Clinical Trials Register

Summary
EudraCT Number:	2014-005338-74
Sponsor's Protocol Code Number:	CLFG316X2201
National Competent Authority:	Lithuania - SMCA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-06-09
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

Lithuania - SMCA

A.2

EudraCT number

2014-005338-74

A.3

Full title of the trial

An open-label proof of concept study to assess the efficacy, safety and pharmacokinetics of LFG316, an anti-C5 monoclonal antibody in patients with paroxysmal nocturnal hemoglobinuria (PNH)

Atviras koncepcijos patvirtinimo tyrimas prieš C5 veikiančio monokloninio antikūno LFG316 veiksmingumui, saugumui ir farmakokinetikai įvertinti, skiriant pacientams, kuriems yra paroksizminė naktinė hemoglobinurija (PNH)

A.3.1

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

To find out whether LFG316 is able to reduce the destruction of red blood cells in patients with PNH

A.3.2

Name or abbreviated title of the trial where available

CLFG316X2201

A.4.1

Sponsor's protocol code number

CLFG316X2201

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 Services 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 Services 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	SIA Novartis Baltics Lithuanian Branch
B.5.2	Functional name of contact point	Clinical Trial Information Desk
B.5.3	Address:
B.5.3.1	Street Address	Upės str. 19
B.5.3.2	Town/ city	Vilnius
B.5.3.3	Post code	LT-08128
B.5.3.4	Country	Lithuania
B.5.4	Telephone number	+370 5 269 1650
B.5.5	Fax number	-
B.5.6	E-mail	DRA.Lithuania@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.3.2	Product code	LFG316
D.3.4	Pharmaceutical form	Lyophilisate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	No
D.3.9.2	Current sponsor code	LFG316
D.3.9.3	Other descriptive name	human monoclonal antibody directed against complement 5 protein
D.3.9.4	EV Substance Code	SUB32390
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	100
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.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.3.2	Product code	LFG316
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	No
D.3.9.2	Current sponsor code	LFG316
D.3.9.3	Other descriptive name	human monoclonal antibody directed against complement 5 protein
D.3.9.4	EV Substance Code	SUB32390
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	50
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.IMP: 3
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	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/20/2281
D.3 Description of the IMP
D.3.1	Product name	iptacopan
D.3.2	Product code	LNP023
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	LNP023 HYDROCHLORIDE SALT
D.3.9.4	EV Substance Code	SUB180361
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	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: 4
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	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/20/2281
D.3 Description of the IMP
D.3.1	Product name	iptacopan
D.3.2	Product code	LNP023
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	LNP023 HYDROCHLORIDE SALT
D.3.9.4	EV Substance Code	SUB180361
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	50
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Paroxysmal nocturnal hemoglobinuria

E.1.1.1

Medical condition in easily understood language

Rare and serious blood disease that causes the destruction of red blood cells

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

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	10055629
E.1.2	Term	Paroxysmal nocturnal hemoglobinuria
E.1.2	System Organ Class	100000004857

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

•To assess the effect of LFG316 on the reduction of intravascular hemolysis in PNH patients

E.2.2

Secondary objectives of the trial

•To assess the tolerability and pharmacokinetics of LFG316 in patients with PNH

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Male and female patients >= 18 years old with a diagnosis of PNH prior to screening. Based on local requirements (applicable in Czech Republic) only patients between the age of 18-65
(inclusive) with a diagnosis of PNH prior to screening may be eligible for inclusion in this study.
•A documented PNH clone size of ≥10% by RBCs and/or granulocytes, measured by GPI-deficiency on flow cytometry.
•Serum LDH levels at least 1.5-fold above the upper limit of normal (ULN) at screening.
•Negative pregnancy test for women of child bearing potential at screening.
•Previous vaccination against Neisseria meningitidis types A, C, Y and W-135 is required at least 2 weeks prior to first dosing. Vaccination against meningitidis type B should be conducted if available and acceptable by local regulations, at least 2 weeks prior to first dosing.
•Subjects to be included in this study after protocol amendment 6 also have to fulfill criterion: PNH patients that are carriers of the C5 gene minor variants as defined by nucleic acid changes that lead to amino acid
exchanges in position p.Arg885.
•Additional inclusion criteria for period 4
- Patients participating in period 3 of the current study who are willing to join long term extension study with LNP023 (CLNP023C12001B)
- Previous vaccination for the prevention of S. pneumoniae and H. influenzae at least 2 weeks prior to first dosing with LNP023 if locally available. If LNP023 treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment must be initiated.

E.4

Principal exclusion criteria

•Known or suspected hereditary complement deficiency.
•History of recurrent meningitis, history of meningococcal meningitis despite vaccination
•Presence or suspicion (based on judgment of the investigator) of severe active bacterial infection within 2 weeks prior to first dose of LFG316, or severe recurrent bacterial infections .
•Under active therapy with other agents interfering with the complement system
•Co-morbidities that are a likely caused by underlying autoimmune diseases other than PNH
•Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 50 days after the last dose of LFG316.
•Severe concurrent co-morbidites,eg: patients with severe kidney disease (dialysis),advanced cardiac disease (NYHA class IV) severe pulmonary artierial hypertension (WHO classIV), unstable thrombotic event not amenable to active treatment as judged by the investigator.
•Either on of the following laboratory abnormalities at screening:
a. Neutrophils <0.5 x 1000000000/L
b.Platelets<30x1000000000/L
•Prohibited medication : targeting complement pathway. For period 4 only :co-medications that inhibit multiple disposition mechanisms of LNP023, Strong CYP2C8 inhibitors such as Clopidogrel, Compounds that have a narrow therapeutic index and are substrates for Pglycoproteins

E.5 End points

E.5.1

Primary end point(s)

•Reduction in serum LDH levels within the first 4 weeks of treatment
•Reduction in serum LDH levels over the entire treatment period.

E.5.1.1

Timepoint(s) of evaluation of this end point

Weekly in Period 1 and every 14 days in Period 2.
Patients participating in extension Period 3 will roll over from the last dosing visit of period 2 to the first visit (which includes drug administration) of period 3. The same assessment schedule applied in Period 1 and 2 will be applied between the last dosing visit of Period 2 and the first visit of Period 3.
Patients participating in period 3 will have the option to complete the period 3 Follow up and Study Completion evaluation or to continue with study period 4 which is a pre-requisite for their eligibility to join the long-term extension study CLNP023C12001B.
Patients participating in period 4, will complete their Study Completion evaluation approximately one week after last LNP023 treatment administered as a part of this study.

E.5.2

Secondary end point(s)

•Standard safety monitoring with increased vigilance for infections
•Measurement of serum concentrations of LFG316

E.5.2.1

Timepoint(s) of evaluation of this end point

Safety
Weekly in Period 1 and every 2 weeks in Period 2
Serum concentration
Weekly in Period 1
Every 4 weeks in Period 2
Patients participating in extension Period 3 will roll over from the last dosing visit of period 2 to the first visit (which includes drug administration) of period 3. The same assessment schedule applied in Period 1 and 2 will be applied between the last dosing visit of Period 2 and the first visit of Period 3.
Patients participating in period 3 will have the option to complete the period 3 Follow up and Study Completion evaluation or to continue with study period 4.
Patients participating in period 4, will complete their Study Completion evaluation approximately one week after last LNP023 treatment administered as a part of this study.

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

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

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

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)

E.8.2.2

Placebo

E.8.2.3

Other

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

Japan

Lithuania

Czechia

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:

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

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)

The investigator must provide follow-up medical care for all subjects who are prematurely withdrawn from the study, or must refer them for appropriate ongoing care.This care may include enrollment in an extension study.
Each subject will be asked to complete this study in its entirety (period 1 and period 2) and they may be offered to enter an additional extension trial, provided LFG316 shows benefit as defined by the response criteria.

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

2015-07-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-06-25

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-05-24

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