Download PDF

Clinical Trial Results:
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

Summary
EudraCT number	2020-002630-32
Trial protocol	DE GR NL BE PL
Global end of trial date	20 Jun 2022

Results information
Results version number	v1(current)
This version publication date	04 Jul 2023
First version publication date	04 Jul 2023
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

NN6435-4697

ISRCTN number

US NCT number

NCT04992065

WHO universal trial number (UTN)

U1111-1252-3392

Sponsor organisation name

Novo Nordisk A/S

Sponsor organisation address

Novo Allé, Bagsvaerd, Denmark, 2880

Public contact

Clinical Reporting Office (2834), Novo Nordisk A/S, clinicaltrials@novonordisk.com

Scientific contact

Clinical Reporting Office (2834), Novo Nordisk A/S, clinicaltrials@novonordisk.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

27 Jul 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

20 Jun 2022

Was the trial ended prematurely?

Main objective of the trial

To demonstrate superiority of three dose levels of oral NNC0385-0434 versus placebo on percent change in low-density lipoprotein cholesterol (LDL-C) from baseline to week 12 in subjects with established ASCVD or ASCVD risk on maximally tolerated statin dose and other lipid-lowering therapy requiring further LDL-C reduction.

Protection of trial subjects

The trial was conducted in accordance with the Declaration of Helsinki and International Council of Harmonisation (ICH) Good Clinical Practice, including archiving of essential documents and Food and Drug Administration (FDA) 21 Code of Federal Regulation (CFR) 312.120.

Background therapy

Subjects were to continue their background medication (maximally tolerated dose of statins and other lipid-lowering therapies [except proprotein convertase subtilisin/kexin type 9 inhibition {PCSK9i} therapy, PCSK9 small interfering ribonucleic acid {siRNA} therapy and oral semaglutide therapy]) throughout the entire trial.

Evidence for comparator

Not applicable.

Actual start date of recruitment

03 Aug 2021

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 21

Country: Number of subjects enrolled

Germany: 38

Country: Number of subjects enrolled

Greece: 31

Country: Number of subjects enrolled

Japan: 29

Country: Number of subjects enrolled

Netherlands: 47

Country: Number of subjects enrolled

Poland: 44

Country: Number of subjects enrolled

United States: 57

Worldwide total number of subjects

267

EEA total number of subjects

181

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

128

From 65 to 84 years

139

85 years and over

Subject disposition

Top of page

Recruitment details

The trial was conducted at 42 sites in 7 countries as follows (number of sites that screened subjects/ number of sites that randomised subjects): Belgium (5/ 5); Germany (4/ 4); Greece (6/ 6); Japan (4/ 4); Netherlands (6/ 6); Poland (5/ 5); United States (12/ 12).

Screening details

Subjects were randomized to receive either one of 3 dose levels of NNC0385-0434, placebo (matched to NNC0385-0434) or evolocumab for 12 weeks.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Investigator, Subject

Blinding implementation details

The trial was double-blinded within dose level of oral NNC0385-0434 and size matched placebo arm. The subcutaneous (s.c.) evolocumab arm was open label.

Are arms mutually exclusive

Yes

NNC0385-0434 15 mg

Arm description

Subjects received 15 milligrams (mg) NNC0385-0434 (co-formulated with 500 mg salcaprozate sodium [SNAC]) tablet orally once daily for 12 weeks.

Arm type

Experimental

Investigational medicinal product name

NNC0385-0434 A 15 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received 15 mg NNC0385-0434 once daily in the morning in a fasting state. Subjects were advised to take tablet at least 30 minutes (min) before the first food, beverage or other oral medications of the day with up to half a glass of water (approximately 120 milliliters [mL]/ 4 fluid ounces).

NNC0385-0434 40 mg

Arm description

Subjects received 40 mg NNC0385-0434 (co-formulated with 500 mg SNAC) tablet orally once daily for 12 weeks.

Arm type

Experimental

Investigational medicinal product name

NNC0385-0434 A 40 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received 40 mg NNC0385-0434 once daily in the morning in a fasting state. Subjects were advised to take tablet at least 30 min before the first food, beverage or other oral medications of the day with up to half a glass of water (approximately 120 mL/ 4 fluid ounces).

NNC0385-0434 100 mg

Arm description

Subjects received 100 mg NNC0385-0434 (co-formulated with 500 mg SNAC) tablet orally once daily for 12 weeks.

Arm type

Experimental

Investigational medicinal product name

NNC0385-0434 A 100 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received 100 mg NNC0385-0434 once daily in the morning in a fasting state. Subjects were advised to take tablet at least 30 min before the first food, beverage or other oral medications of the day with up to half a glass of water (approximately 120 mL/ 4 fluid ounces).

Placebo

Arm description

Subjects received placebo matched to NNC0385-0434 (without SNAC) tablet orally once daily for 12 weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo (matched to NNC0385-0434)

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received placebo matched to NNC0385-0434 once daily in the morning in a fasting state. Subjects were advised to take tablet at least 30 min before the first food, beverage or other oral medications of the day with up to half a glass of water (approximately 120 mL/ 4 fluid ounces).

Evolocumab 140 mg

Arm description

Subjects received 140 mg evolocumab injection s.c. once every weeks for 12 weeks.

Arm type

Active comparator

Investigational medicinal product name

Repatha®

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received 140 mg evolocumab injection once every 2 weeks into areas of the abdomen, thigh, or upper arm that are not tender, bruised, red, or indurated. The evolocumab was injected using a pre-filled SureClick® autoinjector (single-use).

Number of subjects in period 1	NNC0385-0434 15 mg	NNC0385-0434 40 mg	NNC0385-0434 100 mg	Placebo	Evolocumab 140 mg
Started	53	53	53	54	54
Completed	53	53	53	54	54

Baseline characteristics

Top of page

Reporting group title

NNC0385-0434 15 mg

Reporting group description

Subjects received 15 milligrams (mg) NNC0385-0434 (co-formulated with 500 mg salcaprozate sodium [SNAC]) tablet orally once daily for 12 weeks.

Reporting group title

NNC0385-0434 40 mg

Reporting group description

Subjects received 40 mg NNC0385-0434 (co-formulated with 500 mg SNAC) tablet orally once daily for 12 weeks.

Reporting group title

NNC0385-0434 100 mg

Reporting group description

Subjects received 100 mg NNC0385-0434 (co-formulated with 500 mg SNAC) tablet orally once daily for 12 weeks.

Reporting group title

Placebo

Reporting group description

Subjects received placebo matched to NNC0385-0434 (without SNAC) tablet orally once daily for 12 weeks.

Reporting group title

Evolocumab 140 mg

Reporting group description

Subjects received 140 mg evolocumab injection s.c. once every weeks for 12 weeks.

Reporting group values	NNC0385-0434 15 mg	NNC0385-0434 40 mg	NNC0385-0434 100 mg	Placebo	Evolocumab 140 mg	Total
Number of subjects	53	53	53	54	54	267
Age Categorical
Units: Subjects
Age Continuous
Units: years
arithmetic mean (standard deviation)	64.1 ( 9.3 )	64.6 ( 8.6 )	65.2 ( 9.2 )	63.1 ( 8.6 )	64.5 ( 9.6 )	-
Gender Categorical
Units: Subjects
Female	17	17	14	17	17	82
Male	36	36	39	37	37	185

End points

Top of page

Reporting group title

NNC0385-0434 15 mg

Reporting group description

Subjects received 15 milligrams (mg) NNC0385-0434 (co-formulated with 500 mg salcaprozate sodium [SNAC]) tablet orally once daily for 12 weeks.

Reporting group title

NNC0385-0434 40 mg

Reporting group description

Subjects received 40 mg NNC0385-0434 (co-formulated with 500 mg SNAC) tablet orally once daily for 12 weeks.

Reporting group title

NNC0385-0434 100 mg

Reporting group description

Subjects received 100 mg NNC0385-0434 (co-formulated with 500 mg SNAC) tablet orally once daily for 12 weeks.

Reporting group title

Placebo

Reporting group description

Subjects received placebo matched to NNC0385-0434 (without SNAC) tablet orally once daily for 12 weeks.

Reporting group title

Evolocumab 140 mg

Reporting group description

Subjects received 140 mg evolocumab injection s.c. once every weeks for 12 weeks.

Primary: Change in low-density lipoprotein (LDL)-cholesterol

Top of page

End point title

Change in low-density lipoprotein (LDL)-cholesterol

End point description

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 subjects 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. Full analysis set (FAS) included all randomized subjects. Number of subjects analyzed = subjects with available data for this endpoint.

End point type

Primary

End point timeframe

From baseline (week 0) to visit 9 (week 12)

End point values	NNC0385-0434 15 mg	NNC0385-0434 40 mg	NNC0385-0434 100 mg	Placebo	Evolocumab 140 mg
Number of subjects analysed	51	52	49	52	49
Units: Percentage change of LDL-cholesterol
arithmetic mean (standard deviation)	-27 ( 19 )	-41 ( 37 )	-55 ( 20 )	6 ( 41 )	-59 ( 22 )

NNC0385-0434 15 mg vs Placebo

Statistical analysis description

LDL-C percentage change at week 12 from baseline responses were analysed using an analysis of covariance model with randomised treatment and strata as factors and baseline LDL-C as covariate.

Comparison groups

NNC0385-0434 15 mg v Placebo

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Treatment Difference

Point estimate

-31.95

Confidence interval

level

95%

sides

2-sided

lower limit

-43.02

upper limit

-20.87

NNC0385-0434 40 mg vs Placebo

Statistical analysis description

LDL-C percentage change at week 12 from baseline responses were analysed using an analysis of covariance model with randomised treatment and strata as factors and baseline LDL-C as covariate.

Comparison groups

NNC0385-0434 40 mg v Placebo

Number of subjects included in analysis

104

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Treatment Difference

Point estimate

-44.91

Confidence interval

level

95%

sides

2-sided

lower limit

-56.04

upper limit

-33.79

NNC0385-0434 100 mg vs Evolocumab 140 mg

Statistical analysis description

LDL-C percentage change at week 12 from baseline responses were analysed using an analysis of covariance model with randomised treatment and strata as factors and baseline LDL-C as covariate.

Comparison groups

NNC0385-0434 100 mg v Evolocumab 140 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Treatment Difference

Point estimate

3.43

Confidence interval

level

95%

sides

2-sided

lower limit

-7.81

upper limit

14.68

NNC0385-0434 15 mg vs Evolocumab 140 mg

Statistical analysis description

LDL-C percentage change at week 12 from baseline responses were analysed using an analysis of covariance model with randomised treatment and strata as factors and baseline LDL-C as covariate.

Comparison groups

NNC0385-0434 15 mg v Evolocumab 140 mg

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Treatment Difference

Point estimate

33.32

Confidence interval

level

95%

sides

2-sided

lower limit

22.16

upper limit

44.47

NNC0385-0434 40 mg vs Evolocumab 140 mg

Statistical analysis description

LDL-C percentage change at week 12 from baseline responses were analysed using an analysis of covariance model with randomised treatment and strata as factors and baseline LDL-C as covariate.

Comparison groups

NNC0385-0434 40 mg v Evolocumab 140 mg

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Treatment Difference

Point estimate

20.35

Confidence interval

level

95%

sides

2-sided

lower limit

9.21

upper limit

31.48

NNC0385-0434 100 mg vs Placebo

Statistical analysis description

LDL-C percentage change at week 12 from baseline responses were analysed using an analysis of covariance model with randomised treatment and strata as factors and baseline LDL-C as covariate.

Comparison groups

NNC0385-0434 100 mg v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Tretment Difference

Point estimate

-61.83

Confidence interval

level

95%

sides

2-sided

lower limit

-72.94

upper limit

-50.72

Secondary: Change in total cholesterol

Top of page

End point title

Change in total cholesterol

End point description

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 subjects 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. FAS included all randomized subjects. Number of subjects analyzed = subjects with available data for this endpoint.

End point type

Secondary

End point timeframe

From baseline (week 0) to visit 9 (week 12)

End point values	NNC0385-0434 15 mg	NNC0385-0434 40 mg	NNC0385-0434 100 mg	Placebo	Evolocumab 140 mg
Number of subjects analysed	52	52	50	53	52
Units: Percentage change of total cholesterol
arithmetic mean (standard deviation)	-14 ( 13 )	-25 ( 27 )	-33 ( 11 )	4 ( 23 )	-38 ( 14 )

No statistical analyses for this end point

Secondary: Change in high-density lipoprotein (HDL)-cholesterol

Top of page

End point title

Change in high-density lipoprotein (HDL)-cholesterol

End point description

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 subjects 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. FAS included all randomized subjects. Number of subjects analyzed = subjects with available data for this endpoint.

End point type

Secondary

End point timeframe

From baseline (week 0) to visit 9 (week 12)

End point values	NNC0385-0434 15 mg	NNC0385-0434 40 mg	NNC0385-0434 100 mg	Placebo	Evolocumab 140 mg
Number of subjects analysed	52	52	47	53	51
Units: Percentage change of HDL-cholesterol
arithmetic mean (standard deviation)	4 ( 13 )	5 ( 16 )	7 ( 16 )	1 ( 14 )	5 ( 14 )

No statistical analyses for this end point

Secondary: Change in very low-density lipoprotein (VLDL)-cholesterol

Top of page

End point title

Change in very low-density lipoprotein (VLDL)-cholesterol

End point description

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 subjects 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. FAS included all randomized subjects. Overall number of subjects analyzed = subjects with available data for this endpoint.

End point type

Secondary

End point timeframe

From baseline (week 0) to visit 9 (week 12)

End point values	NNC0385-0434 15 mg	NNC0385-0434 40 mg	NNC0385-0434 100 mg	Placebo	Evolocumab 140 mg
Number of subjects analysed	52	52	50	53	52
Units: Percentage change of VLDL cholesterol
arithmetic mean (standard deviation)	5 ( 27 )	-7 ( 33 )	-15 ( 26 )	3 ( 41 )	-16 ( 24 )

No statistical analyses for this end point

Secondary: Change in triglycerides

Top of page

End point title

Change in triglycerides

End point description

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 subjects 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. FAS included all randomized subjects. Overall number of subjects analyzed = subjects with available data for this endpoint.

End point type

Secondary

End point timeframe

From baseline (week 0) to visit 9 (week 12)

End point values	NNC0385-0434 15 mg	NNC0385-0434 40 mg	NNC0385-0434 100 mg	Placebo	Evolocumab 140 mg
Number of subjects analysed	52	52	50	53	52
Units: Percentage change of triglycerides
arithmetic mean (standard deviation)	5 ( 27 )	-7 ( 31 )	-16 ( 27 )	2 ( 41 )	-16 ( 23 )

No statistical analyses for this end point

Secondary: Change in total Apolipoprotein B (Apo B)

Top of page

End point title

Change in total Apolipoprotein B (Apo B)

End point description

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 subjects 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. FAS included all randomized subjects. Overall number of subjects analyzed = subjects with available data for this endpoint.

End point type

Secondary

End point timeframe

From baseline (week 0) to visit 9 (week 12)

End point values	NNC0385-0434 15 mg	NNC0385-0434 40 mg	NNC0385-0434 100 mg	Placebo	Evolocumab 140 mg
Number of subjects analysed	51	52	49	53	53
Units: Percentage change of Apo B
arithmetic mean (standard deviation)	-20 ( 15 )	-34 ( 28 )	-48 ( 12 )	6 ( 31 )	-52 ( 17 )

No statistical analyses for this end point

Secondary: Change in total Apolipoprotein CIII (Apo CIII)

Top of page

End point title

Change in total Apolipoprotein CIII (Apo CIII)

End point description

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 subjects 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. FAS included all randomized subjects. Overall number of subjects analyzed = subjects with available data for this endpoint.

End point type

Secondary

End point timeframe

From baseline (week 0) to visit 9 (week 12)

End point values	NNC0385-0434 15 mg	NNC0385-0434 40 mg	NNC0385-0434 100 mg	Placebo	Evolocumab 140 mg
Number of subjects analysed	50	52	48	51	52
Units: Percentage change of Apo CIII
arithmetic mean (standard deviation)	-0 ( 20 )	-7 ( 24 )	-16 ( 15 )	2 ( 23 )	-15 ( 21 )

No statistical analyses for this end point

Secondary: Change in total lipoprotein(a) (Lp[a])

Top of page

End point title

Change in total lipoprotein(a) (Lp[a])

End point description

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 subjects 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. FAS included all randomized subjects. Overall number of subjects analyzed = subjects with available data for this endpoint.

End point type

Secondary

End point timeframe

From baseline (week 0) to visit 9 (week 12)

End point values	NNC0385-0434 15 mg	NNC0385-0434 40 mg	NNC0385-0434 100 mg	Placebo	Evolocumab 140 mg
Number of subjects analysed	52	52	50	53	53
Units: Ratio of Lipoprotein (a)
geometric mean (geometric coefficient of variation)	0.79 ( 34.2 )	0.70 ( 37.6 )	0.66 ( 40.0 )	0.99 ( 31.5 )	0.59 ( 43.4 )

No statistical analyses for this end point

Secondary: Treatment-emergent adverse events (TEAEs)

Top of page

End point title

Treatment-emergent adverse events (TEAEs)

End point description

An adverse events (AE) is any untoward medical occurrence in a clinical trial subject 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 subjects 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. Safety analysis set (SAS) included all subjects randomly assigned to trial treatment and who took at least 1 dose of trial product.

End point type

Secondary

End point timeframe

From baseline (week 0) to visit 10 (19 weeks + 4 days)

End point values	NNC0385-0434 15 mg	NNC0385-0434 40 mg	NNC0385-0434 100 mg	Placebo	Evolocumab 140 mg
Number of subjects analysed	53	53	53	54	54
Units: Events	82	60	65	56	81

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

From baseline (week 0) to visit 10 (19 weeks + 4 days)

Adverse event reporting additional description

All presented AEs are TEAEs. TEAEs are AEs recorded during the on-treatment period. SAS included all subjects randomly assigned to trial treatment and who took at least 1 dose of trial product.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

Reporting group title

NNC0385-0434 15 mg

Reporting group description

Subjects received 15 milligrams (mg) NNC0385-0434 (co-formulated with 500 mg salcaprozate sodium [SNAC]) tablet orally once daily for 12 weeks.

Reporting group title

NNC0385-0434 40 mg

Reporting group description

Subjects received 40 mg NNC0385-0434 (co-formulated with 500 mg SNAC) tablet orally once daily for 12 weeks.

Reporting group title

Evolocumab 140 mg

Reporting group description

Subjects received 140 mg evolocumab injection s.c. once every weeks for 12 weeks.

Reporting group title

Placebo

Reporting group description

Subjects received placebo matched to NNC0385-0434 (without SNAC) tablet orally once daily for 12 weeks.

Reporting group title

NNC0385-0434 100 mg

Reporting group description

Subjects received 100 mg NNC0385-0434 (co-formulated with 500 mg SNAC) tablet orally once daily for 12 weeks.

Serious adverse events	NNC0385-0434 15 mg	NNC0385-0434 40 mg	Evolocumab 140 mg	Placebo	NNC0385-0434 100 mg
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 53 (1.89%)	3 / 53 (5.66%)	3 / 54 (5.56%)	5 / 54 (9.26%)	1 / 53 (1.89%)
number of deaths (all causes)	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal adenocarcinoma
subjects affected / exposed	1 / 53 (1.89%)	0 / 53 (0.00%)	0 / 54 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Peripheral artery aneurysm
subjects affected / exposed	0 / 53 (0.00%)	1 / 53 (1.89%)	0 / 54 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Diastolic dysfunction
subjects affected / exposed	0 / 53 (0.00%)	0 / 53 (0.00%)	0 / 54 (0.00%)	1 / 54 (1.85%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Coronary artery stenosis
subjects affected / exposed	0 / 53 (0.00%)	0 / 53 (0.00%)	1 / 54 (1.85%)	0 / 54 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ventricular tachycardia
subjects affected / exposed	0 / 53 (0.00%)	0 / 53 (0.00%)	1 / 54 (1.85%)	0 / 54 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Loss of consciousness
subjects affected / exposed	0 / 53 (0.00%)	0 / 53 (0.00%)	1 / 54 (1.85%)	0 / 54 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myelopathy
subjects affected / exposed	0 / 53 (0.00%)	0 / 53 (0.00%)	0 / 54 (0.00%)	0 / 54 (0.00%)	1 / 53 (1.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chest discomfort
subjects affected / exposed	0 / 53 (0.00%)	1 / 53 (1.89%)	0 / 54 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Non-cardiac chest pain
subjects affected / exposed	0 / 53 (0.00%)	1 / 53 (1.89%)	0 / 54 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Dysphagia
subjects affected / exposed	1 / 53 (1.89%)	0 / 53 (0.00%)	0 / 54 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Biliary colic
subjects affected / exposed	0 / 53 (0.00%)	0 / 53 (0.00%)	1 / 54 (1.85%)	0 / 54 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Urticaria
subjects affected / exposed	0 / 53 (0.00%)	0 / 53 (0.00%)	0 / 54 (0.00%)	1 / 54 (1.85%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
subjects affected / exposed	0 / 53 (0.00%)	0 / 53 (0.00%)	0 / 54 (0.00%)	1 / 54 (1.85%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pain in extremity
subjects affected / exposed	0 / 53 (0.00%)	0 / 53 (0.00%)	0 / 54 (0.00%)	1 / 54 (1.85%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Herpes zoster
subjects affected / exposed	0 / 53 (0.00%)	0 / 53 (0.00%)	0 / 54 (0.00%)	1 / 54 (1.85%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	NNC0385-0434 15 mg	NNC0385-0434 40 mg	Evolocumab 140 mg	Placebo	NNC0385-0434 100 mg
Total subjects affected by non serious adverse events
subjects affected / exposed	16 / 53 (30.19%)	14 / 53 (26.42%)	17 / 54 (31.48%)	14 / 54 (25.93%)	19 / 53 (35.85%)
Investigations
Blood creatine phosphokinase increased
subjects affected / exposed	1 / 53 (1.89%)	0 / 53 (0.00%)	1 / 54 (1.85%)	4 / 54 (7.41%)	3 / 53 (5.66%)
occurrences all number	1	0	1	4	3
Vascular disorders
Hypertension
subjects affected / exposed	0 / 53 (0.00%)	1 / 53 (1.89%)	5 / 54 (9.26%)	0 / 54 (0.00%)	1 / 53 (1.89%)
occurrences all number	0	1	5	0	1
Nervous system disorders
Headache
subjects affected / exposed	4 / 53 (7.55%)	0 / 53 (0.00%)	3 / 54 (5.56%)	2 / 54 (3.70%)	0 / 53 (0.00%)
occurrences all number	4	0	3	2	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	4 / 53 (7.55%)	4 / 53 (7.55%)	1 / 54 (1.85%)	0 / 54 (0.00%)	2 / 53 (3.77%)
occurrences all number	4	4	1	0	5
Constipation
subjects affected / exposed	3 / 53 (5.66%)	0 / 53 (0.00%)	0 / 54 (0.00%)	1 / 54 (1.85%)	0 / 53 (0.00%)
occurrences all number	3	0	0	1	0
Nausea
subjects affected / exposed	1 / 53 (1.89%)	3 / 53 (5.66%)	0 / 54 (0.00%)	0 / 54 (0.00%)	3 / 53 (5.66%)
occurrences all number	1	4	0	0	3
Dyspepsia
subjects affected / exposed	1 / 53 (1.89%)	0 / 53 (0.00%)	1 / 54 (1.85%)	0 / 54 (0.00%)	3 / 53 (5.66%)
occurrences all number	2	0	1	0	4
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
subjects affected / exposed	0 / 53 (0.00%)	0 / 53 (0.00%)	3 / 54 (5.56%)	0 / 54 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	3	0	0
Musculoskeletal and connective tissue disorders
Myalgia
subjects affected / exposed	3 / 53 (5.66%)	0 / 53 (0.00%)	2 / 54 (3.70%)	2 / 54 (3.70%)	0 / 53 (0.00%)
occurrences all number	4	0	2	2	0
Infections and infestations
COVID-19
subjects affected / exposed	3 / 53 (5.66%)	8 / 53 (15.09%)	6 / 54 (11.11%)	6 / 54 (11.11%)	8 / 53 (15.09%)
occurrences all number	3	8	6	6	8
Nasopharyngitis
subjects affected / exposed	1 / 53 (1.89%)	3 / 53 (5.66%)	0 / 54 (0.00%)	3 / 54 (5.56%)	2 / 53 (3.77%)
occurrences all number	1	4	0	3	2

More information

Top of page

Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Clinical trials

Clinical Trial Results:
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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change in low-density lipoprotein (LDL)-cholesterol

Primary: Change in low-density lipoprotein (LDL)-cholesterol

Secondary: Change in total cholesterol

Secondary: Change in total cholesterol

Secondary: Change in high-density lipoprotein (HDL)-cholesterol

Secondary: Change in high-density lipoprotein (HDL)-cholesterol

Secondary: Change in very low-density lipoprotein (VLDL)-cholesterol

Secondary: Change in very low-density lipoprotein (VLDL)-cholesterol

Secondary: Change in triglycerides

Secondary: Change in triglycerides

Secondary: Change in total Apolipoprotein B (Apo B)

Secondary: Change in total Apolipoprotein B (Apo B)

Secondary: Change in total Apolipoprotein CIII (Apo CIII)

Secondary: Change in total Apolipoprotein CIII (Apo CIII)

Secondary: Change in total lipoprotein(a) (Lp[a])

Secondary: Change in total lipoprotein(a) (Lp[a])

Secondary: Treatment-emergent adverse events (TEAEs)

Secondary: Treatment-emergent adverse events (TEAEs)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: 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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change in low-density lipoprotein (LDL)-cholesterol

Primary: Change in low-density lipoprotein (LDL)-cholesterol

Secondary: Change in total cholesterol

Secondary: Change in total cholesterol

Secondary: Change in high-density lipoprotein (HDL)-cholesterol

Secondary: Change in high-density lipoprotein (HDL)-cholesterol

Secondary: Change in very low-density lipoprotein (VLDL)-cholesterol

Secondary: Change in very low-density lipoprotein (VLDL)-cholesterol

Secondary: Change in triglycerides

Secondary: Change in triglycerides

Secondary: Change in total Apolipoprotein B (Apo B)

Secondary: Change in total Apolipoprotein B (Apo B)

Secondary: Change in total Apolipoprotein CIII (Apo CIII)

Secondary: Change in total Apolipoprotein CIII (Apo CIII)

Secondary: Change in total lipoprotein(a) (Lp[a])

Secondary: Change in total lipoprotein(a) (Lp[a])

Secondary: Treatment-emergent adverse events (TEAEs)

Secondary: Treatment-emergent adverse events (TEAEs)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
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