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

Atherosclerotic Cardiovascular Disease Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04992065
• Other study ID #: NN6435-4697
• Secondary ID: U1111-1252-33922
• Status: Completed
• Phase: Phase 2
• Start date: August 3, 2021
• Est. completion date: June 20, 2022

Study information

• Verified date: February 2024
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 255
• Est. completion date: June 20, 2022
• Est. primary completion date: April 26, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atherosclerosis
• Atherosclerotic Cardiovascular Disease
• Cardiovascular Diseases

Intervention

Drug:
• 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).
• 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).

Other:
• 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

Drug:
• 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).

Other:
• 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
• 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

Drug:
• 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

Locations

Country	Name	City	State
Belgium	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
Germany	MVZ CCB Frankfurt Und Main-Taunus GbR	Frankfurt
Germany	Medical Center - University Of Freiburg	Freiburg
Germany	Deutsches Herzzentrum München	München
Germany	Jacob, Villingen-Schwenningen	Villingen-Schwenningen
Greece	"Hygeia" General Hospital of Athens	Athens
Greece	"Sotiria" Thoracic Diseases Hospital of Athens	Athens
Greece	Alexandra General Hospital, Therapeutic Clinic	Athens
Greece	Konstantopouleio G.H. of Athens, "Agia Olga"	Athens
Greece	U.G.H of Athens "Attikon"	Chaidari, Athens
Greece	General Hospital of Chios "Skilitsio"	Chios
Japan	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
Netherlands	Jeroen Bosch Ziekenhuis	Den Bosch
Netherlands	Deventer Ziekenhuis	Deventer
Netherlands	Martini Ziekenhuis	Groningen
Netherlands	Spaarne Gasthuis	Haarlem
Netherlands	Canisius-Wilhelmina Ziekenhuis	Nijmegen
Netherlands	D & A Research B.V.	Sneek
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Regionalny Osrodek Kardiologii	Lubin
Poland	Lubelskie Centrum Diagnostyczne Tomasz Blicharski	Swidnik
Poland	Narodowy Instytut Kardiologii Stefana kardynala Wyszynskiego	Warszawa
Poland	Szpital Grochowski im. dr med. Rafala Masztaka Sp. z o.o.	Warszawa
Poland	Uniwersyteckie Centrum Kliniczne WUM	Warszawa
United States	Albany Medical College - Endo	Albany	New York
United States	Northwest Heart Clinical Research, LLC	Arlington Heights	Illinois
United States	Excel Med Ctr Clinical Trials	Boca Raton	Florida
United States	Thyroid, Endocrinology, and Diabetes, PA	Dallas	Texas
United States	Integrative Research Associates, Inc	Fort Lauderdale	Florida
United States	Louisiana Heart Center	Hammond	Louisiana
United States	PlanIt Research, PLLC	Houston	Texas
United States	Jacksonville Ctr For Clin Res	Jacksonville	Florida
United States	Univ of Nebraska Medical CTR	Omaha	Nebraska
United States	VA NEB - Western IA Health Stm	Omaha	Nebraska
United States	Desert Oasis Hlthcr Med Group	Palm Springs	California
United States	Louisiana Heart Center_Slidell	Slidell	Louisiana
United States	Southgate Medical Group, LLP	West Seneca	New York

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

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

References & 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, do — View Citation

Outcome

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