Clinical Trials Register

Summary
EudraCT Number:	2013-003017-18
Sponsor's Protocol Code Number:	OPH1003
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2013-09-24
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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2013-003017-18

A.3

Full title of the trial

A phase 3 randomized, double-masked, controlled trial to establish the safety and efficacy of intravitreous administration of Fovista™ (anti PDGF-b pegylated aptamer) administered in combination with Lucentis® compared to Lucentis® monotherapy in subjects with subfoveal neovascular age-related macular degeneration

III. fázisú, randomizált, kettős vak, kontrollált vizsgálat az intravitreálisan, Lucentis®-szel kombinációban adott Fovista™ (Anti PDGF-B pegilált aptamer) biztonságosságának és hatékonyságának megállapítására az önmagában adott Lucentis®-szel összehasonlítva szubfoveális neovaszkuláris, korral járó makuladegenerációban szenvedő betegeken.

A.3.1

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

Clinical trial to establish the safety and efficacy of intravitreous administration of Fovista™ administered in combination with Lucentis® compared to Lucentis® administered alone in subjects with subfoveal neovascular age-related macular degeneration

Klinikai vizsgálat a Lucentis®-szel kombinációban intravitreálisan adott Fovista™ biztonságosságának és hatékonyságának megállapítására az önmagában adott Lucentis®-szel összehasonlítva szubfoveális neovaszkuláris időskori makuladegenerációban szenvedő betegeknél.

A.4.1

Sponsor's protocol code number

OPH1003

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	OPHTHOTECH CORPORATION
B.1.3.4	Country	United States
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	OPHTHOTECH CORPORATION
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	OPHTHOTECH CORPORATION
B.5.2	Functional name of contact point	Satish Tripathi
B.5.3	Address:
B.5.3.1	Street Address	One Penn Plaza – 19th Floor
B.5.3.2	Town/ city	New York
B.5.3.3	Post code	NY 10119
B.5.3.4	Country	United States
B.5.4	Telephone number	+1609606 6348
B.5.5	Fax number	+1609452 7435
B.5.6	E-mail	satish.tripathi@ophthotech.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	Fovista
D.3.2	Product code	E10030
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	Fovista
D.3.9.1	CAS number	1449390-73-1
D.3.9.2	Current sponsor code	E10030
D.3.9.3	Other descriptive name	E10030
D.3.9.4	EV Substance Code	SUB126298
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: 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 10 mg/ml solution for injection
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.3.4	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.3.9.4	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	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

Subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD).

Időskori makuladegeneráció (AMD) nyomán kialakult szubfoveális chorioideális neovaszkularizáció.

E.1.1.1

Medical condition in easily understood language

Subfoveal choroidal neovascularization in addition to age-related macular degeneration

Időskori makuladegeneráció mellett kialakult szubfoveális chorioideális neovaszkularizáció.

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	18.1
E.1.2	Level	PT
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	18.1
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

The objectives of this study are to evaluate the safety and efficacy of Fovista™ intravitreous administration when administered in combination with Lucentis® compared to Lucentis® monotherapy in subjects with subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD).

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

A Pharmacogenetic substudy in subjects enrolled in protocoll OPH1003 with neovascular age-related macular degeneration
Final version date: 27 January 2015

Only in several countries: USA, France, and Hungary

E.3

Principal inclusion criteria

Ophthalmic Inclusion Criteria
The following inclusion criteria apply to the study eye:
•Active subfoveal choroidal neovascularization (CNV) due to AMD with some classic component (i.e., predominantly classic or minimally classic) as documented by fluorescein angiogram.
•Best corrected visual acuity in the study eye between 20/63 and 20/200, inclusive. The VA must be re-confirmed at Day 1 prior to randomization.
•Total area of the lesion (including blood, neovascularization, and scar/atrophy) must be ≤ 7 disc areas (DA), of which at least 50% must be active CNV. Active CNV is defined as leakage on fluorescein angiogram within the anatomic fovea AND/OR subretinal or intraretinal fluid on OCT within the central 1 mm subfield.
•Presence on OCT of subretinal hyper-reflective material (SHRM) within the central 1 mm subfield; SHRM is defined as hyper-reflective material located external to the outer retina and internal to the RPE, or, when the RPE is not well defined, internal to Bruch's membrane.
•Clear ocular media and adequate pupillary dilatation to allow collection of fundus photographs and fluorescein angiograms of a sufficient quality to be analyzed by the central reading center.
•Intraocular pressure (IOP) of 21 mmHg or less.

General Inclusion Criteria
•Subjects of either gender aged ≥ 50 years.
•Performance Status ≤ 2 according to Eastern Cooperative Oncology Group (ECOG) / World Health Organization (WHO) scale.
•Women must agree to be using two forms of effective contraception, be post-menopausal for at least 12 months prior to trial entry, or surgically sterile; if of child-bearing potential, a serum pregnancy test must be performed within 14 days prior to the first injection with a negative result. The two forms of effective contraception must be implemented during the trial and for at least 60 days following the last dose of test medication.
•Provide written informed consent.
•Ability to comply with study and follow-up procedures and return for all trial visits.

E.4

Principal exclusion criteria

Ophthalmic Exclusion Criteria
•Any prior treatment for AMD in the study eye prior to the Day 1 visit, except oral supplements of vitamins and minerals.
•Any prior intravitreal treatment in the study eye prior to the Day 1 visit, regardless of indication (including intravitreal corticosteroids).
•More than 50% of the total lesion size made up of scarring or atrophy as determined by fundus photography with or without fluorescein angiography, with or without OCT. Subjects with any subfoveal scar or subfoveal atrophy directly below the center of the fovea are excluded.
•More than 50% of the total lesion size consisting of subretinal hemorrhage.
•Presence of retinal angiomatous proliferation (RAP).
•Presence of significant serous pigment epithelial detachments (PEDs), such as large PEDs that constitute greater than 50% of the total lesion or have a vertical height of ≥ 400 μm. Presence of pure PED without subretinal hyper-reflective material.
•Presence of pigment epithelial tears or rips.
•Presence of intraocular inflammation (≥ trace cell or flare), significant epiretinal membrane (causing distortion of macular anatomy and/or opacification), significant vitreomacular traction (causing distortion of macular anatomy), macular hole (full or partial thickness) or vitreous hemorrhage.
•Aphakia or absence of the posterior capsule. Absence of an intact posterior capsule is allowed if it occurred as a result of YAG laser posterior capsulotomy in association with prior posterior chamber IOL implantation.
•History of idiopathic or autoimmune-associated uveitis in either eye.
•Significant media opacities, including cataract, which might interfere with visual acuity, assessment of toxicity, or fundus photography in the study eye. Subjects should not be entered if there is likelihood that they will require cataract surgery in the study eye in the next 12 months.
•Presence of other causes of choroidal neovascularization, including pathologic myopia (spherical equivalent of -8 diopters or more, or axial length of 25mm or more), the ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, and multifocal choroiditis.
•Any intraocular surgery or thermal laser within three (3) months of trial entry. Any prior thermal laser in the macular region, regardless of indication.
•Any ocular or periocular infection in the past twelve (12) weeks.
•History of any of the following conditions or procedures in the study eye: Rhegmatogenous retinal detachment, pars plana vitrectomy, filtering surgery (e.g. trabeculectomy), glaucoma drainage device, corneal transplant.
•Previous therapeutic radiation in the region of the study eye.

General Exclusion Criteria
•Any of the following underlying conditions or diseases including:
A definitive diagnosis of diabetes mellitus or diabetic retinopathy (regardless of HbA1c level)
HbA1c value of ≥ 6.5%*
*If the HbA1c value is ≥ 6.5% and ≤ 6.9%, and the patient has no signs or symptoms of diabetes mellitus, has a normal creatinine, has no diabetic retinopathy and no glycosuria, then the patient may have an oral glucose tolerance test (OGTT) at the discretion of the investigator. If the 2-hour glucose value on OGTT is <200 mg/dL (<11.1 mmol/L), then the patient may be enrolled.
History of other disease, metabolic dysfunction, physical examination finding or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk for treatment complications.
History or evidence of severe cardiac disease (e.g., NYHA
Functional Class III or IV - see Appendix 17.6), history or clinical evidence of unstable angina, acute coronary syndrome, myocardial infarction or coronary artery revascularization within 6 months, or ventricular tachyarrythmias requiring ongoing treatment.
Stroke (within 12 months of trial entry).
Any major surgical procedure within one month of trial entry.
•Any treatment with an investigational agent in the 60 days prior to randomization for any condition.
•Known serious allergies to the fluorescein dye used in angiography (mild allergy amenable to treatment is allowable), or to the components or formulation of either Fovista™ or Lucentis®.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is the mean change in visual acuity (ETDRS letters) from baseline at the Month 12 visit.

E.5.1.1

Timepoint(s) of evaluation of this end point

Following Month 12 visit

E.5.2

Secondary end point(s)

The proportion of subjects in each treatment group gaining 20 or more ETDRS letters from baseline at the Month 12 visit.
The proportion of subjects in each treatment group gaining 25 or more ETDRS letters from baseline at the Month 12 visit.
The proportion of subjects in each treatment group losing 5 or more ETDRS letters from baseline at the Month 12 visit.
The mean change in visual acuity (ETDRS letters) from baseline at the Month 6 visit.

E.5.2.1

Timepoint(s) of evaluation of this end point

Following Month 6 and 12 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

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)

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

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Fovista and sham administered by an unmasked 1st Investigator, 2nd Investigator blinded

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

Fovista sham as an empty vial

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

Colombia

Denmark

France

Germany

Hungary

Israel

Spain

Turkey

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

Last visit of the last subject

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:

155

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

500

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

200

F.4.2

For a multinational trial

F.4.2.1

In the EEA

231

F.4.2.2

In the whole clinical trial

655

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)

Standard of care.

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

2013-11-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-11-13

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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