline (week 0) to visit 16 (week 64))
- Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS)(From baseline (week 0) to visit 15 (week 52))
- Change in neuropathy impairment score (NIS)(From baseline (week 0) to visit 15 (week 52))