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

NCT ID: NCT04992065

Last Updated: 2025-06-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 267 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-03
• Study Completion Date: 2022-06-20

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.

Conditions

Atherosclerotic Cardiovascular Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Oral NNC0385-0434 15 mg once-daily (OD)

15 mg NNC0385-0434 co-formulated with 500 mg Salcaprozate sodium (SNAC) tablet once daily

Group Type: EXPERIMENTAL

NNC0385-0434 A 15 mg

Intervention Type: 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).

Oral placebo (NNC0385-0434 15 mg)

15 MG placebo administered as tablets (without SNAC) once daily

Group Type: PLACEBO_COMPARATOR

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

Intervention Type: 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

Oral NNC0385-0434 40 mg OD

40 mg study drug co-formulated with 500 mg SNAC tablet once daily

Group Type: EXPERIMENTAL

NNC0385-0434 A 40 mg

Intervention Type: 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).

Oral placebo (NNC0385-0434 40 mg)

placebo administered as tablets (without SNAC) once daily

Group Type: PLACEBO_COMPARATOR

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

Intervention Type: 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

Oral NNC0385-0434 100 mg

100 mg NNC0385-0434 co-formulated with 500 mg SNAC tablet once daily (51 participants)

Group Type: EXPERIMENTAL

NNC0385-0434 A 100 mg

Intervention Type: 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).

Oral placebo (NNC0385-0434 100 mg)

placebo administered as tablets (without SNAC) once daily

Group Type: PLACEBO_COMPARATOR

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

Intervention Type: 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

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

Group Type: ACTIVE_COMPARATOR

Evolocumab 140 mg/mL, Repatha®

Intervention Type: 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

Interventions

NNC0385-0434 A 15 mg

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).

Intervention Type: DRUG

NNC0385-0434 A 40 mg

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).

Intervention Type: DRUG

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

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

Intervention Type: OTHER

NNC0385-0434 A 100 mg

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).

Intervention Type: DRUG

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

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

Intervention Type: OTHER

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

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

Intervention Type: OTHER

Evolocumab 140 mg/mL, Repatha®

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novo Nordisk A/S

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Transparency (dept. 1452)

Role: STUDY_DIRECTOR

Novo Nordisk A/S

Locations

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

Northwest Heart Clin. Res.

Arlington Heights, Illinois, 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

Univ of Nebraska Medical CTR

Omaha, Nebraska, United States

Albany Medical College - Endo

Albany, New York, United States

Southgate Medical Group, LLP

West Seneca, New York, United States

Thyroid, Endocrinology, and Diabetes, PA

Dallas, Texas, United States

PlanIt Research, PLLC

Houston, Texas, United States

Algemeen Stedelijk Ziekenhuis - Aalst - Interventional Cardiology

Aalst, , Belgium

AZ Sint-Jan - Campus Brugge

Bruges, , 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

MVZ CCB Frankfurt Und Main-Taunus GbR

Frankfurt, , Germany

Medical Center - University Of Freiburg

Freiburg im Breisgau, , Germany

Deutsches Herzzentrum München - Klinik für Herz- und Kreislauferkrankungen

München, , Germany

Jacob, Villingen-Schwenningen

Villingen-Schwenningen, , Germany

"Sotiria" Thoracic Diseases Hospital of Athens

Athens, , Greece

Alexandra General Hospital, Therapeutic Clinic

Athens, , Greece

Konstantopouleio G.H. of Athens, "Agia Olga"

Athens, , Greece

"Hygeia" General Hospital of Athens

Athens, , Greece

U.G.H of Athens "Attikon"

Chaidari, Athens, , Greece

General Hospital of Chios "Skilitsio"

Chios, , Greece

Sanai Hospital

Saitama-shi, Saitama, , Japan

Shinden Higashi Clinic

Sendai-shi, Miyagi, , Japan

Soka Sugiura Internal Medicine Clinic

Soka-shi, Saitama, , Japan

Minamino Cardiovascular Hospital

Tokyo, , Japan

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, , Netherlands

Deventer Ziekenhuis

Deventer, , Netherlands

Martini Ziekenhuis

Groningen, , Netherlands

Spaarne Gasthuis

Haarlem, , Netherlands

Canisius-Wilhelmina Ziekenhuis

Nijmegen, , Netherlands

D & A Research B.V.

Sneek, , Netherlands

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Regionalny Osrodek Kardiologii

Lubin, , Poland

Lubelskie Centrum Diagnostyczne Tomasz Blicharski

Świdnik, , Poland

Uniwersyteckie Centrum Kliniczne WUM

Warsaw, , Poland

Szpital Grochowski im. dr med. Rafała Masztaka Sp. z o.o.

Warsaw, , Poland

Narodowy Instytut Kardiologii Stefana kardynała Wyszynskiego

Warsaw, , Poland

Countries

United States; Belgium; Germany; Greece; Japan; Netherlands; Poland

References

Koren MJ, Descamps O, Hata Y, Hengeveld EM, Hovingh GK, Ikonomidis I, Radu Juul Jensen MD, Langbakke IH, Martens FMAC, Sondergaard AL, Witkowski A, Koenig W. PCSK9 inhibition with orally administered NNC0385-0434 in hypercholesterolaemia: a randomised, double-blind, placebo-controlled and active-controlled phase 2 trial. Lancet Diabetes Endocrinol. 2024 Mar;12(3):174-183. doi: 10.1016/S2213-8587(23)00325-X. Epub 2024 Feb 1.

Reference Type: RESULT

PMID: 38310920 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1252-3392

Identifier Type: OTHER

Identifier Source: secondary_id

2020-002630-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

151409

Identifier Type: OTHER

Identifier Source: secondary_id

NN6435-4697

Identifier Type: -

Identifier Source: org_study_id