Clinical Trials Register

Summary
EudraCT Number:	2018-004253-24
Sponsor's Protocol Code Number:	CLNP023B12001B
National Competent Authority:	Greece - EOF
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-11-15
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

Greece - EOF

A.2

EudraCT number

2018-004253-24

A.3

Full title of the trial

An open-label, non-randomized extension study to evaluate the long-term
efficacy, safety and tolerability of iptacopan (LNP023) in C3
glomerulopathy or idiopathic immune-complex-membranoproliferative
glomerulonephritis

Μία ανοιχτή, μη τυχαιοποιημένη μελέτη επέκτασης για την αξιολόγηση της μακροχρόνιας αποτελεσματικότητας, ασφάλειας και ανεκτικότητας του iptacopan (LNP023) στην C3 σπειραματοπάθεια ή ιδιοπαθή μεμβρανοϋπερπλαστική σπειραματονεφρίτιδα με παρουσία ανοσοσυμπλεγμάτων

A.3.1

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

Long-term efficacy, safety and tolerability of LNP023 in C3G or IC-MPGN

A.4.1

Sponsor's protocol code number

CLNP023B12001B

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 (Hellas) S.A.C.I.
B.5.2	Functional name of contact point	Veronique Schaaf
B.5.3	Address:
B.5.3.1	Street Address	12th klm of National Road Athens-Lamia (No.1)
B.5.3.2	Town/ city	Metamorphosi, Athens
B.5.3.3	Post code	GR-144 51
B.5.3.4	Country	Greece
B.5.4	Telephone number	+30 210 289 7152
B.5.5	Fax number	+30 210 283 5053
B.5.6	E-mail	veronique.schaaf@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	Yes
D.2.5.1	Orphan drug designation number	EU/3/18/2104
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.3.8	INN - Proposed INN	Iptacopan
D.3.9.2	Current sponsor code	LNP023
D.3.9.3	Other descriptive name	Iptacopan hydrochloride
D.3.9.4	EV Substance Code	SUB216376
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	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	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	Yes
D.2.5.1	Orphan drug designation number	EU/3/18/2104
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.3.8	INN - Proposed INN	Iptacopan
D.3.9.2	Current sponsor code	LNP023
D.3.9.3	Other descriptive name	LNP023 HYDROCHLORIDE SALT
D.3.9.4	EV Substance Code	SUB193714
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	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

C3 Glomerulopathy or idiopathic immune-complex membranoproliferative glomerulonephritis

E.1.1.1

Medical condition in easily understood language

Kidney Disorder

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10077827
E.1.2	Term	C3 glomerulopathy
E.1.2	System Organ Class	10038359 - Renal and urinary disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	27.0
E.1.2	Level	PT
E.1.2	Classification code	10089346
E.1.2	Term	Immune-complex membranoproliferative glomerulonephritis
E.1.2	System Organ Class	10038359 - Renal and urinary 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

Participants enrolling from study CLNP023X2202
•Primary Efficacy Objective (Cohort A - native C3G): To assess the effect of iptacopan on a 3-component composite renal endpoint in C3G participants at the 9-month visit
•Primary efficacy objective (Cohort B - transplanted kidney with recurrent C3G): To assess the effect of iptacopan on C3 deposit score at the 6 to 9 month visit
•Primary Safety Objective: To evaluate the long-term safety and tolerability of iptacopan in participants with C3G

Participants enrolling from study CLNP023B12301 or CLNP023B12302
• Primary Objective: To evaluate the long-term safety and tolerability of
iptacopan in participants with C3G or IC-MPGN

E.2.2

Secondary objectives of the trial

Participants enrolling from study CLNP023X2202
•To characterize the effect of treatment with iptacopan on a 2-component composite renal endpoint at the 9-month visit
• To assess the long-term effect of iptacopan on renal function (eGFR and UPCR) in C3G participants at the 9-month visit
• To assess the effect of iptacopan on proteinuria in C3G participants at the 3-month visit
• To describe the status of C3G disease progression based on glomerular histopathology in a renal biopsy at 6-9 months
• To evaluate the long-term effect of iptacopan on C3 at the 9-month visit
• To evaluate the pharmacokinetics of iptacopan in participants with prolonged treatment

Participants enrolling from study CLNP023B12301 or CLNP023B12302
• To evaluate the long-term effect of iptacopan on proteinuria
• To evaluate the long-term effect of iptacopan on eGFR
• To evaluate the long-term effect of iptacopan on a 2-component composite renal endpoint

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Participants must have completed the treatment period of the
CLNP023X2202, CLNP023B12301 or CLNP023B12302 study on study
drug.

E.4

Principal exclusion criteria

•Severe concurrent co-morbidities, e.g., advanced cardiac disease (New York Heart Association (NYHA) class IV), severe pulmonary arterial hypertension (WHO class IV), or any illness or medical condition that in the opinion of the investigator and sponsor is likely to prevent the patient from safely tolerating iptacopan or complying with the requirements of the study.
• Participants with an active systemic bacterial, viral or fungal infection within 14 days prior to screening,
or
The presence of fever ≥ 38oC (100.4oF) within 7 days prior to screening.
• History of human immunodeficiency virus (HIV) or any other immunodeficiency disease.
• History or current diagnosis of ECG abnormalities indicating significant risk of safety for participants.

E.5 End points

E.5.1

Primary end point(s)

Participants from study CLNP023X2202
1) A participant meets the requirements of the composite renal endpoint if they satisfy the following criteria at the 9-month visit in CLNP023B12001B: (1) a stable or improved eGFR compared to the baseline visit in CLNP023X2202 (≤10% reduction in eGFR), and (2) either ≥50% reduction compared to the baseline visit in CLNP023X2202 or a reduction to <300 mg/g in UPCR and (3) either a ≥50% increase in C3 compared to baseline or an increase to ≥90 mg/dL (i.e., ≥ the lower limit of normal (LLN)). Initiation of treatment with eculizumab or any other complement pathway modifying agent automatically designates the participant as not meeting the endpoint.
2) Change from baseline in the C3 Deposit Score (based on immunofluorescence microscopy) compared to baseline in the CLNP023X2202 study.
3) Occurrence of clinically significant vital signs (msDBP, msSBP, heart rate), ECGs, and safety laboratory measurements, as well as adverse events (AEs), AEs of special interest, and study drug discontinuation due to an AE (or any safety issue).

Participants from study CLNP023B12301 or CLNP023B12302
4) Occurrence of clinically significant vital signs (msDBP, msSBP, heart rate), ECGs, and safety laboratory measurements, as well as adverse events (AEs), AEs of special interest, and study drug discontinuation due to an AE (or any safety issue).

E.5.1.1

Timepoint(s) of evaluation of this end point

1) 9-month visit
2) 6- to 9- month visit
3) 9-month visit, end of study
4) 9-month visit, end of study

E.5.2

Secondary end point(s)

Participants from study CLNP023X2202
1) A participant is defined as achieving the composite renal endpoint if they meet the following criteria at the 9-month visit in CLNP023B12001B: (1) a stable or improved eGFR compared to the baseline visit in CLNP023X2202 (≤10% reduction in eGFR), and (2) either ≥50% reduction compared to the baseline visit in CLNP023X2202 or a reduction to <300 mg/g in UPCR. Initiation of treatment with eculizumab or any other complement pathway modifying agent automatically designates the participant as a not meeting the composite renal endpoint.
2) Change from baseline in log-transformed urine protein/creatinine ratio (UPCR), change from baseline in log-transformed urine albumin/creatinine ratio (UACR), change from baseline in serum creatinine concentration and change from baseline in estimated glomerular filtration rate (eGFR) at the 9-month visit in CLNP023B12001B.
3) Change from baseline in log-transformed urine protein/creatinine ratio (UPCR) and change from baseline in log-transformed urine albumin/creatinine ratio (UACR), at the 3-month visit in CLNP023B12001B.
4) Disease activity and chronicity scores from a renal biopsy at 6 to 9 months from entry to the CLNP023B12001B study. Biopsies will be compared to those obtained in the CLNP023X2202 study (if available).
5) Log-transformed ratio to baseline in serum C3 at the 9-month visit in CLNP023B12001B.
6) A participant is defined as achieving the composite renal endpoint if they meet the following criteria at times >9 months in CLNP023B12001B: (1) a stable or improved eGFR compared to the baseline visit in CLNP023X2202 (≤10% reduction in eGFR), and (2) either ≥50% reduction compared to the baseline visit in CLNP023X2202 or a reduction to <300 mg/g in UPCR and (3) either a ≥50% increase in C3 compared to baseline or an increase to ≥90 mg/dL (i.e., LLN). Initiation of treatment with eculizumab or any other complement pathway modifying agent automatically designates the participant as a not meeting the composite renal endpoint.
7) Change from baseline in log-transformed UPCR, log-transformed UACR, serum creatinine concentration and estimated glomerular filtration rate (eGFR) at times >9 months in CLNP023B12001B. Change in eGFR slope.
8) Log-transformed ratio to baseline in serum C3 at times >9 months in CLNP023B12001B.
9) Determine plasma iptacopan concentration up to 12 months at trough

Participants from studies CLNP023B12301 or CLNP023B12302
10) Change from initiation of iptacopan treatment in the core study in log-transformed UPCR over time.
11) Change from initiation of iptacopan treatment in the core study in eGFR over time
12) A participant is defined as meeting the requirements of the composite renal endpoint if they satisfy the eGFR (a stable or improved eGFR, i.e., ≤15% reduction in eGFR compared to the initiation of iptacopan treatment in the core study) and UPCR (≥50% reduction in UPCR compared to the initiation of iptacopan treatment in the core study) criteria assessed at a visit. Initiation of any complement pathway modifying agent or initiation/intensification of corticosteroid or immunosuppressant therapy, or renal replacement therapy automatically designates the participant as not having met the endpoint. The rate will be evaluated over time.

E.5.2.1

Timepoint(s) of evaluation of this end point

1) 9-month visit
2) 9-month visit
3) 3-month visit
4) 6- to 9-month visit
5) 9 month visit
6) >9 months
7) >9 months
8) >9 months
9) up to 12 months
10) End of study visit
11) End of study visit
12) End of study visit
13) End of study visit
14) 9-month visit
15) 9-month visit

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

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability

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

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.8.2.4

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

Argentina

Switzerland

Brazil

Canada

China

India

Israel

Japan

United Kingdom

United States

Belgium

Czechia

France

Germany

Greece

Italy

Netherlands

Spain

Türkiye

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

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)

Yes

F.1.2.1

Number of subjects for this age range:

158

F.1.3

Elderly (>=65 years)

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

183

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)

Participants will switch to commercial drug as study will end when the drug is commercially available

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

2022-12-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-12-02

P. End of Trial
P.	End of Trial Status	Ongoing

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