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Completed

NCT Number: NCT04992065

A Research Study Looking at How NNC0385-0434 Tablets Work to Lower Blood Cholesterol in People With Heart Disease or a High Risk of Heart Disease

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.

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Key information

Conditions

Atherosclerotic Cardiovascular Disease Arterial Occlusive Diseases Arteriosclerosis Atherosclerosis Cardiovascular Diseases Vascular Diseases

Age range

40 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Algemeen Stedelijk Ziekenhuis - Aalst - Interventional Cardiology, Aalst, Belgium

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

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 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

Treatment and study plan

NNC0385-0434 A 15 mg

Drug

15 mg administered as one oral tablet once daily in the morning in a fasting state. The tablet should be taken at least 30 min before the first food, beverage or other oral medications of the day. The tablet can be taken with up to half a glass of water (approximately 120 mL/ 4 fluid ounces).

NNC0385-0434 A 40 mg

Drug

40 mg administered as one oral tablet once daily in the morning in a fasting state. The tablet should be taken at least 30 min before the first food, beverage or other oral medications of the day. The tablet can be taken with up to half a glass of water (approximately 120 mL/ 4 fluid ounces).

Placebo I A (for NNC0385-0434 A 15 mg)

Other

Placebo administered as 1 tablet once daily in the morning in a fasting state. The tablet should be taken at least 30 min before the first food, beverage or other oral medications of the day. The tablet can be taken with up to half a glass of water (approximately 120 mL/ 4 fluid ounces). placebo tablets are sized match to the active arm within dose level

NNC0385-0434 A 100 mg

Drug

100 mg administered as one oral tablet once daily in the morning in a fasting state.

The tablet should be taken at least 30 min before the first food, beverage or other oral medications of the day.

The tablet can be taken with up to half a glass of water (approximately 120 mL/ 4 fluid ounces).

Placebo I A (for NNC0385-0434 A 40 mg)

Other

Placebo administered as one tablet once daily in the morning in a fasting state.

The tablet should be taken at least 30 min before the first food, beverage or other oral medications of the day.

The tablet can be taken with up to half a glass of water (approximately 120 mL/ 4 fluid ounces).

placebo tablets are sized match to the active arm within dose level

Placebo II A (for NNC0385-0434 A 100 mg)

Other

Placebo administered as one tablet once daily in the morning in a fasting state.

The tablet should be taken at least 30 min before the first food, beverage or other oral medications of the day.

The tablet can be taken with up to half a glass of water (approximately 120 mL/ 4 fluid ounces).

placebo tablets are sized match to the active arm within dose level

Evolocumab 140 mg/mL, Repatha®

Drug

Every 2 weeks subcutaneous (s.c.) injection of 140 mg into areas of the abdomen, thigh, or upper arm that are not tender, bruised, red, or indurated. Administered using a pre-filled SureClick® autoinjector (single-use).

Dose volume: 1 mL

Primary outcomes

  1. Percentage Change in Low-density Lipoprotein (LDL)-Cholesterol

    Time frame: 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.

Secondary outcomes

  1. Percentage Change in Total Cholesterol

    Time frame: Baseline (week 0), week 12

    Percentage change in total cholesterol (measured in millimoles per iliter [mmol/L]) 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.

  2. Percentage Change in High Density Lipoprotein (HDL)-Cholesterol

    Time frame: Baseline (week 0), week 12

    Percentage change in HDL-cholesterol (measured in 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.

  3. Percentage Change in Very Low Density Lipoprotein (VLDL)-Cholesterol

    Time frame: Baseline (week 0), week 12

    Percentage change in VLDL-cholesterol (measured in mmol/L) 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.

  4. Percentage Change in Triglycerides

    Time frame: Baseline (week 0), week 12

    Percentage change in triglycerides (measured in 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.

  5. Percentage Change in Total Apolipoprotein B (Apo B)

    Time frame: Baseline (week 0), week 12

    Percentage change in Apo B (measured in 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.

  6. Percentage Change in Total Apolipoprotein CIII (Apo CIII)

    Time frame: Baseline (week 0), week 12

    Percentage change in Apo CIII (measured in 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.

  7. Change in Total Lipoprotein(a) (Lp[a]): Ratio to Baseline

    Time frame: Baseline (week 0), week 12

    Change in total Lp(a) (measured in mg/dL) at week 12 is presented as ratio to baseline. 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.

  8. Number of Treatment-emergent Adverse Events (TEAEs)

    Time frame: From baseline (week 0) to 138 days

    An adverse events (AE) is any untoward medical occurrence in a clinical trial participant that is temporally associated with the use of an investigational medicinal product (IMP), whether or not considered related to the IMP. All presented AEs are TEAEs. TEAEs was the number of AEs recorded during 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.

Sponsors and collaborators

Lead sponsor

Novo Nordisk A/S

Industry

Registry information

Official study title

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

Important dates

Study start
2021
Primary completion
2022
Study completion
2022
First posted
Aug 5, 2021
Registry last updated
Jun 8, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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