Clinical Trials Register

Summary
EudraCT Number:	2020-002755-38
Sponsor's Protocol Code Number:	CKJX839C12302
National Competent Authority:	Slovenia - JAZMP
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-12-02
Trial 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

Slovenia - JAZMP

A.2

EudraCT number

2020-002755-38

A.3

Full title of the trial

Two part (double-blind) inclisiran versus placebo [Year 1] followed by open-label inclisiran [Year 2] randomized multicentre study to evaluate safety, tolerability, and efficacy of inclisiran in adolescents (12 to less than 18 years) with homozygous familial hypercholesterolemia and elevated LDL-cholesterol (ORION-13)

Dvodelna (dvojno slepo obdobje za primerjavo inklisirana in placeba [1. leto], ki mu sledi nemaskirano obdobje jemanja inklisirana [2. leto]) randomizirana multicentrična raziskava za vrednotenje varnosti, prenašanja in učinkovitosti inklisirana pri mladostnikih (starih od 12 do manj kot 18 let) s homozigotno družinsko hiperholesterolemijo in zvišanimi vrednostmi LDL-holesterola (ORION-13)

A.3.1

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

Study to evaluate efficacy and safety of inclisiran in adolescents with homozygous familial hypercholesterolemia

A.4.1

Sponsor's protocol code number

CKJX839C12302

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/322/2023

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 Services Inc. Podružnica v Sloveniji
B.5.2	Functional name of contact point	Medical Information Desk
B.5.3	Address:
B.5.3.1	Street Address	Verovškova 57
B.5.3.2	Town/ city	Ljubljana
B.5.3.3	Post code	SI-1000
B.5.3.4	Country	Slovenia
B.5.4	Telephone number	+38613 007550
B.5.5	Fax number	+38613007595
B.5.6	E-mail	medinfo.slo@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	Yes
D.2.1.1.1	Trade name	Leqvio 284 mg solution for injection in pre-filled syringe
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
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 sodium
D.3.2	Product code	KJX839
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
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.3.9.1	CAS number	1639324-62-1
D.3.9.2	Current sponsor code	KJX839
D.3.9.4	EV Substance Code	SUB182427
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.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 in pre-filled syringe
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

Homozygous Familial Hypercholesterolemia

E.1.1.1

Medical condition in easily understood language

Homozygous Familial Hypercholesterolemia

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10057080
E.1.2	Term	Homozygous familial hypercholesterolemia
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to demonstrate superiority of inclisiran compared to placebo in reducing LDL-C [percent change] at Day 330 (Year 1) in adolescents (aged 12 to <18 years) with HoFH and elevated LDL-C

E.2.2

Secondary objectives of the trial

Evaluate the effect of inclisiran compared to placebo on reducing LDL-C [time-adjusted percent change] over Year 1.
Evaluate the effect of inclisiran compared to placebo (for Year 1) and long-term (up to Day 720), on lowering LDL-C, other lipoprotein and lipid parameters, and PCSK9 over time.
Evaluate the safety and tolerability of inclisiran compared to placebo (for Year 1) and long-term (up to Day 720), in adolescents (aged 12 to <18 years) with HoFH.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Homozygous Familial Hypercholesterolemia (HoFH) diagnosed by genetic confirmation.
Fasting LDL-C >130 mg/dL (3.4 mmol/L) at screening.
On maximally tolerated dose of statin (investigator’s discretion) with or without other lipid-lowering therapy; stable for ≥ 30 days before screening.
Estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2 at screening.

E.4

Principal exclusion criteria

Documented evidence of a null (negative) mutation in both LDLR alleles.
Heterozygous familial hypercholesterolemia (HeFH).
Active liver disease.
Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome.
Major adverse cardiovascular events within 1 month prior to randomization.
Previous treatment with monoclonal antibodies directed towards PCSK9 (within 90 days of screening).
Treatment with mipomersen or lomitapide (within 5 months of screening).
Recent and/or planned use of other investigational medicinal products or devices.

E.5 End points

E.5.1

Primary end point(s)

Percentage (%) change in low-density lipoprotein cholesterol (LDL-C) from baseline to Day 330.

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline and Day 330

E.5.2

Secondary end point(s)

Time-adjusted percent change in LDL-C from baseline after Day 90 and up to Day 330.
Percent change and absolute change in LDL-C from baseline up to Day 720.
Percent change and absolute change in other lipoprotein and lipid parameters from baseline up to Day 720.
Percent change and absolute change in proprotein convertase subtilisin/kexin type 9 (PCSK9) from baseline up to Day 720.

E.5.2.1

Timepoint(s) of evaluation of this end point

Baseline, after Day 90 up to Day 330.
Baseline, up to Day 720.
Baseline, up to Day 720.
Baseline, up to Day 720.

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

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

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

Yes

E.8.4

The trial involves multiple sites in the 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

Switzerland

Canada

Lebanon

Serbia

South Africa

United States

Viet Nam

France

Germany

Greece

Italy

Netherlands

Slovenia

Türkiye

E.8.7

Trial has a data monitoring committee

Yes

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

Yes

F.1.1

Number of subjects for this age range:

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)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

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 2020-12-02.

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

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)

Post-trial access may be offered

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

2020-12-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-12-11

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2024-11-18

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