Atherosclerotic Cardiovascular DiseasePhase 2NCT04992065
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
A Phase 2 study testing NNC0385-0434 A 15 mg, NNC0385-0434 A 40 mg and NNC0385-0434 A 100 mg in people with Atherosclerotic Cardiovascular Disease, run by Novo Nordisk A/S at 44 sites in 7 countries.
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… Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Atherosclerotic Cardiovascular Disease
- What is being tested?
- NNC0385-0434 A 15 mg, NNC0385-0434 A 40 mg and NNC0385-0434 A 100 mg
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 267 participants
- Where
- 44 sitesin 7 countries
- Study dates
- 3 Aug 2021to 20 Jun 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
44 sites in 7 countries.
44 sites in 7 countries
United States13 sites
Albany Medical College - Endo
Albany, New York, 12203
Northwest Heart Clin. Res.
Arlington Heights, Illinois, 60005
Excel Med Ctr Clinical Trials
Boca Raton, Florida, 33434
Louisiana Heart Center
Covington, Louisiana, 70433
Thyroid, Endocrinology, and Diabetes, PA
Dallas, Texas, 75208
Integrative Research Associates, Inc
Fort Lauderdale, Florida, 33312
PlanIt Research, PLLC
Houston, Texas, 77079
Jacksonville Ctr For Clin Res
Jacksonville, Florida, 32216
VA NEB - Western IA Health Stm
Omaha, Nebraska, 68105
Univ of Nebraska Medical CTR
Omaha, Nebraska, 68198
Desert Oasis Hlthcr Med Group
Palm Springs, California, 92262
Louisiana Heart Center_Slidell
Slidell, Louisiana, 70458
Southgate Medical Group, LLP
West Seneca, New York, 14224
Greece6 sites
"Sotiria" Thoracic Diseases Hospital of Athens
Athens, 11527
Alexandra General Hospital, Therapeutic Clinic
Athens, 11528
Konstantopouleio G.H. of Athens, "Agia Olga"
Athens, 14233
"Hygeia" General Hospital of Athens
Athens, 15123
U.G.H of Athens "Attikon"
Chaidari, Athens, 12462
General Hospital of Chios "Skilitsio"
Chios, 82100
Netherlands6 sites
Jeroen Bosch Ziekenhuis
's-Hertogenbosch, 5223 GZ
Deventer Ziekenhuis
Deventer, 7416 SE
Martini Ziekenhuis
Groningen, 9728 NT
Spaarne Gasthuis
Haarlem, 2035 RC
Canisius-Wilhelmina Ziekenhuis
Nijmegen, 6532 SZ
D & A Research B.V.
Sneek, 8601 ZR
Poland6 sites
Uniwersyteckie Centrum Kliniczne
Gdansk, 80-952
Regionalny Osrodek Kardiologii
Lubin, 59-301
Lubelskie Centrum Diagnostyczne Tomasz Blicharski
Świdnik, 21-040
Uniwersyteckie Centrum Kliniczne WUM
Warsaw, 02-097
Szpital Grochowski im. dr med. Rafała Masztaka Sp. z o.o.
Warsaw, 04-073
Narodowy Instytut Kardiologii Stefana kardynała Wyszynskiego
Warsaw, 04-628
Belgium5 sites
Algemeen Stedelijk Ziekenhuis - Aalst - Interventional Cardiology
Aalst, 9300
AZ Sint-Jan - Campus Brugge
Bruges, 8000
Ziekenhuis Oost-Limburg AV - Cardiology
Genk, 3600
Hôpital de Jolimont_Haine-Saint-Paul_0
Haine-Saint-Paul, 7100
Jessa Ziekenhuis - Hasselt - Cardiology
Hasselt, 3500
Germany4 sites
MVZ CCB Frankfurt Und Main-Taunus GbR
Frankfurt, 60389
Medical Center - University Of Freiburg
Freiburg im Breisgau, 79106
Deutsches Herzzentrum München - Klinik für Herz- und Kreislauferkrankungen
München, 80636
Jacob, Villingen-Schwenningen
Villingen-Schwenningen, 78048
Japan4 sites
Sanai Hospital
Saitama-shi, Saitama, 338-0837
Shinden Higashi Clinic
Sendai-shi, Miyagi, 983-0039
Soka Sugiura Internal Medicine Clinic
Soka-shi, Saitama, 340-0015
Minamino Cardiovascular Hospital
Tokyo, 192-0918
About this study
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
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.
Read more
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
- Being tested
- NNC0385-0434 A 15 mg, NNC0385-0434 A 40 mg, Placebo I A (for NNC0385-0434 A 15 mg), NNC0385-0434 A 100 mg, Placebo I A (for NNC0385-0434 A 40 mg)
- Medical subject headings
- Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NNC0385-0434 A 15 mgDrug
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 mgDrug
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).
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
NNC0385-0434 A 100 mgDrug
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).
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
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
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
| Study group | Role | What they receive |
|---|---|---|
| Oral NNC0385-0434 15 mg once-daily (OD) | Experimental | 15 mg NNC0385-0434 co-formulated with 500 mg Salcaprozate sodium (SNAC) tablet once daily Receives: Drug: NNC0385-0434 A 15 mg |
| Oral placebo (NNC0385-0434 15 mg) | Placebo comparator | 15 MG placebo administered as tablets (without SNAC) once daily Receives: 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 Receives: Drug: NNC0385-0434 A 40 mg |
| Oral placebo (NNC0385-0434 40 mg) | Placebo comparator | placebo administered as tablets (without SNAC) once daily Receives: 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) Receives: Drug: NNC0385-0434 A 100 mg |
| Oral placebo (NNC0385-0434 100 mg) | Placebo comparator | placebo administered as tablets (without SNAC) once daily Receives: 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 Receives: Drug: Evolocumab 140 mg/mL, Repatha® |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline (week 0), week 12
Secondary outcomes (8)
Percentage Change in Total Cholesterol
Percentage change in total cholesterol (measured in millimoles per iliter [mmol/L]) 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.
Measured: Baseline (week 0), week 12
Percentage Change in High Density Lipoprotein (HDL)-Cholesterol
Percentage change in HDL-cholesterol (measured in 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.
Measured: Baseline (week 0), week 12
Percentage Change in Very Low Density Lipoprotein (VLDL)-Cholesterol
Percentage change in VLDL-cholesterol (measured in mmol/L) 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.
Measured: Baseline (week 0), week 12
Percentage Change in Triglycerides
Percentage change in triglycerides (measured in 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.
Measured: Baseline (week 0), week 12
Percentage Change in Total Apolipoprotein B (Apo B)
Percentage change in Apo B (measured in 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.
Measured: Baseline (week 0), week 12
Percentage Change in Total Apolipoprotein CIII (Apo CIII)
Percentage change in Apo CIII (measured in 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.
Measured: Baseline (week 0), week 12
Change in Total Lipoprotein(a) (Lp[a]): Ratio to Baseline
Change in total Lp(a) (measured in mg/dL) at week 12 is presented as ratio to baseline. 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.
Measured: Baseline (week 0), week 12
Number of Treatment-emergent Adverse Events (TEAEs)
An adverse events (AE) is any untoward medical occurrence in a clinical trial participant that is temporally associated with the use of an investigational medicinal product (IMP), whether or not considered related to the IMP. All presented AEs are TEAEs. TEAEs was the number of AEs recorded during 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.
Measured: From baseline (week 0) to 138 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2021
- Study start3 Aug 2021
- Primary completion26 Apr 2022
- Study completion20 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Atherosclerotic Cardiovascular DiseaseStudies of the same condition, open and under way.
- More trials run by Novo Nordisk A/SThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 267 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novo Nordisk A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Transparency (dept. 1452), Study director, Novo Nordisk A/S
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04992065
- Sponsor's protocol ID
- NN6435-4697
- Other IDs
- U1111-1252-3392, 2020-002630-32, 151409
- Status last verified
- Jun 2025
- First submitted
- 28 Jul 2021
- Last updated
- 8 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
Publications
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.
PubMed 38310920
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04992065
- Acronym / sponsor ID
- NN6435-4697
- Conditions
- Atherosclerotic Cardiovascular Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 267 participants (actual)
- Lead sponsor
- Novo Nordisk A/SIndustry (pharma, biotech, devices)
- Study start
- 3 Aug 2021 (actual)
- Primary completion
- 26 Apr 2022 (actual)
- Study completion
- 20 Jun 2022 (actual)
- First posted
- 5 Aug 2021 (actual)
- Results
- Posted 8 Jun 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Oral NNC0385-0434 15 mg once-daily (OD) | Experimental | Drug: NNC0385-0434 A 15 mg15 mg NNC0385-0434 co-formulated with 500 mg Salcaprozate sodium (SNAC) tablet once daily |
| Oral placebo (NNC0385-0434 15 mg) | Placebo comparator | Other: 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 | Experimental | Drug: NNC0385-0434 A 40 mg40 mg study drug co-formulated with 500 mg SNAC tablet once daily |
| Oral placebo (NNC0385-0434 40 mg) | Placebo comparator | Other: Placebo I A (for NNC0385-0434 A 40 mg)placebo administered as tablets (without SNAC) once daily |
| Oral NNC0385-0434 100 mg | Experimental | Drug: NNC0385-0434 A 100 mg100 mg NNC0385-0434 co-formulated with 500 mg SNAC tablet once daily (51 participants) |
| Oral placebo (NNC0385-0434 100 mg) | Placebo comparator | Other: Placebo II A (for NNC0385-0434 A 100 mg)placebo administered as tablets (without SNAC) once daily |
| Subcutaneous evolocumab 140 mg Q2W | Active comparator | Drug: 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 |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Males or females of non-childbearing potential.
- Established atherosclerotic cardiovascular disease (ASCVD) (criteria a) or ASCVD risk (criteria b):
- 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.
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NNC0385-0434 A 15 mg15 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). | Drug | Oral NNC0385-0434 15 mg once-daily (OD) |
| NNC0385-0434 A 40 mg40 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). | Drug | Oral NNC0385-0434 40 mg OD |
| 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 | Other | Oral placebo (NNC0385-0434 15 mg) |
| NNC0385-0434 A 100 mg100 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). | Drug | Oral NNC0385-0434 100 mg |
| 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 | Other | Oral placebo (NNC0385-0434 40 mg) |
| 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 | Other | Oral placebo (NNC0385-0434 100 mg) |
| 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 | Drug | Subcutaneous evolocumab 140 mg Q2W |
Primary outcome
Percentage Change in Low-density Lipoprotein (LDL)-Cholesterol
Time frame: Baseline (week 0), week 12
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.
8 secondary outcomes
Percentage Change in Total Cholesterol
Time frame: Baseline (week 0), week 12
Percentage Change in High Density Lipoprotein (HDL)-Cholesterol
Time frame: Baseline (week 0), week 12
Percentage Change in Very Low Density Lipoprotein (VLDL)-Cholesterol
Time frame: Baseline (week 0), week 12
Percentage Change in Triglycerides
Time frame: Baseline (week 0), week 12
Percentage Change in Total Apolipoprotein B (Apo B)
Time frame: Baseline (week 0), week 12
Percentage Change in Total Apolipoprotein CIII (Apo CIII)
Time frame: Baseline (week 0), week 12
Change in Total Lipoprotein(a) (Lp[a]): Ratio to Baseline
Time frame: Baseline (week 0), week 12
Number of Treatment-emergent Adverse Events (TEAEs)
Time frame: From baseline (week 0) to 138 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 38310920Koren 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.
- Individual participant dataSharing planned: Yes. According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Transparency (dept. 1452) study director
Novo Nordisk A/S
44 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NNC0385-0434 A 15 mg, NNC0385-0434 A 40 mg and NNC0385-0434 A 100 mg in people with Atherosclerotic Cardiovascular Disease, run by Novo Nordisk A/S at 44 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 44 sites in United States, Greece, Netherlands, Poland, Belgium and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage Change in Low-density Lipoprotein (LDL)-Cholesterol (time frame: Baseline (week 0), week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04992065, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2025.