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

NCT04992065 | Completed Phase 2 Results FDA Drug

• 4 other identifiers: NN6435-4697U1111-1252-33922020-002630-32151409
• Study Type: interventional
• Target: 267
• Locations: 7 countries
• Sites: 44

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

Outcome Measures

Primary Outcomes (1)

• Percentage Change in Low-density Lipoprotein (LDL)-Cholesterol

  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.

  Baseline (week 0), week 12

Secondary Outcomes (8)

• Percentage Change in Total Cholesterol

  Baseline (week 0), week 12

• Percentage Change in High Density Lipoprotein (HDL)-Cholesterol

  Baseline (week 0), week 12

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

  Baseline (week 0), week 12

• Percentage Change in Triglycerides

  Baseline (week 0), week 12

• Percentage Change in Total Apolipoprotein B (Apo B)

  Baseline (week 0), week 12

Study Arms (7)

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

EXPERIMENTAL

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

Drug: NNC0385-0434 A 15 mg

Oral placebo (NNC0385-0434 15 mg)

PLACEBO COMPARATOR

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

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

Oral NNC0385-0434 40 mg OD

EXPERIMENTAL

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

Drug: NNC0385-0434 A 40 mg

Oral placebo (NNC0385-0434 40 mg)

PLACEBO COMPARATOR

placebo administered as tablets (without SNAC) once daily

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

Oral NNC0385-0434 100 mg

EXPERIMENTAL

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

Drug: NNC0385-0434 A 100 mg

Oral placebo (NNC0385-0434 100 mg)

PLACEBO COMPARATOR

placebo administered as tablets (without SNAC) once daily

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

Subcutaneous evolocumab 140 mg Q2W

ACTIVE COMPARATOR

140 mg evolocumab Subcutaneous (s.c.) injections every 2 weeks (51 participants). The s.c. evolocumab arm is open-label to limit unnecessary injections

Drug: Evolocumab 140 mg/mL, Repatha®

Interventions

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).

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

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).

Oral NNC0385-0434 40 mg OD

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

Oral placebo (NNC0385-0434 15 mg)

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).

Oral NNC0385-0434 100 mg

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

Oral placebo (NNC0385-0434 40 mg)

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

Oral placebo (NNC0385-0434 100 mg)

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

Subcutaneous evolocumab 140 mg Q2W

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novo Nordisk A/S: lead

Study Sites (44)

Desert Oasis Hlthcr Med Group

Palm Springs, California, 92262, United States

Location

Excel Med Ctr Clinical Trials

Boca Raton, Florida, 33434, United States

Location

Integrative Research Associates, Inc

Fort Lauderdale, Florida, 33312, United States

Location

Jacksonville Ctr For Clin Res

Jacksonville, Florida, 32216, United States

Location

Northwest Heart Clin. Res.

Arlington Heights, Illinois, 60005, United States

Location

Louisiana Heart Center

Covington, Louisiana, 70433, United States

Location

Louisiana Heart Center_Slidell

Slidell, Louisiana, 70458, United States

Location

VA NEB - Western IA Health Stm

Omaha, Nebraska, 68105, United States

Location

Univ of Nebraska Medical CTR

Omaha, Nebraska, 68198, United States

Location

Albany Medical College - Endo

Albany, New York, 12203, United States

Location

Southgate Medical Group, LLP

West Seneca, New York, 14224, United States

Location

Thyroid, Endocrinology, and Diabetes, PA

Dallas, Texas, 75208, United States

Location

PlanIt Research, PLLC

Houston, Texas, 77079, United States

Location

Algemeen Stedelijk Ziekenhuis - Aalst - Interventional Cardiology

Aalst, 9300, Belgium

Location

AZ Sint-Jan - Campus Brugge

Bruges, 8000, Belgium

Location

Ziekenhuis Oost-Limburg AV - Cardiology

Genk, 3600, Belgium

Location

Hôpital de Jolimont_Haine-Saint-Paul_0

Haine-Saint-Paul, 7100, Belgium

Location

Jessa Ziekenhuis - Hasselt - Cardiology

Hasselt, 3500, Belgium

Location

MVZ CCB Frankfurt Und Main-Taunus GbR

Frankfurt, 60389, Germany

Location

Medical Center - University Of Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Deutsches Herzzentrum München - Klinik für Herz- und Kreislauferkrankungen

München, 80636, Germany

Location

Jacob, Villingen-Schwenningen

Villingen-Schwenningen, 78048, Germany

Location

"Sotiria" Thoracic Diseases Hospital of Athens

Athens, 11527, Greece

Location

Alexandra General Hospital, Therapeutic Clinic

Athens, 11528, Greece

Location

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

Athens, 14233, Greece

Location

"Hygeia" General Hospital of Athens

Athens, 15123, Greece

Location

U.G.H of Athens "Attikon"

Chaidari, Athens, 12462, Greece

Location

General Hospital of Chios "Skilitsio"

Chios, 82100, Greece

Location

Sanai Hospital

Saitama-shi, Saitama, 338-0837, Japan

Location

Shinden Higashi Clinic

Sendai-shi, Miyagi, 983-0039, Japan

Location

Soka Sugiura Internal Medicine Clinic

Soka-shi, Saitama, 340-0015, Japan

Location

Minamino Cardiovascular Hospital

Tokyo, 192-0918, Japan

Location

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, 5223 GZ, Netherlands

Location

Deventer Ziekenhuis

Deventer, 7416 SE, Netherlands

Location

Martini Ziekenhuis

Groningen, 9728 NT, Netherlands

Location

Spaarne Gasthuis

Haarlem, 2035 RC, Netherlands

Location

Canisius-Wilhelmina Ziekenhuis

Nijmegen, 6532 SZ, Netherlands

Location

D & A Research B.V.

Sneek, 8601 ZR, Netherlands

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-952, Poland

Location

Regionalny Osrodek Kardiologii

Lubin, 59-301, Poland

Location

Lubelskie Centrum Diagnostyczne Tomasz Blicharski

Świdnik, 21-040, Poland

Location

Uniwersyteckie Centrum Kliniczne WUM

Warsaw, 02-097, Poland

Location

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

Warsaw, 04-073, Poland

Location

Narodowy Instytut Kardiologii Stefana kardynała Wyszynskiego

Warsaw, 04-628, Poland

Location

Related Publications (1)

• 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.

  PMID: 38310920 RESULT

MeSH Terms

Conditions

Atherosclerosis

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Clinical Reporting Office (2834)
• Organization: Novo Nordisk A/S

clinicaltrials@novonordisk.com

(+1) 866-867-7178

Study Officials

• Clinical Transparency (dept. 1452)

  Novo Nordisk A/S

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: The trial will be double-blinded within dose level of oral NNC0385-0434 and size-matched placebo arm. The subcutaneous (s.c.) evolocumab arm will be open label.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2021
• First Posted: August 5, 2021
• Study Start: August 3, 2021
• Primary Completion: April 26, 2022
• Study Completion: June 20, 2022
• Last Updated: June 8, 2025
• Results First Posted: June 8, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share

Locations

JP (4); US (13); BE (5); DE (4); GR (6); NL (6); PL (6)