Clinical Trials Register

Summary
EudraCT Number:	2020-004736-24
Sponsor's Protocol Code Number:	OPT-302-1004
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2021-08-30
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2020-004736-24

A.3

Full title of the trial

A Phase 3, Multicentre, Double-masked, Randomised Study to Evaluate the Efficacy and Safety of Intravitreal OPT-302 in Combination with Ranibizumab, Compared with Ranibizumab Alone, in Participants with Neovascular Age-related Macular Degeneration (nAMD)

Studio di fase 3, multicentrico, in doppio cieco, randomizzato, per valutare l’efficacia e la sicurezza di OPT-302 intravitreale in combinazione con ranibizumab, rispetto a ranibizumab in monoterapia, in pazienti affetti da degenerazione maculare neovascolare legata all’età (DMLE)

A.3.1

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

A clinical study of OPT-302 with ranibizumab compared to ranibizumab alone in patients with neovascular age-related macular degeneration

Uno studio clinico di OPT-302 con ranibizumab rispetto a ranibizumab in monoterapia in pazienti affetti da degenerazione maculare neovascolare

A.3.2

Name or abbreviated title of the trial where available

ShORe

A.4.1

Sponsor's protocol code number

OPT-302-1004

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04757610

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	OPTHEA LIMITED
B.1.3.4	Country	Australia
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	Opthea Limited
B.4.2	Country	Australia
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Opthea Limited
B.5.2	Functional name of contact point	Clinical Development Director
B.5.3	Address:
B.5.3.1	Street Address	Suite 0403, Level 4, 650 Chapel Street
B.5.3.2	Town/ city	South Yarra
B.5.3.3	Post code	VIC 3141
B.5.3.4	Country	Australia
B.5.4	Telephone number	0061398260399
B.5.6	E-mail	clare.price@opthea.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	OPT-302
D.3.2	Product code	[OPT-302]
D.3.4	Pharmaceutical form	Solution for injection/infusion
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	Vascular endothelial growth factor receptor-3 (VEGFR-3) derivative fused to a human immunoglobulin (IgG)1 Fc fragment (no proposed INN at this stage)
D.3.9.2	Current sponsor code	OPT-302
D.3.9.4	EV Substance Code	SUB191360
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	40
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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 in pre-filled syringe
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited, Ireland EU/1/06/374/003
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom (Northern Ireland)
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
D.3.2	Product code	[na]
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
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.3.9.4	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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	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 (wet AMD)

Degenerazione maculare neovascolare legata all’età (DMLE)

E.1.1.1

Medical condition in easily understood language

Chronic eye disease that causes blurred vision or a blind spot in one´s visual field caused by abnormal blood vessels leaking fluid or blood into the part of the retina responsible for central vision

Malattia cronica occhi causa visione offuscata o punto cieco in un campo visivo causato da vasi sang normali che fuoriescono fluido o sangue nella parte della retina responsabile della vis centrale

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	20.0
E.1.2	Level	SOC
E.1.2	Classification code	10015919
E.1.2	Term	Eye disorders
E.1.2	System Organ Class	10015919 - Eye disorders

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	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	20.1
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

To determine the efficacy of intravitreal 2.0 mg OPT-302 when administered in combination with intravitreal 0.5 mg ranibizumab, in participants with neovascular AMD.

Determinare l’efficacia di 2,0 mg di OPT-302 intravitreale somministrato in combinazione con 0,5 mg di ranibizumab intravitreale, in partecipanti con AMD neovascolare.

E.2.2

Secondary objectives of the trial

The secondary objectives of the study are to determine the effects of intravitreal 2.0 mg OPT-302 when administered in combination with intravitreal 0.5 mg ranibizumab from Baseline to (and at) Week 52 as determined by:
Efficacy:
• Changes in ETDRS BCVA letter score
• Changes in anatomical parameters (CNV area, CST, SRF and IR cysts)
• Changes in National Eye Institute 25-item Vision Function Questionnaire (NEI-VFQ-25) Participant Reported Outcomes (PROs).
Safety:
• Incidence of adverse events (AEs)
• Deterioration in ETDRS BCVA letter score
• Incidence of ADA formation
Pharmacokinetic:
• Pharmacokinetic parameters of OPT-302.

Determinare gli effetti dell’aggiunta di 2,0 mg di OPT-302 intravitreale a 0,5 mg di ranibizumab intravitreale dal Basale fino alla (e alla) Settimana 52 in termini di:
Efficacia:
• Variazioni nel punteggio della massima acuità visiva corretta (BCVA) misurata con la scala ETDRS (Early Treatment Diabetic Retinopathy Study) per le lettere
• Cambiamenti nei parametri anatomici (area di neovascolarizzazione coroideale [CNV], spessore del sottocampo centrale [CST], fluido sottoretinico [SRF] e cisti intraretiniche [IR])
• Cambiamenti negli esiti riferiti dal paziente (PRO) nel questionario sulla funzione visiva a 25 domande del National Eye Institute (NEI-VFQ-25)
Sicurezza:
• Incidenza di eventi avversi (EA)
• Peggioramento del punteggio della BCVA misurata con la scala ETDRS per le lettere
• Incidenza della formazione di anticorpi anti-OPT-302 (ADA)
Farmacocinetica:
• Farmacocinetica di OPT-302.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Male or female participants at least 50 years of age.
• Active subfoveal CNV lesion or juxtafoveal CNV lesion with foveal involvement that is secondary to AMD in the Study Eye.
• An ETDRS BCVA score between 60 and 25 (inclusive) letters in the Study Eye.

• Partecipanti maschi o femmine di almeno 50 anni di età.
• Lesione CNV subfoveale attiva o lesione CNV iuxtafoveale con coinvolgimento foveale secondario all’AMD nell’occhio in studio.
• Un punteggio di BCVA all’ETDRS compreso tra 60 e 25 lettere (incluse) per l’occhio in studio.

E.4

Principal exclusion criteria

Study Eye:
• Any previous treatment for neovascular AMD.
• Clinically significant ocular disorders (other than neovascular AMD), which may, in the investigator’s opinion, interfere with assessment of BCVA, assessment of safety, or fundus imaging.
• Any current (or history of a) social, psychological, or medical condition that precludes enrolment into the study.

Note: other protocol exclusion criteria may also apply.

Occhio in studio:
• Qualsiasi trattamento precedente per AMD neovascolare
• Disturbi oculari clinicamente significativi (diversi dall’AMD neovascolare) che, a giudizio dello sperimentatore, possono interferire con la valutazione della BCVA, la valutazione della sicurezza o le immagini del fondo oculare.
• Qualsiasi infezione oculare o perioculare in corso

NOTE: possono applicarsi anche altri criteri di esclusione del protocollo.

E.5 End points

E.5.1

Primary end point(s)

Mean change in Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) letters from Baseline to Week 52

Variazione media dal basale alla settimana 52 della BCVA, misurata con la scala ETDRS per le lettere

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 52

Settinama 52

E.5.2

Secondary end point(s)

Efficacy:
• Proportion of participants gaining 10 or more Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) letters from Baseline to Week 52
• Proportion of participants gaining 15 or more Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) letters from Baseline to Week 52
• Proportion of participants with absence of both sub-retinal fluid (SRF) and intra-retinal (IR) cysts by SD-OCT at Week 52
• Change in choroidal neovascularisation (CNV) area by fluorescein angiography (FA) from Baseline to Week 52
• Change in central sub-field thickness (CST) by spectral domain optical coherence tomography (SD-OCT) from Baseline to Week 52
• Change in National Eye Institute 25-question visual function questionnaire (NEI VFQ-25) composite score from Baseline to Week 52
• Change in mean composite score of 25 questions. A higher mean change means an overall improvement in visual function.

Efficacia
• Percentuale di partecipanti che ottengono un punteggio di 10 o più di BCVA all’ETDRS sulle lettere dal basale alla settimana 52
• Percentuale di partecipanti che ottengono un punteggio di 15 o più della BCVA all’ETDRS sulle lettere dal basale alla settimana 52
• Percentuale di partecipanti con assenza di cisti sia SRF sia IR mediante tomografia a coerenza ottica nel dominio spettrale (SD-OCT) alla settimana 52
• Variazione dell’area CNV misurata mediante angiografia con fluoresceina (FA) dal basale alla settimana 52
• Variazione del CST rilevata da SD-OCT dal basale alla settimana 52
• Variazione del punteggio composito al questionario NEI VFQ-25 dal basale alla settimana 52

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 52

Settimana 52

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

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

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

Iniezione sham

Sham Injection

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

Information not present in EudraCT

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

Australia

Brazil

Canada

India

Israel

Korea, Republic of

Malaysia

Russian Federation

Thailand

Ukraine

United States

Bulgaria

Denmark

France

Germany

Hungary

Italy

Latvia

Poland

Spain

United Kingdom

Czechia

Argentina

Greece

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

LPLV

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:

100

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

890

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

276

F.4.2.2

In the whole clinical trial

990

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)

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

2021-08-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-05-27

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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