Clinical Trials Register

Summary
EudraCT Number:	2019-003688-23
Sponsor's Protocol Code Number:	20180109
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-10-08
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2019-003688-23

A.3

Full title of the trial

A Double-blind, Randomized, Placebo-controlled Phase 2 Study to Evaluate Efficacy, Safety, and Tolerability of Olpasiran AMG 890 (a GalNAc-conjugated Small Interfering RNA [siRNA]) in Subjects with Elevated Lipoprotein(a)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Olpasiran trials of Cardiovascular Events And LipoproteiN(a) reduction – DOSE Finding Study

A.4.1

Sponsor's protocol code number

20180109

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Amgen Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Amgen Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Amgen Nederland
B.5.2	Functional name of contact point	Medical Information the Netherlands
B.5.3	Address:
B.5.3.1	Street Address	Minervum 7061
B.5.3.2	Town/ city	Breda
B.5.3.3	Post code	4800 DH
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31765732500
B.5.5	Fax number	+31765736838
B.5.6	E-mail	medinfo@amgen.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Olpasiran
D.3.2	Product code	AMG 890
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Olpasiran
D.3.9.3	Other descriptive name	AMG 890
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Olpasiran
D.3.2	Product code	AMG 890
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Olpasiran
D.3.9.3	Other descriptive name	AMG 890
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	75
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Olpasiran
D.3.2	Product code	AMG 890
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Olpasiran
D.3.9.3	Other descriptive name	AMG 890
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Cardiovascular Disease

E.1.1.1

Medical condition in easily understood language

Atherosclerosis

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10051614
E.1.2	Term	Arteriosclerotic cardiovascular disease
E.1.2	System Organ Class	100000004866

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of the trial is to evaluate the effect of Olpasiran administered subcutaneous (SC) every 12 weeks (Q12W) compared with placebo, on percent change from baseline in Lp(a) after 36 weeks of treatment

E.2.2

Secondary objectives of the trial

To evaluate the effect of Olpasiran administered SC Q12W compared with placebo, on percent change from baseline in:
- Lp(a) after 48 weeks of treatment
- Low-density lipoprotein cholesterol (LDL-C) after 36 and 48 weeks of treatment
- Apolipoprotein(B) (ApoB) after 36 and 48 weeks of treatment

To characterize the pharmacokinetic (PK) properties of Olpasiran

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subjects are eligible to be included in the study only if all of the following criteria apply:

101 Subject has provided informed consent prior to initiation of any study specific
activities/procedures.
102 Age 18 to 80 years
103 Fasting Lp(a) > 150 nmol/L during screening by central laboratory (approximately corresponds to
> 60 mg/dL: note that molarity determines eligibility)
104 Atherosclerotic cardiovascular disease based on 1 of the following:
• History of coronary revascularization with percutaneous coronary intervention (PCI) or coronary
artery bypass grafting (CABG)
• Diagnosis of coronary artery disease with or without prior myocardial infarction
• Diagnosis of atherosclerotic cerebrovascular disease
• Diagnosis of peripheral arterial disease
105 For subjects receiving lipid-altering therapy (not required to participate in this
study), lipid-altering therapy, including statin dose, must remain stable per local
guidelines for ≥ 4 weeks prior to and during screening

E.4

Principal exclusion criteria

Subjects are excluded from the study if any of the following criteria apply:

Disease Related
201 Severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) <
30 mL/min/1.73 m2 during screening
202 History or clinical evidence of active liver disease or hepatic dysfunction, defined as aspartate
aminotransferase (AST) or alanine aminotransferase (ALT) > 3 × upper limit of normal (ULN), or
total bilirubin (TBL) > 2 × ULN during screening
203 Inherited or other bleeding disorders
204 Recent major cardiovascular event (myocardial infarction, unstable angina, PCI, CABG, or stroke)
within 6 months prior to day 1
205 Planned cardiac surgery, PCI or carotid stenting, or planned major non-cardiac surgery during
the study period

Other Medical Conditions
206 Malignancy (except non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal
carcinoma in situ, or stage 1 prostate carcinoma) within the last 5 years prior to day 1
207 Moderate to severe heart failure (New York Heart Association (NYHA) Functional Classification
III or IV at day 1) or last known left ventricular ejection fraction < 30%
208 Uncontrolled cardiac arrhythmia defined as recurrent and highly symptomatic ventricular
tachycardia, atrial fibrillation with rapid ventricular response, or supraventricular tachycardia
that are not controlled by medications, in the past 3 months prior to day 1
209 Uncontrolled hypertension at day 1, defined as an average systolic blood pressure of ≥ 160
mmHg or an average diastolic blood pressure of ≥ 100 mmHg at rest
210 Fasting triglycerides ≥ 400 mg/dL (4.5 mmol/L) during screening
211 Type 1 diabetes or poorly controlled (HbA1c ≥ 8.5%) type 2 diabetes mellitus as determined by
central laboratory at screening
212 Known active infection or major hematologic, renal, metabolic, gastrointestinal or endocrine
dysfunction, or a chronic disease or infection (eg, HIV) that is not currently stable and appropriately managed in the judgment of the investigator at day 1

Prior/Concomitant Therapy
213 Previously received treatment with antisense oligonucleotides (ASO), siRNA therapies (eg,
inclisiran), or any experimental therapy targeting Lp(a)
215 Currently undergoing lipid apheresis or < 3 months since last apheresis treatment at day 1
216 Subject has taken a cholesterol ester transfer protein inhibitor (eg, anacetrapib, dalcetrapib,
evacetrapib) or lomitapide in the last 12 months prior to day 1
226 Currently receiving, or < 3 months at day 1 since receiving > 200 mg/day Niacin

Prior/Concurrent Clinical Study Experience
217 Currently receiving treatment in another investigational device or drug study, or less than 30
days since ending treatment on another investigational device or drug study(ies). Other
investigational procedures while participating in this study are excluded.
218 Use of any herbal medicines, vitamins or supplements known to affect lipid metabolism (eg, fish
oils > 4000 mg/day, red yeast rice extract), within 30 days prior to day 1

Other Exclusions
219 Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed
during treatment and for an additional 90 days after the last dose of investigation product.
220 Female subjects of childbearing potential unwilling to use a highly effective method of
contraception during treatment and for an additional 90 days after the last dose of
investigation product. Refer to Section 11.5 for additional contraceptive information.
221 Female subjects of childbearing potential with a positive serum pregnancy test assessed at
Screening or positive urine pregnancy test on day 1.
222 Subject has known sensitivity to any of the products to be administered during dosing.
223 Subject likely to not be available to complete all protocol-required study visits or procedures,
and/or to comply with all required study procedures (eg, Clinical Outcome Assessments) to the
best of the subject and investigator’s knowledge.
224 History or evidence of any other clinically significant disorder, condition or disease (with the
exception of those outlined above) that, in the opinion of the investigator or Amgen physician,
if consulted, would pose a risk to subject safety or interfere with the study evaluation,
procedures or completion.

E.5 End points

E.5.1

Primary end point(s)

Percent change in Lp(a) from baseline at week 36

E.5.1.1

Timepoint(s) of evaluation of this end point

36 Weeks

E.5.2

Secondary end point(s)

1. Percentage change from baseline in:
- Lp(a) at week 48
- LDL-C at week 36 and week 48
- ApoB at week 36 and week 48

2. PK parameters for olpasiran including, but not limited to, maximum observed concentration (Cmax),
and the area under the concentration time curve (AUC)

E.5.2.1

Timepoint(s) of evaluation of this end point

Lp(a) at week 48
LDL-C at week 36 and week 48
ApoB at week 36 and week 48

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Canada

Japan

United States

Denmark

Iceland

Netherlands

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LSLV

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

240

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2020-10-08.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

240

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-06-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-09-22

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-11-08

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