Clinical Trials Register

Summary
EudraCT Number:	2016-003815-37
Sponsor's Protocol Code Number:	MDCO-PCS-16-01
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-01-26
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2016-003815-37

A.3

Full title of the trial

An open label, active comparator extension trial to assess the effect of long term dosing of inclisiran and evolocumab given as subcutaneous injections in subjects with high cardiovascular risk and elevated LDL-C (ORION-3)

A.3.1

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

Long term treatment with inclisiran and a comparison to evolocumab

A.3.2

Name or abbreviated title of the trial where available

ORION-3

A.4.1

Sponsor's protocol code number

MDCO-PCS-16-01

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03060577

A.5.4

Other Identifiers

Name:

Novartis protocol code

Number:

CKJX839A12201E1

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	Novartis Pharma AG
B.1.3.4	Country	Switzerland
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	Novartis Pharma AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Pharma AG
B.5.2	Functional name of contact point	Clinical Trial Information Desk
B.5.3	Address:
B.5.3.1	Street Address	Forum 1, Novartis Campus
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4056
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+41 61 324 1111
B.5.5	Fax number	+41 61 324 8001
B.5.6	E-mail	clinicaltrial.enquiries@novartis.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	Inclisiran for Injection
D.3.2	Product code	Inclisiran for Injection
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	Inclisiran
D.3.9.2	Current sponsor code	Inclisiran sodium
D.3.9.3	Other descriptive name	ALN-60212
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	200
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	Comparator
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	Yes
D.2.1.1.1	Trade name	Repatha (evolocumab) 140 mg (pre-filled pen)
D.2.1.1.2	Name of the Marketing Authorisation holder	Amgen Europe B.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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.3.4	Pharmaceutical form	Solution for injection in pre-filled pen
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	EVOLOCUMAB
D.3.9.2	Current sponsor code	evolocumab
D.3.9.3	Other descriptive name	evolocumab
D.3.9.4	EV Substance Code	SUB128552
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	140
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Hypercholesterolemia

E.1.1.1

Medical condition in easily understood language

Hypercholesterolemia, specifically, elevated low density lipoprotein cholesterol (LDL-C), is one of the major risk factors for the development of coronary heart disease (CHD)

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	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10020604
E.1.2	Term	Hypercholesterolemia
E.1.2	System Organ Class	100000004861

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the effect of inclisiran treatment on low density lipoprotein cholesterol (LDL-C) levels at Day 210 compared to Baseline of ORION-1 in Group 1 (inclisiran only arm).

E.2.2

Secondary objectives of the trial

• To evaluate the effects of inclisiran on the following (Group 1; inclisiran only arm):
- LDL-C levels over time
- PCSK9 levels over time
- Other lipids, lipoproteins, and apolipoproteins over time
- Proportion of subjects achieving target levels prespecified in global lipid guidelines
- Proportion of subjects at least 50% LDL-C reduction from Baseline of ORION-1 over time
- Individual responsiveness to inclisiran
- To evaluate the long term safety and tolerability of inclisiran (Group 1; inclisiran only arm)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Completion of study MDCO-PCS-15-01 and no contraindications to receiving inclisiran or evolocumab.
2. Willing and able to give informed consent before initiation of any study-related procedures and willing to comply with all required study procedures.
3. Willing to self-inject.

E.4

Principal exclusion criteria

1. Any uncontrolled or serious disease, or any medical or surgical condition, that may either interfere with participation in the clinical study, and/or put the subject at significant risk (according to investigator’s [or delegate’s] judgment) if he/she participates in the clinical study.
2. An underlying known disease, or surgical, physical, or medical condition that, in the opinion of the investigator (or delegate) might interfere with interpretation of the clinical study results.
3. Serious comorbid disease in which the life expectancy of the subject is shorter than the duration of the trial (eg, acute systemic infection, cancer, or other serious illnesses).
4. Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or unexplained alanine aminotransferase (ALT), aspartate aminotransferase (AST), elevation >2x the upper limit of normal (ULN), or total bilirubin elevation >1.5x ULN at study Entry Visit, confirmed by a repeat abnormal measurement at least 1 week apart.
5. Females who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least two methods of contraception (eg, oral contraceptives, barrier methods, approved contraceptive implant, long- term injectable contraception, intrauterine device or tubal ligation) for the entire duration of the trial. Women who are >2 years postmenopausal defined as ≥1 year since last menstrual period AND if less than 55 years old with a negative pregnancy test within 24 hours of entry into the study or surgically sterile are exempt. Exemptions from this exclusion.criterion:
a. Women >2 years postmenopausal (defined as 1 year or longer since their last menstrual period) AND more than 55 years of age
b. Postmenopausal women (as defined above) and less than 55 years old with a negative pregnancy test within 24 hours of enrollment
c. Women who are surgically sterilized at least 3 months prior to enrollment
6. Males who are unwilling to use an acceptable method of birth control during the entire study period (ie, condom with spermicide).
7. Treatment with investigational medicinal products other than
inclisiran or devices within 30 days or five half/lives, whichever is
longer.
8. Planned use of other investigational medicinal products other than inclisiran or devices during the course of the study.
9.Subjects with a history of a serious hypersensitivity reaction to evolocumab or any of the excipients.
10. Previous or current treatment (within 90 days of study entry) with monoclonal antibodies directed towards PCSK9.
11. Any condition that according to the investigator could interfere with the conduct of the study, such as but not limited to:
a. Inappropriate for this study, including subjects who are unable to communicate or to cooperate with the investigator.
b. Unable to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study (including subjects whose cooperation is doubtful due to drug abuse or alcohol dependency).
c. Unlikely to comply with the protocol requirements, instructions, and study-related restrictions (eg, uncooperative attitude, inability to return for follow-up visits, and improbability of completing the study).
d. Involved with, or a relative of, someone directly involved in the conduct of the study.
e. Any known cognitive impairment (eg, Alzheimer’s disease).

E.5 End points

E.5.1

Primary end point(s)

Primary Endpoint (Group 1; inclisiran only arm):
• Percentage change from Baseline of ORION-1 in LDL-C at Day 210 in this study (Group 1; inclisiran only arm)

E.5.1.1

Timepoint(s) of evaluation of this end point

Included in previous section.

E.5.2

Secondary end point(s)

Secondary Endpoints (Group 1; Inclisiran Only Arm):
• Change and percentage change from Baseline of ORION-1 in LDL-C over time in this study
• Change and percentage change from Baseline of ORION-1 in PCSK9 levels over time in this study
• Change and percentage change from Baseline of ORION-1 in other lipids, lipoproteins, and apolipoproteins over time in this study
• Proportion of subjects with ≥50% LDL-C reduction from Baseline of ORION-1 at each time point
• Individual responsiveness to inclisiran defined as the number of subjects reaching on treatment LDL-C levels of <25 mg/dL, <50 mg/dL, <70 mg/dL, and <100 mg/dL at any time point
• Change and percentage change in LDL-C at Day 210 compared to Day 870 of ORION-3
• Long term safety and tolerability of inclisiran treatment

E.5.2.1

Timepoint(s) of evaluation of this end point

Included in previous section

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

E.6.7

Pharmacodynamic

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

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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)

Yes

E.8.2.2

Placebo

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

Canada

Germany

Netherlands

United Kingdom

United States

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

LVLS

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:

198

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

184

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

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

254

F.4.2.2

In the whole clinical trial

382

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)

Subjects enrolled into this extension study will receive study drug for 4 years (or until the investigator’s recommendation of discontinuation, sponsor’s recommendation of discontinuation, the subject’s decision to discontinue for any reason, or until an administrative decision is made to end the study). At this time EOS evaluations will be conducted at the EOS visit.

Opportunity will be provided to enroll into ORION-8.

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

2017-04-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-03-14

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-12-17

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

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