Clinical Trials Register

Summary
EudraCT Number:	2019-001506-17
Sponsor's Protocol Code Number:	THR-149-002
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-01-21
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

2019-001506-17

A.3

Full title of the trial

A Phase 2, randomised, multicentre study to assess the dose level of multiple THR-149 injections and to evaluate the efficacy and safety of THR-149 versus aflibercept for the treatment of diabetic macular oedema (DME)

Studio multicentrico, randomizzato, di fase II, allo scopo di valutare il dosaggio di iniezioni multiple di THR-149 e di valutare l’efficacia e la sicurezza di THR-149 rispetto ad aflibercept nel trattamento dell’edema maculare diabetico (EMD)

A.3.1

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

A study to evaluate THR-149 treatment for diabetic macular oedema

Uno studio per valutare il trattamento dell’edema maculare diabetico con THR-149

A.3.2

Name or abbreviated title of the trial where available

KALAHARI

A.4.1

Sponsor's protocol code number

THR-149-002

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	OXURION NV
B.1.3.4	Country	Belgium
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	Oxurion NV
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Oxurion NV
B.5.2	Functional name of contact point	Global Clinical Development
B.5.3	Address:
B.5.3.1	Street Address	Gaston Geenslaan 1
B.5.3.2	Town/ city	Leuven
B.5.3.3	Post code	B-3001
B.5.3.4	Country	Belgium
B.5.4	Telephone number	16751310
B.5.5	Fax number	16751311
B.5.6	E-mail	info@oxurion.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	THR-149
D.3.2	Product code	[THR-149]
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	THR-149
D.3.9.2	Current sponsor code	THR-149
D.3.9.4	EV Substance Code	SUB191889
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2600
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	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	Eylea 40 mg/ml solution for injection
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer AG
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	Aflibercept
D.3.2	Product code	[.]
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	AFLIBERCEPT
D.3.9.1	CAS number	862111-32-8
D.3.9.2	Current sponsor code	.
D.3.9.4	EV Substance Code	SUB26987
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	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 Oedema (DME)

Edema Maculare Diabetico (EMD)

E.1.1.1

Medical condition in easily understood language

Diabetic macular oedema is a swelling in the light-sensitive tissue in the back of the eye (called the retina) in people with diabetes, caused by leaking of blood vessels.

L'edema maculare diabetico è un gonfiore del tessuto sensibile alla luce nella parte posteriore dell'occhio (chiamato retina) in persone con diabete, causato da perdite di liquidi dai vasi sanguigni.

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	10057915
E.1.2	Term	Diabetic macular oedema
E.1.2	System Organ Class	100000004853

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

The objective of the study is to select the THR-149 dose and to assess the difference in treatment effect between THR-149 and aflibercept in terms of increase in best corrected visual acuity (BCVA) from Baseline at Month 3.

L'obiettivo di questa parte dello studio è determinare il dosaggio di THR-149 e di valutare la differenza nel trattamento tra THR-149 e aflibercept in termini di aumento dell'acuità visiva (BCVA) migliore corretta rispetto al basale al mese 3.

E.2.2

Secondary objectives of the trial

• To assess the efficacy of 3 monthly intravitreal injections of THR-149 over-time
• To assess the safety of 3 monthly intravitreal injections of THR-149 over-time

• Valutare l'efficacia di 3 iniezioni intravitreali mensili di THR-149 nel tempo
• Valutare la sicurezza di 3 iniezioni intravitreali mensili di THR-149 nel tempo

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Written informed consent obtained from the subject prior to screening procedures
• Male or female aged 18 years or older at the time of signing the informed consent
• Type 1 or type 2 diabetes
• BCVA ETDRS letter score = 73 and = 39 in the study eye
• CI-DME with CST of = 320µm in men or = 305µm in women, on Spectralis SD-OCT in the study eye
• BCVA ETDRS letter score = 34 in the fellow eye
• Received = 5 anti-VEGF injections for the treatment of CI-DME

• Consenso informato scritto ottenuto dall soggetto prima delle procedure di screening
• Maschio o femmina di età pari o superiore a 18 anni al momento della firma del consenso informato
• Diabete di tipo 1 o di tipo 2
• Miglior acuità visiva corretta (BCVA) con punteggio ETDRS in lettere = 73 e = 39 nell'occhio in studio
• CI-DME con CST di = 320µm negli uomini o = 305µm nelle donne, su Spectralis SD-OCT nell'occhio in studio
• Miglior acuità visiva corretta (BCVA) con punteggio ETDRS in lettere = 34 per l'altro occhio
• Ricevuto = 5 iniezioni anti-VEGF per il trattamento di CI-DME

E.4

Principal exclusion criteria

• Macular oedema due to causes other than DME in the study eye
• Concurrent disease in the study eye, other than DME, that could require medical or surgical intervention during the study period or could confound interpretation of the results
• Any condition in the study eye that could confound the ability to detect the efficacy of the IMP
• Presence of neovascularisation at the disc in the study eye
• Presence of iris neovascularisation in the study eye
• previous confounding medications / interventions, or their planned administration
• Uncontrolled glaucoma in the study eye
• Any active or suspected ocular or periocular infection, or active intraocular inflammation, in either eye
• Previously received THR-149 in either eye
• Untreated diabetes
• Glycated haemoglobin A (HbA1c) > 12%
• Uncontrolled hypertension

• Edema maculare dovuto a cause diverse dal DME nell'occhio dellostudio
• Malattia concomitante nell'occhio dello studio, diversa dalla DME, che potrebbe richiedere un intervento medico o chirurgico durante il periodo di studio o potrebbe confondere l'interpretazione dei risultati
• Qualsiasi condizione nell'occhio in studio che potrebbe confondere la capacità di rilevare l'efficacia dell'IMP
• Presenza di neovascolarizzazione al disco nell'occhio dello studio
• Presenza di neovascolarizzazione dell'iride nell'occhio dello studio
• precedenti farmaci / interventi confondenti già effettuati o pianificati
• Glaucoma incontrollato nell'occhio dello studio
• Qualsiasi infezione oculare o perioculare attiva o sospetta o infiammazione intraoculare attiva in entrambi gli occhi
• Precedente trattamento con THR-149 in entrambi gli occhi
• Diabete non trattato
• Emoglobina glicata A (HbA1c)> 12%

E.5 End points

E.5.1

Primary end point(s)

Mean change in BCVA ETDRS letter score from Baseline, at Month 3

Variazione media del punteggio ETDRS in lettere per la BCVA dal Basale al Mese 3

E.5.1.1

Timepoint(s) of evaluation of this end point

From first administration of study treatment up to end of study

Dalla prima somministrazione fino del trattamento in studio fino alla fine dello studio

E.5.2

Secondary end point(s)

• Mean change in BCVA ETDRS letter score from Baseline, by study visit
• Mean change in CST from Baseline, based on SD-OCT, as assessed by the CRC, by study visit
• Incidence of systemic and ocular AEs and SAEs, from first injection up to the end of the study

• Variazione media del punteggio ETDRS in lettere per la BCVA dal Basale, per visita dello studio.
• Variazione media nel CST dal Basale, basata su SD-OCT, come valutato dal CRC, per visita dello studio.
• Incidenza degli AE e dei SAE sistemici e oculari, dalla prima iniezione fino al termine dello studio.

E.5.2.1

Timepoint(s) of evaluation of this end point

From first administration of study treatment up to end of study

Dalla prima somministrazione fino del trattamento in studio fino alla fine dello studio

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)

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

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

United States

Czechia

France

Germany

Italy

Slovakia

Spain

United Kingdom

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

The end of the study is the date of the last visit of the last subject in the study

La fine dello studio è considerata come la data dell'ultima visita dell'ultimo paziente dello studio

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

122

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)

Patients will return to normal standard of care.

I pazienti torneranno al normale standard di cura.

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

2020-09-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-07-15

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

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