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

Phase 2

Completed

Conditions: Atherosclerotic Cardiovascular Disease

Interventions: Drug: NNC0385-0434 A 15 mg
Other: Placebo I A (for NNC0385-0434 A 40 mg)
Drug: Evolocumab 140 mg/mL, Repatha®
Other: Placebo I A (for NNC0385-0434 A 15 mg)
Drug: NNC0385-0434 A 40 mg
Drug: NNC0385-0434 A 100 mg
Other: Placebo II A (for NNC0385-0434 A 100 mg)

Registration Number: NCT04992065

Lead Sponsor: Novo Nordisk A/S

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 267

Inclusion Criteria

Males or females of non-childbearing potential.
Established atherosclerotic cardiovascular disease (ASCVD) (criteria a) or ASCVD risk (criteria b):
1. Age 40 years or older at the time of signing informed consent and history of ASCVD
2. 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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Oral NNC0385-0434 15 mg once-daily (OD)	NNC0385-0434 A 15 mg	15 mg NNC0385-0434 co-formulated with 500 mg Salcaprozate sodium (SNAC) tablet once daily
Oral placebo (NNC0385-0434 40 mg)	Placebo I A (for NNC0385-0434 A 40 mg)	placebo administered as tablets (without SNAC) once daily
Subcutaneous evolocumab 140 mg Q2W	Evolocumab 140 mg/mL, Repatha®	140 mg evolocumab Subcutaneous (s.c.) injections every 2 weeks (51 participants). The s.c. evolocumab arm is open-label to limit unnecessary injections
Oral placebo (NNC0385-0434 15 mg)	Placebo I A (for NNC0385-0434 A 15 mg)	15 MG placebo administered as tablets (without SNAC) once daily
Oral NNC0385-0434 40 mg OD	NNC0385-0434 A 40 mg	40 mg study drug co-formulated with 500 mg SNAC tablet once daily
Oral NNC0385-0434 100 mg	NNC0385-0434 A 100 mg	100 mg NNC0385-0434 co-formulated with 500 mg SNAC tablet once daily (51 participants)
Oral placebo (NNC0385-0434 100 mg)	Placebo II A (for NNC0385-0434 A 100 mg)	placebo administered as tablets (without SNAC) once daily

Primary Outcome Measures

Name	Time	Method
Percentage Change in Low-density Lipoprotein (LDL)-Cholesterol	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 Outcome Measures

Name	Time	Method
Percentage Change in Total Cholesterol	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.
Percentage Change in Total Apolipoprotein B (Apo B)	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.
Percentage Change in Total Apolipoprotein CIII (Apo CIII)	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.
Percentage Change in High Density Lipoprotein (HDL)-Cholesterol	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.
Percentage Change in Very Low Density Lipoprotein (VLDL)-Cholesterol	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.
Percentage Change in Triglycerides	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.
Change in Total Lipoprotein(a) (Lp[a]): Ratio to Baseline	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.
Number of Treatment-emergent Adverse Events (TEAEs)	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.

Trial Locations

Locations (44): Northwest Heart Clin. Res.
🇺🇸
Arlington Heights, Illinois, United States
AZ Sint-Jan - Campus Brugge
🇧🇪
Brugge, Belgium
Deutsches Herzzentrum München - Klinik für Herz- und Kreislauferkrankungen
🇩🇪
München, Germany
Desert Oasis Hlthcr Med Group
🇺🇸
Palm Springs, California, United States
Excel Med Ctr Clinical Trials
🇺🇸
Boca Raton, Florida, United States
Integrative Research Associates, Inc
🇺🇸
Fort Lauderdale, Florida, United States
Jacksonville Ctr For Clin Res
🇺🇸
Jacksonville, Florida, United States
Louisiana Heart Center
🇺🇸
Covington, Louisiana, United States
Louisiana Heart Center_Slidell
🇺🇸
Slidell, Louisiana, United States
VA NEB - Western IA Health Stm
🇺🇸
Omaha, Nebraska, United States
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Northwest Heart Clin. Res.
🇺🇸Arlington Heights, Illinois, United States