Dose Response and Safety of an Oral PCSK9i, NNC0385-0434, in Patients With Established Atherosclerotic Cardiovascular Disease (ASCVD) or ASCVD Risk on Maximally Tolerated Statin Dose and Other Lipid-lowering Therapy Requiring Further LDL-C Reduction
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 267
- 试验地点
- 44
- 主要终点
- Percentage Change in Low-density Lipoprotein (LDL)-Cholesterol
研究概览
简要总结
This study looks at how well a new medicine, NNC0385-0434, works to lower blood cholesterol levels. Participants will either get NNC0385-0434 as a tablet (a potential new medicine), or placebo as a tablet (a dummy medicine that looks like NNC0385-0434 but has no effect on the body), or evolocumab as an injection (a medicine that doctors can already prescribe).
Which treatment participants get is decided by chance. If participants get NNC0385-0434 or placebo participants will need to take 1 tablet every morning. If participants get evolocumab participants will need to take 1 injection every 2 weeks.
The study will last for about 22 weeks. About 255 people will participate in the study. Participants will have 9 visits to the clinic and 2 phone calls with the study doctor. Some people will be invited to participate in a sub-study and will have 4 extra visits (13 visits in total). Participants will have blood samples taken at all visits to the clinic (except visit 0). At 4 clinic visits, participants will have an electrocardiogram (ECG). This is a test to check your heart.
Women can only take part in the study if they are not able to become pregnant.
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
- Double (Participant, Care Provider)
盲法说明
The trial will be double-blinded within dose level of oral NNC0385-0434 and size-matched placebo arm. The subcutaneous (s.c.) evolocumab arm will be open label.
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females of non-childbearing potential.
- •Established atherosclerotic cardiovascular disease (ASCVD) (criteria a) or ASCVD risk (criteria b):
- •Age 40 years or older at the time of signing informed consent and history of ASCVD
- •Age above 50 years at the time of signing informed consent and with ASCVD risk
- •Serum LDL-C above or equal to 1.8 mmol/L (above or equal to 70 mg/dL) as measured by the central laboratory at screening.
- •Japanese participants: Serum LDL-C above or equal to 2.6 mmol/L (above or equal to 100 mg/dL) for participants of 40 years of age or older and with a history of coronary heart disease, and serum LDL-C above or equal to 3.1 mmol/L (above or equal to 120 mg/dL) for all other Japanese participants
- •Participants must be on maximally tolerated dose of statins.
- •Participants not receiving statin must have documented evidence of intolerance to all doses of at least two different statins.
排除标准
- •Treatment with PCSK9i therapy (alirocumab or evolocumab within 90 days prior to screening) or PCSK9 siRNA therapy (inclisiran within 12 months prior to screening).
- •Fasting triglyceride above 4.52 mmol/L (above 400 mg/dL) as measured by the central laboratory at screening.
- •Myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within 180 days prior to the day of screening.
- •Renal impairment with eGFR less than 30 ml/min/1.73 m2 as measured by the central laboratory at screening
研究组 & 干预措施
Oral NNC0385-0434 40 mg OD
40 mg study drug co-formulated with 500 mg SNAC tablet once daily
干预措施: NNC0385-0434 A 40 mg (Drug)
Oral NNC0385-0434 15 mg once-daily (OD)
15 mg NNC0385-0434 co-formulated with 500 mg Salcaprozate sodium (SNAC) tablet once daily
干预措施: NNC0385-0434 A 15 mg (Drug)
Oral placebo (NNC0385-0434 15 mg)
15 MG placebo administered as tablets (without SNAC) once daily
干预措施: Placebo I A (for NNC0385-0434 A 15 mg) (Other)
Oral placebo (NNC0385-0434 40 mg)
placebo administered as tablets (without SNAC) once daily
干预措施: Placebo I A (for NNC0385-0434 A 40 mg) (Other)
Oral NNC0385-0434 100 mg
100 mg NNC0385-0434 co-formulated with 500 mg SNAC tablet once daily (51 participants)
干预措施: NNC0385-0434 A 100 mg (Drug)
Oral placebo (NNC0385-0434 100 mg)
placebo administered as tablets (without SNAC) once daily
干预措施: Placebo II A (for NNC0385-0434 A 100 mg) (Other)
Subcutaneous evolocumab 140 mg Q2W
140 mg evolocumab Subcutaneous (s.c.) injections every 2 weeks (51 participants). The s.c. evolocumab arm is open-label to limit unnecessary injections
干预措施: Evolocumab 140 mg/mL, Repatha® (Drug)
结局指标
主要结局
Percentage Change in Low-density Lipoprotein (LDL)-Cholesterol
时间窗: Baseline (week 0), week 12
Percentage change in LDL-cholesterol (LDL-C) (measured in milligrams per deciliter \[mg/dL\]) at week 12 is presented. Data is reported for the on-treatment period. The on-treatment period is the time period where participants were considered exposed to trial product. The observation period starts at the date of first dose of trial product and ends at the first date of any of the following: The follow-up visit or the last date on randomised treatment regimen + 58 days or the end-date for the 'in-trial' observation period. The in-trial period is defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site.
次要结局
- Percentage Change in Total Cholesterol(Baseline (week 0), week 12)
- Percentage Change in High Density Lipoprotein (HDL)-Cholesterol(Baseline (week 0), week 12)
- Percentage Change in Very Low Density Lipoprotein (VLDL)-Cholesterol(Baseline (week 0), week 12)
- Percentage Change in Triglycerides(Baseline (week 0), week 12)
- Percentage Change in Total Apolipoprotein B (Apo B)(Baseline (week 0), week 12)
- Percentage Change in Total Apolipoprotein CIII (Apo CIII)(Baseline (week 0), week 12)
- Change in Total Lipoprotein(a) (Lp[a]): Ratio to Baseline(Baseline (week 0), week 12)
- Number of Treatment-emergent Adverse Events (TEAEs)(From baseline (week 0) to 138 days)