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

Novo Nordisk

Status and phase: Completed; Phase 2

Conditions: Atherosclerotic Cardiovascular Disease

Treatments: Other: Placebo II A (for NNC0385-0434 A 100 mg); Drug: NNC0385-0434 A 40 mg; Drug: NNC0385-0434 A 15 mg; Other: Placebo I A (for NNC0385-0434 A 40 mg); Drug: NNC0385-0434 A 100 mg; Drug: Evolocumab 140 mg/mL, Repatha®; Other: Placebo I A (for NNC0385-0434 A 15 mg)

Study type: Interventional

Funder types: Industry

Identifiers

NCT04992065

151409 (Other Identifier)

NN6435-4697

2020-002630-32 (EudraCT Number)

U1111-1252-3392 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 267 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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267 participants in 7 patient groups, including a placebo group

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

Experimental group

Description:

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

Treatment:

Drug: NNC0385-0434 A 15 mg

Oral placebo (NNC0385-0434 15 mg)

Placebo Comparator group

Description:

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

Treatment:

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

Oral NNC0385-0434 40 mg OD

Experimental group

Description:

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

Treatment:

Drug: NNC0385-0434 A 40 mg

Oral placebo (NNC0385-0434 40 mg)

Placebo Comparator group

Description:

placebo administered as tablets (without SNAC) once daily

Treatment:

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

Oral NNC0385-0434 100 mg

Experimental group

Description:

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

Treatment:

Drug: NNC0385-0434 A 100 mg

Oral placebo (NNC0385-0434 100 mg)

Placebo Comparator group

Description:

placebo administered as tablets (without SNAC) once daily

Treatment:

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

Subcutaneous evolocumab 140 mg Q2W

Active Comparator group

Description:

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

Treatment:

Drug: Evolocumab 140 mg/mL, Repatha®