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: 255

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
Change in low-density lipoprotein (LDL)-cholesterol	From baseline (week 0) to visit 9 (week 12)	percent

Secondary Outcome Measures

Name	Time	Method
Change in total cholesterol	From baseline (week 0) to visit 9 (week 12)	Percent
Change in high density lipoprotein (HDL)-cholesterol	From baseline (week 0) to visit 9 (week 12)	percent
Change in total Lipoprotein(a) ( Lp(a))	From baseline (week 0) to visit 9 (week 12)	Ratio
Treatment-emergent adverse events	From baseline (week 0) to visit 10 (19 weeks + 4 days)	Number of events
Change in very low density lipoprotein (VLDL)-cholesterol	From baseline (week 0) to visit 9 (week 12)	Percent
Change in triglycerides	From baseline (week 0) to visit 9 (week 12)	percent
Change in total Apo B	From baseline (week 0) to visit 9 (week 12)	percent
Change in total Apo CIII	From baseline (week 0) to visit 9 (week 12)	precent

Trial Locations

Locations (44): Northwest Heart Clinical Research, LLC
🇺🇸
Arlington Heights, Illinois, United States
Deventer Ziekenhuis
🇳🇱
Deventer, Netherlands
MVZ CCB Frankfurt Und Main-Taunus GbR
🇩🇪
Frankfurt, Germany
Medical Center - University Of Freiburg
🇩🇪
Freiburg, Germany
Shinden Higashi Clinic
🇯🇵
Sendai-shi, Miyagi, Japan
Jeroen Bosch Ziekenhuis
🇳🇱
Den Bosch, Netherlands
Uniwersyteckie Centrum Kliniczne
🇵🇱
Gdansk, Poland
"Hygeia" General Hospital of Athens
🇬🇷
Athens, Greece
Soka Sugiura Internal Medicine Clinic
🇯🇵
Soka-shi, Saitama, Japan
D & A Research B.V.
🇳🇱
Sneek, Netherlands
Uniwersyteckie Centrum Kliniczne WUM
🇵🇱
Warszawa, Poland
Minamino Cardiovascular Hospital
🇯🇵
Tokyo, Japan
Regionalny Osrodek Kardiologii
🇵🇱
Lubin, Poland
Lubelskie Centrum Diagnostyczne Tomasz Blicharski
🇵🇱
Swidnik, Poland
Szpital Grochowski im. dr med. Rafała Masztaka Sp. z o.o.
🇵🇱
Warszawa, Poland
Narodowy Instytut Kardiologii Stefana kardynała Wyszynskiego
🇵🇱
Warszawa, Poland
PlanIt Research, PLLC
🇺🇸
Houston, Texas, United States
Excel Med Ctr Clinical Trials
🇺🇸
Boca Raton, Florida, United States
Jacksonville Ctr For Clin Res
🇺🇸
Jacksonville, Florida, United States
Deutsches Herzzentrum München
🇩🇪
München, Germany
Louisiana Heart Center
🇺🇸
Hammond, Louisiana, United States
"Sotiria" Thoracic Diseases Hospital of Athens
🇬🇷
Athens, Greece
Spaarne Gasthuis
🇳🇱
Haarlem, Netherlands
Canisius-Wilhelmina Ziekenhuis
🇳🇱
Nijmegen, Netherlands
Albany Medical College - Endo
🇺🇸
Albany, New York, United States
Thyroid, Endocrinology, and Diabetes, PA
🇺🇸
Dallas, Texas, United States
Southgate Medical Group, LLP
🇺🇸
West Seneca, New York, United States
Alexandra General Hospital, Therapeutic Clinic
🇬🇷
Athens, Greece
Konstantopouleio G.H. of Athens, "Agia Olga"
🇬🇷
Athens, Greece
Martini Ziekenhuis
🇳🇱
Groningen, Netherlands
Algemeen Stedelijk Ziekenhuis - Aalst - Interventional Cardiology
🇧🇪
Aalst, Belgium
AZ Sint-Jan - Campus Brugge_Brugge
🇧🇪
Brugge, Belgium
Ziekenhuis Oost-Limburg AV - Cardiology
🇧🇪
Genk, Belgium
Hôpital de Jolimont_Haine-Saint-Paul_0
🇧🇪
Haine-Saint-Paul, Belgium
Jessa Ziekenhuis - Hasselt - Cardiology
🇧🇪
Hasselt, Belgium
Jacob, Villingen-Schwenningen
🇩🇪
Villingen-Schwenningen, Germany
Integrative Research Associates, Inc
🇺🇸
Fort Lauderdale, Florida, United States
U.G.H of Athens "Attikon"
🇬🇷
Chaidari, Athens, Greece
General Hospital of Chios "Skilitsio"
🇬🇷
Chios, Greece
Sanai Hospital
🇯🇵
Saitama-shi, Saitama, Japan
Louisiana Heart Center_Slidell
🇺🇸
Slidell, Louisiana, United States
VA NEB - Western IA Health Stm
🇺🇸
Omaha, Nebraska, United States
Univ of Nebraska Medical CTR
🇺🇸
Omaha, Nebraska, United States
Desert Oasis Hlthcr Med Group
🇺🇸
Palm Springs, California, United States