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 reductio

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 45

Inclusion Criteria

- Male patient or female patient of non-childbearing potential.
- Established atherosclerotic cardiovascular disease (ASCVD) (criteria a) or
ASCVD risk (criteria b):
a)Age greater than or equal to 40 years at the time of signing informed consent
and history of ASCVD
b)Age greater than 50 years at the time of signing informed consent and with
ASCVD risk
- Serum LDL-C greater than or equal to1.8 mmol/L (greater than or equal to 70
mg/dL) as measured by the central laboratory at screening.
Japanese patients: Serum LDL-C greater than or equal to 2.6 mmol/L (greater
than or equal to 100 mg/dL) for patients of greater than or equal to 40 years
of age and with a history of coronary heart disease, and serum LDL-C greater
than or equal to 3.1 mmol/L (greater than or equal to 120 mg/dL) for all other
Japanese patients
- Patients must be on maximally tolerated dose of statins.
- Patients not receiving statin must have documented evidence of intolerance to
all doses of at least two different statins.

Exclusion Criteria

- 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 greater than 4.52 mmol/L (greater than 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 below 30 ml/min/1.73 m^2 as measured by the
central laboratory at screening.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Change in LDL-cholesterol From baseline (week 0) to visit 9 (week 12) %</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Supportive secondary endpoints<br /><br>% Change in total cholesterol From baseline (week 0) to visit 9 (week 12)<br /><br>% Change in HDL-cholesterol From baseline (week 0) to visit 9 (week 12)<br /><br>% Change in VLDL-cholesterol From baseline (week 0) to visit 9 (week 12)<br /><br>% Change in triglycerides From baseline (week 0) to visit 9 (week 12)<br /><br>% Change in total Apo B From baseline (week 0) to visit 9 (week 12)<br /><br>% Change in total Apo CIII From baseline (week 0) to visit 9 (week 12)<br /><br>Ratio Change in total Lp(a) From baseline (week 0) to visit 9 (week 12)<br /><br>Number of adverse events: Treatment-emergent adverse events From baseline (week<br /><br>0) to visit 10 (19 weeks + 4 days)<br /><br>Number of events</p><br>