Clinical Trials Register

Summary
EudraCT Number:	2018-000031-28
Sponsor's Protocol Code Number:	CLKA651X2202
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-10-01
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 - PEI

A.2

EudraCT number

2018-000031-28

A.3

Full title of the trial

A randomized, active-controlled, patient and investigator-masked, multiple dose proof-of-concept study of intravitreal LKA651 in patients with diabetic macular edema

A.3.1

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

A Proof of concept study of intravitreal LKA651 in patients with macular edema

A.4.1

Sponsor's protocol code number

CLKA651X2202

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 GmbH
B.5.2	Functional name of contact point	Medizinischer Infoservice (MCC)
B.5.3	Address:
B.5.3.1	Street Address	Roonstrasse 25
B.5.3.2	Town/ city	Nürnberg
B.5.3.3	Post code	90429
B.5.3.4	Country	Germany
B.5.4	Telephone number	+49 911 273-12100
B.5.5	Fax number	+49 911 27312160
B.5.6	E-mail	infoservice.novartis@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	LKA651
D.3.2	Product code	LKA651
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	Intravitreal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LKA651
D.3.9.2	Current sponsor code	LKA651
D.3.9.3	Other descriptive name	LKA651
D.3.9.4	EV Substance Code	SUB177591
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	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	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	Lucentis
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
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.3.1	Product name	Lucentis
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	Intravitreal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	RANIBIZUMAB
D.3.9.1	CAS number	347396-82-1
D.3.9.2	Current sponsor code	RFB002
D.3.9.4	EV Substance Code	SUB22314
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	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	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	Lucentis
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
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.3.1	Product name	Lucentis
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	Intravitreal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	RANIBIZUMAB
D.3.9.1	CAS number	347396-82-1
D.3.9.2	Current sponsor code	RBF002
D.3.9.4	EV Substance Code	SUB22314
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	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

diabetic macular edema

E.1.1.1

Medical condition in easily understood language

diabetic macular edema

E.1.1.2

Therapeutic area

Diseases [C] - Eye Diseases [C11]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10057934
E.1.2	Term	Diabetic macular edema
E.1.2	System Organ Class	100000004853

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 safety, tolerability, and efficacy, in reference to Lucentis® monotherapy, of three q4w intravitreal (IVT) doses of LKA651 in treating DME when administered as monotherapy and in combination with Lucentis®

E.2.2

Secondary objectives of the trial

- To evaluate the serum pharmacokinetic (PK) profile of total LKA651 and Lucentis® following three q4w IVT doses of LKA651, or a combination of LKA651 and Lucentis,® in patients with DME

- To evaluate duration of effect of three q4w IVT doses of LKA651 in patients with DME.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Male and female patients age 18 to 90 years of age inclusive
• Diagnosis of type I or type II diabetes mellitus.
• The Early Treatment Diabetic Retinopathy Study (ETDRS) letter score in the study eye must be between 24 and 72 letters inclusive (approximate Snellen equivalent of 20/40-20/320). The non-study eye (fellow eye) should be ≥34 letters or better (approximate Snellen equivalent of 20/200) at screening
• Presence of DME in the study eye, with decrease in vision due to foveal thickening of central macular thickness ≥ 320µm in the central subfield, as assessed on spectral-domain ocular coherence tomography (SD-OCT) and confirmed by the central reading center at screeening
• Sufficiently clear ocular media and adequate pupil dilation in the study eye to permit fundus photographs of adequate clarity to measure diameters of retinal arteries and veins at screening

Please refer to the protocol for a comprehensive list of inclusion criteria

E.4

Principal exclusion criteria

Patient with history of treatment for DME in the study eye as defined
by the following:
- IVT anti-vascular endothelial growth factor (VEGF) treatment within 90
days before baseline in the study eye. History or concurrent treatment
with these medications/procedures in the non study eye is permitted.
- Patient with history of intraocular corticosteroids in the study eye
including dexamethasone intravitreal implants during the 6 month
period prior to baseline. Any prior use of fluocinolone acetonide intravitreal implant (Iluvien) is prohibited regardless of timing.
• Concomitant conditions or ocular disorders in the study eye which may, in the opinion of the investigator, confound the interpretation of study results, compromise visual acuity or require medical or surgical intervention during the study period:
- High risk proliferative diabetic retinopathy in the study eye, as per investigator assessment at both screening and baseline.
- Patients with the following conditions in the study eye at screening or baseline must be excluded: structural damage of the fovea, vitreous hemorrhage, retinal detachment, vitreomacular traction, macular hole, retinal vein/arterial occlusion, neovascularization of iris or choroidal neovascularization of any cause)
3. Laser photocoagulation (macular or panretinal) in the study eye during the 3-month period prior to baseline.
• Patients, with type 1 or type 2 diabetes who have a hemoglobin A1C
≥ 12% at screening.
• Any progressive disease of the retina in the study eye (e.g. uveitis,
rod-cone dystrophy) or optic nerve other than those listed in the
inclusion criteria.
• Area of retinal ischemia involving the macula (as measured by the
foveal avascular zone) ≥ 1000 μm in linear diameter.
• Active intraocular inflammation (graded as trace or above) in either
eye or active intraocular infection in the study eye.
• Active infection involving the study eye's ocular adnexa including
infectious conjunctivitis, keratitis, scleritis, endophthalmitis, as well as
idiopathic or
autoimmune-associated uveitis in either eye, or intraocular infection in
either eye.
• Any intraocular surgery (except uncomplicated cataract surgery) in the study eye within the past 6 months preceding Day 1. Uncomplicated cataract surgery (e.g. routine surgery with no intra or post operative complications) within the past 3 months preceding Day 1. Yttrium-Aluminum-Garnet (YAG) laser capsulotomy within the past 30 days preceding baseline.
• Current diagnosis of clinically significant anemia, or hemoglobin <10
g/dL for women and <11 g/dL for men.
Please refer to the protocol for a comprehensive list of exclusion criteria

E.5 End points

E.5.1

Primary end point(s)

1) Best Corrected Visual Acuity (BCVA) as assessed by ETDRS (Early Treatment Diabetic Retinopathy Study) visual acuity charts at week 12.

2) Central subfield retinal thickness as measured by SD-OCT at week 12

3) Ocular and systemic AEs - are evaluated on 1,15,43,85,113,141 and 169 days.

4) Vital signs are evaluated on blood pressure and heart rate -1,29,57,85,113,141 and 169 days
ECG intervals - 1 and 169 days

5) Safety laboratory measures (including reticulocyte count) are evaluated on 1,29,57,85 and 169 days

6) Complete ophthalmic exam is evaluated on :
• IOP - 1,29,57,85,113,141 and 169 days
• BCVA - 1,29,57,85,113,141 and 169 days
• Macular thickness by SD-OCT - 1,29,57,85,113,141 and 169 days
• FA - 85 and 169 days

E.5.1.1

Timepoint(s) of evaluation of this end point

1) Best Corrected Visual Acuity as assessed by ETDRS visual acuity charts - week 12.

2) Central subfield retinal thickness as measured by SD-OCT - week 12

3 )Ocular and systemic AEs - are evaluated on 1,15,43,85,113,141 and 169 days

4) Vital signs are evaluated on blood pressure and heart rate -1,29,57,85,113,141 and 169 days
ECG intervals - 1 and 169

5) Safety laboratory measures (including reticulocyte count) are evaluated on 1,29,57,85 and 169

6) Complete ophthalmic exam is evaluated
• IOP - 1,29,57,85,113,141 and 169 days
• BCVA - 1,29,57,85,113,141 and 169 days
• Macular thickness by SD-OCT - 1,29,57,85,113,141 and 169 days
• FA - 85 and 169 days

E.5.2

Secondary end point(s)

1) Time to retreatment with anti-VEGF (as determined by PI) after week 12 during an additional 12-week extension phase

2) Serum levels of total LKA651 (Maximum concentration (Cmax) and Area under the curve (AUC)0-28d in monotherapy or in combination with Lucentis® after the first dose

3) Serum levels of ranibizumab (Cmax and AUC0-28d) when administered in combination with LKA651 after the first dose

4) Patients with 2 and ≥3 step improvement in the diabetic retinopathy severity scale by color fundus photos at week 12 and week 24

E.5.2.1

Timepoint(s) of evaluation of this end point

to 1) Time to retreatment with anti-VEGF (as determined by PI) after week 12 during an additional 12-week extension phase - week 12 and week 24

2) Serum levels of total LKA651 (Maximum concentration (Cmax) and Area under the curve (AUC)0-28d in monotherapy or in combination with Lucentis® after the first dose - day 29

3) Serum levels of ranibizumab (Cmax and AUC0-28d) when administered in combination with LKA651 after the first dose - day 29

4) Patients with 2 and ≥3 step improvement in the diabetic retinopathy severity scale by color fundus photos - week 12 and week 24

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

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)

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

United States

Spain

Germany

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 - see protocol

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)

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

2019-01-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-04-11

P. End of Trial
P.	End of Trial Status	Completed

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