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

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04992065
• Collaborator: (none)
• Enrollment: 255
• Locations: 43
• Arms: 7
• Actual Duration (Months): 11.5
• Patients Per Site: 5.9
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Atherosclerotic Cardiovascular Disease	Drug: NNC0385-0434 A 15 mg; Drug: NNC0385-0434 A 40 mg; Other: Placebo I A (for NNC0385-0434 A 15 mg); Drug: NNC0385-0434 A 100 mg; Other: Placebo I A (for NNC0385-0434 A 40 mg); Other: Placebo II A (for NNC0385-0434 A 100 mg); Drug: Evolocumab 140 mg/mL, Repatha®	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 255 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Masking Description: 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.
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Aug 3, 2021
• Actual Primary Completion Date: Apr 26, 2022
• Actual Study Completion Date: Jul 20, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Oral NNC0385-0434 15 mg once-daily (OD) 15 mg NNC0385-0434 co-formulated with 500 mg Salcaprozate sodium (SNAC) tablet once daily	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).
Placebo Comparator: Oral placebo (NNC0385-0434 15 mg) 15 MG placebo administered as tablets (without SNAC) once daily	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
Experimental: Oral NNC0385-0434 40 mg OD 40 mg study drug co-formulated with 500 mg SNAC tablet once daily	Drug: 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).
Placebo Comparator: Oral placebo (NNC0385-0434 40 mg) placebo administered as tablets (without SNAC) once daily	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
Experimental: Oral NNC0385-0434 100 mg 100 mg NNC0385-0434 co-formulated with 500 mg SNAC tablet once daily (51 participants)	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).
Placebo Comparator: Oral placebo (NNC0385-0434 100 mg) placebo administered as tablets (without SNAC) once daily	Other: 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
Active Comparator: Subcutaneous evolocumab 140 mg Q2W 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®; 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

Outcome Measures

Primary Outcome Measures

1. Change in low-density lipoprotein (LDL)-cholesterol [From baseline (week 0) to visit 9 (week 12)]

   percent

Secondary Outcome Measures

1. Change in total cholesterol [From baseline (week 0) to visit 9 (week 12)]

   Percent

2. Change in high density lipoprotein (HDL)-cholesterol [From baseline (week 0) to visit 9 (week 12)]

   percent

3. Change in very low density lipoprotein (VLDL)-cholesterol [From baseline (week 0) to visit 9 (week 12)]

   Percent

4. Change in triglycerides [From baseline (week 0) to visit 9 (week 12)]

   percent

5. Change in total Apo B [From baseline (week 0) to visit 9 (week 12)]

   percent

6. Change in total Apo CIII [From baseline (week 0) to visit 9 (week 12)]

   precent

7. Change in total Lipoprotein(a) ( Lp(a)) [From baseline (week 0) to visit 9 (week 12)]

   Ratio

8. Treatment-emergent adverse events [From baseline (week 0) to visit 10 (19 weeks + 4 days)]

   Number of events

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Palm Springs	California	United States	92262
2	Novo Nordisk Investigational Site	Boca Raton	Florida	United States	33434
3	Novo Nordisk Investigational Site	Fort Lauderdale	Florida	United States	33312
4	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32216
5	Novo Nordisk Investigational Site	Arlington Heights	Illinois	United States	60005
6	Novo Nordisk Investigational Site	Hammond	Louisiana	United States	70403
7	Novo Nordisk Investigational Site	Slidell	Louisiana	United States	70458
8	Novo Nordisk Investigational Site	Omaha	Nebraska	United States	68105
9	Novo Nordisk Investigational Site	Omaha	Nebraska	United States	68198
10	Novo Nordisk Investigational Site	Albany	New York	United States	12203
11	Novo Nordisk Investigational Site	West Seneca	New York	United States	14224
12	Novo Nordisk Investigational Site	Dallas	Texas	United States	75208
13	Novo Nordisk Investigational Site	Houston	Texas	United States	77079
14	Novo Nordisk Investigational Site	Aalst		Belgium	9300
15	Novo Nordisk Investigational Site	Brugge		Belgium	8000
16	Novo Nordisk Investigational Site	Genk		Belgium	3600
17	Novo Nordisk Investigational Site	Haine-Saint-Paul		Belgium	7100
18	Novo Nordisk Investigational Site	Hasselt		Belgium	3500
19	Novo Nordisk Investigational Site	Frankfurt		Germany	60389
20	Novo Nordisk Investigational Site	Freiburg		Germany	79106
21	Novo Nordisk Investigational Site	München		Germany	80636
22	Novo Nordisk Investigational Site	Villingen-Schwenningen		Germany	78048
23	Novo Nordisk Investigational Site	Athens		Greece	GR-11528
24	Novo Nordisk Investigational Site	Athens		Greece	GR-14233
25	Novo Nordisk Investigational Site	Athens		Greece	GR-15123
26	Novo Nordisk Investigational Site	Chaidari, Athens		Greece	GR-12462
27	Novo Nordisk Investigational Site	Chios		Greece	GR82100
28	Novo Nordisk Investigational Site	Saitama-shi, Saitama		Japan	338-0837
29	Novo Nordisk Investigational Site	Sendai-shi, Miyagi		Japan	983-0039
30	Novo Nordisk Investigational Site	Soka-shi, Saitama		Japan	340-0034
31	Novo Nordisk Investigational Site	Tokyo		Japan	192-0918
32	Novo Nordisk Investigational Site	Den Bosch		Netherlands	5223GZ
33	Novo Nordisk Investigational Site	Deventer		Netherlands	7416 SE
34	Novo Nordisk Investigational Site	Groningen		Netherlands	9728 NT
35	Novo Nordisk Investigational Site	Haarlem		Netherlands	2035 RC
36	Novo Nordisk Investigational Site	Nijmegen		Netherlands	6532 SZ
37	Novo Nordisk Investigational Site	Sneek		Netherlands	8601 ZR
38	Novo Nordisk Investigational Site	Gdansk		Poland	80-952
39	Novo Nordisk Investigational Site	Lubin		Poland	59-301
40	Novo Nordisk Investigational Site	Swidnik		Poland	21-040
41	Novo Nordisk Investigational Site	Warszawa		Poland	02-097
42	Novo Nordisk Investigational Site	Warszawa		Poland	04-073
43	Novo Nordisk Investigational Site	Warszawa		Poland	04-628

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

• Study Director: Clinical Transparency (dept. 1452), Novo Nordisk A/S

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT04992065
• Other Study ID Numbers: NN6435-4697; U1111-1252-3392; 2020-002630-32; 151409
• First Posted: Aug 5, 2021
• Last Update Posted: Jul 20, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Cardiovascular Diseases; Atherosclerosis; Evolocumab

Study Results

No Results Posted as of Jul 20, 2022