Clinical trial NCT04992065: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atherosclerotic Cardiovascular Disease
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2021-08-05
Enrollment: 267
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Percentage Change in Low-density Lipoprotein (LDL)-Cholesterol
timeFrame: Baseline (week 0), week 12
Secondary outcomes:
measure: Percentage Change in Total Cholesterol
timeFrame: Baseline (week 0), week 12
measure: Percentage Change in High Density Lipoprotein (HDL)-Cholesterol
timeFrame: Baseline (week 0), week 12
measure: Percentage Change in Very Low Density Lipoprotein (VLDL)-Cholesterol
timeFrame: Baseline (week 0), week 12
measure: Percentage Change in Triglycerides
timeFrame: Baseline (week 0), week 12
measure: Percentage Change in Total Apolipoprotein B (Apo B)
timeFrame: Baseline (week 0), week 12
measure: Percentage Change in Total Apolipoprotein CIII (Apo CIII)
timeFrame: Baseline (week 0), week 12
measure: Change in Total Lipoprotein(a) (Lp[a]): Ratio to Baseline
timeFrame: Baseline (week 0), week 12
measure: Number of Treatment-emergent Adverse Events (TEAEs)
timeFrame: From baseline (week 0) to 138 days
Other outcomes:
Locations:
city: Palm Springs
country: United States
facility: Desert Oasis Hlthcr Med Group
state: California
city: Boca Raton
country: United States
facility: Excel Med Ctr Clinical Trials
state: Florida
city: Fort Lauderdale
country: United States
facility: Integrative Research Associates, Inc
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Ctr For Clin Res
state: Florida
city: Arlington Heights
country: United States
facility: Northwest Heart Clin. Res.
state: Illinois
city: Covington
country: United States
facility: Louisiana Heart Center
state: Louisiana
city: Slidell
country: United States
facility: Louisiana Heart Center_Slidell
state: Louisiana
city: Omaha
country: United States
facility: VA NEB - Western IA Health Stm
state: Nebraska
city: Omaha
country: United States
facility: Univ of Nebraska Medical CTR
state: Nebraska
city: Albany
country: United States
facility: Albany Medical College - Endo
state: New York
city: West Seneca
country: United States
facility: Southgate Medical Group, LLP
state: New York
city: Dallas
country: United States
facility: Thyroid, Endocrinology, and Diabetes, PA
state: Texas
city: Houston
country: United States
facility: PlanIt Research, PLLC
state: Texas
city: Aalst
country: Belgium
facility: Algemeen Stedelijk Ziekenhuis - Aalst - Interventional Cardiology
city: Brugge
country: Belgium
facility: AZ Sint-Jan - Campus Brugge
city: Genk
country: Belgium
facility: Ziekenhuis Oost-Limburg AV - Cardiology
city: Haine-Saint-Paul
country: Belgium
facility: Hôpital de Jolimont_Haine-Saint-Paul_0
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis - Hasselt - Cardiology
city: Frankfurt
country: Germany
facility: MVZ CCB Frankfurt Und Main-Taunus GbR
city: Freiburg
country: Germany
facility: Medical Center - University Of Freiburg
city: München
country: Germany
facility: Deutsches Herzzentrum München - Klinik für Herz- und Kreislauferkrankungen
city: Villingen-Schwenningen
country: Germany
facility: Jacob, Villingen-Schwenningen
city: Athens
country: Greece
facility: "Sotiria" Thoracic Diseases Hospital of Athens
city: Athens
country: Greece
facility: Alexandra General Hospital, Therapeutic Clinic
city: Athens
country: Greece
facility: Konstantopouleio G.H. of Athens, "Agia Olga"
city: Athens
country: Greece
facility: "Hygeia" General Hospital of Athens
city: Chaidari, Athens
country: Greece
facility: U.G.H of Athens "Attikon"
city: Chios
country: Greece
facility: General Hospital of Chios "Skilitsio"
city: Saitama-shi, Saitama
country: Japan
facility: Sanai Hospital
city: Sendai-shi, Miyagi
country: Japan
facility: Shinden Higashi Clinic
city: Soka-shi, Saitama
country: Japan
facility: Soka Sugiura Internal Medicine Clinic
city: Tokyo
country: Japan
facility: Minamino Cardiovascular Hospital
city: Den Bosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis
city: Deventer
country: Netherlands
facility: Deventer Ziekenhuis
city: Groningen
country: Netherlands
facility: Martini Ziekenhuis
city: Haarlem
country: Netherlands
facility: Spaarne Gasthuis
city: Nijmegen
country: Netherlands
facility: Canisius-Wilhelmina Ziekenhuis
city: Sneek
country: Netherlands
facility: D & A Research B.V.
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Lubin
country: Poland
facility: Regionalny Osrodek Kardiologii
city: Swidnik
country: Poland
facility: Lubelskie Centrum Diagnostyczne Tomasz Blicharski
city: Warszawa
country: Poland
facility: Uniwersyteckie Centrum Kliniczne WUM
city: Warszawa
country: Poland
facility: Szpital Grochowski im. dr med. Rafała Masztaka Sp. z o.o.
city: Warszawa
country: Poland
facility: Narodowy Instytut Kardiologii Stefana kardynała Wyszynskiego
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (dept. 1452)
role: STUDY_DIRECTOR
References:
citation: 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.