Clinical Trials Register

Summary
EudraCT Number:	2012-003763-22
Sponsor's Protocol Code Number:	BAY73-4506/15984
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2014-06-10
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

Czechia - SUKL

A.2

EudraCT number

2012-003763-22

A.3

Full title of the trial

A combined Phase IIa / IIb study of the efficacy, safety, and tolerability of repeated topical doses of regorafenib eye drops, in treatment-naïve subjects with neovascular age related macular degeneration

A.3.1

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

Study of the efficacy, safety and tolerability of repeated administration of eye drops containing regorafenib in newly diagnosed patients with "wet" or
neovascular ("new blood vessel growth") Age-Related Macular Degeneration (wet AMD).

Kombinovaná studie fáze IIa/IIb účinnosti, bezpečnosti a snášenlivosti opakovaných dávek očních kapek regorafenibu u dosud neléčených subjektů s věkem podmíněnou neovaskulární makulární degenerací.

A.3.2

Name or abbreviated title of the trial where available

Regorafenib eye drops: Investigation of efficacy and safety in wet AMD

A.4.1

Sponsor's protocol code number

BAY73-4506/15984

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	Bayer HealthCare Aktiengesellschaft
B.1.3.4	Country	Germany
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	Bayer HealthCare Aktiengesellschaft
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bayer HealthCare Aktiengesellschaft
B.5.2	Functional name of contact point	Clinical Trials Contact
B.5.3	Address:
B.5.3.1	Street Address	CTP Team / Ref: "EU CTR" / Bayer Pharma AG
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	13342
B.5.3.4	Country	Germany
B.5.4	Telephone number	49 30 300139003
B.5.6	E-mail	clinical-trials-contact@bayerhealthcare.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	Regorafenib (BAY 73-4506) eye drops; 2% (w/v)
D.3.2	Product code	BAY 73-4506
D.3.4	Pharmaceutical form	Eye drops, suspension
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Ocular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	REGORAFENIB
D.3.9.1	CAS number	1019206-88-2
D.3.9.2	Current sponsor code	BAY 73-4506
D.3.9.3	Other descriptive name	Regorafenib monohydrate
D.3.9.4	EV Substance Code	SUB73090
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	20
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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Regorafenib (BAY 73-4506) eye drops; 3% (w/v)
D.3.2	Product code	BAY 73-4506
D.3.4	Pharmaceutical form	Eye drops, suspension
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Ocular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	REGORAFENIB
D.3.9.1	CAS number	1019206-88-2
D.3.9.2	Current sponsor code	BAY 73-4506
D.3.9.3	Other descriptive name	Regorafenib monohydrate
D.3.9.4	EV Substance Code	SUB73090
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	30
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: 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	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	Ranibizumab (Lucentis)
D.3.2	Product code	NA
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	NA
D.3.9.3	Other descriptive name	RANIBIZUMAB
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	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	Eye drops
D.8.4	Route of administration of the placebo	Ocular use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Injection
D.8.4	Route of administration of the placebo	Intravitreal use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

neovascular age related macular degeneration

E.1.1.1

Medical condition in easily understood language

"wet” or neovascular (“new blood vessel growth”) Age-Related Macular Degeneration (wet AMD)

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	17.1
E.1.2	Level	PT
E.1.2	Classification code	10064930
E.1.2	Term	Age-related macular degeneration
E.1.2	System Organ Class	10015919 - Eye disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.1
E.1.2	Level	LLT
E.1.2	Classification code	10071129
E.1.2	Term	Neovascular age-related macular degeneration
E.1.2	System Organ Class	10015919 - Eye disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.1
E.1.2	Level	PT
E.1.2	Classification code	10025409
E.1.2	Term	Macular degeneration
E.1.2	System Organ Class	10015919 - Eye disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.1
E.1.2	Level	LLT
E.1.2	Classification code	10067791
E.1.2	Term	Wet macular degeneration
E.1.2	System Organ Class	10015919 - Eye disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Assess the effect of treatment with regorafenib eye drops on visual acuity at Study Week 4 and at Study Week 12 in subjects with subfoveal choroidal neovascularization due to age related macular degeneration.
For Part B: in addition, explore an optimal dosing regimen

E.2.2

Secondary objectives of the trial

Evaluate the effect of treatment with regorafenib eye drops on ocular safety and tolerability

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Signed informed consent
• Men and women ≥ 50 years of age
• Active primary subfoveal choroidal neovascularization lesions secondary to age related macular degeneration, including juxtafoveal lesions that affect the fovea as evidenced by fluorescein angiography in the study eye and reviewed by the central reading center
• The area of choroidal neovascularization must occupy at least 50% of total lesion in the study eye, as determined by fluorescein angiography review at the central reading center
• Evidence of intraretinal and/or subretinal fluid on OCT and reviewed by the central reading center
• Early Treatment Diabetic Retinopathy Study best corrected visual acuity of 73 to 25 letters (20/40 to 20/320 Snellen equivalent) in the study eye
• Willing, committed, and able to return for all clinic visits and complete all study related procedures
Subjects who participate in Part A of the protocol are ineligible for Part B.

E.4

Principal exclusion criteria

1.Concurrent disease in the study eye, other than AMD (e.g., corneal diseases and dystrophies, conjunctival diseases, eye lid abnormalities, or any other diseases of the cornea and macula, or optic nerve abnormality) that could compromise visual acuity, likely require medical or surgical intervention during the study period, would limit the potential to gain or lose vision during study treatment, or could otherwise confound interpretation of the results
2.Any findings in the study eye that would limit the potential to benefit from study treatment, or could otherwise confound interpretation of the results such as total lesion size (including structural damage to the center of macula, neovascularization, scar, blood) > 12 disc areas (30.5 mm2) and subfoveal fibrosis as assessed by FA
3.Only one functional eye, even if that eye is otherwise eligible for the study
4.Prior ocular or systemic treatment or surgery for neovascular AMD in the study eye except dietary supplements or vitamins
5.Prior treatment with any systemic anti-VEGF agent
12.History or current use of long-acting steroids, either systemically or injected intraocularly, periocularly, subconjunctivally
15. Intraocular pressure ≥ 25 millimeters of mercury (mmHg) in the study eye as well as uncontrolled glaucoma
16. Any other condition that would require frequent chronic coadministration of other topical eye medications that would interfere with study drug administration
17. Symptoms or conditions consistent with contraindications listed in the current local label for ranibizumab
18. Participation in an investigational study within 30 days prior to start of study treatment that involved treatment with any drug (excluding vitamins and minerals) or device
27.Lactating women and women of child-bearing potential with either a positive pregnancy test result or no pregnancy test at s are excluded. Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of child bearing potential. For more please
refer to protocol.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy variables in both Part A and Part B are the mean change
from baseline in best corrected visual acuity as measured by Early Treatment
Diabetic Retinopathy Study letter score at Study Week 4 and Study Week 12.

E.5.1.1

Timepoint(s) of evaluation of this end point

Study Week 4 and Study Week 12

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

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

Yes

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

Therapy, Safety and Efficacy for both parts; additionally, dose response for part B only

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

Yes

E.8.1.7.1

Other trial design description

Part A: single-arm, open-label design Part B: double-masked, active-controlled

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

Yes

E.8.2.3.1

Comparator description

Comparator: other medicinal product and placebo only for part B

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

Argentina

Australia

Austria

Canada

Chile

Colombia

Czech Republic

France

Germany

Hong Kong

Hungary

Israel

Italy

Japan

Korea, Republic of

Poland

Slovakia

Spain

Switzerland

United States

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

For each participating EU country, the end of the study according to the EU Clinical Trial Directive will be reached when the last visit of the last subject for all centers in the respective country has occurred.

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:

445

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

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Most common reasons for incapability of giving consent personally, is being unable to read due to visual impairment caused by the disease. Please refer to page 71 of 94 Am1

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

195

F.4.2.2

In the whole clinical trial

540

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)

No post-study therapy (after the 12-week treatment and 4-week follow-up periods) is planned for this trial. At the EOS visit for each part of the study (Ph II Part A and Ph II Part B), subjects will be advised to consult with their ophthalmologist regarding appropriate ongoing treatment for their AMD.

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

2014-09-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-09-11

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2015-07-16

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