Clinical Trials Register

Summary
EudraCT Number:	2020-000362-42
Sponsor's Protocol Code Number:	THR-687-002
National Competent Authority:	Slovakia - SIDC (Slovak)
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2021-06-29
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

Slovakia - SIDC (Slovak)

A.2

EudraCT number

2020-000362-42

A.3

Full title of the trial

A Phase 2, randomised, multicentre study to assess the dose level of multiple THR-687 injections and to evaluate the efficacy and safety of THR-687 versus aflibercept for the treatment of diabetic macular oedema (DME)

Randomizované, multicentrické klinické skúšanie fázy 2 na vyhodnotenie úrovne dávky pri viacnásobných injekciách THR-687 a na vyhodnotenie účinnosti a bezpečnosti THR-687 v porovnaní s afliberceptom pri liečbe diabetického makulárneho edému (DME)

A.3.1

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

A study to evaluate THR-687 treatment for diabetic macular oedema

Štúdia hodnotiaca liečbu diabetického makulárneho edému s THR-687

A.3.2

Name or abbreviated title of the trial where available

INTEGRAL

A.4.1

Sponsor's protocol code number

THR-687-002

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	3001
B.5.3.4	Country	Belgium
B.5.4	Telephone number	+3216751 310
B.5.5	Fax number	+3216751 311
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-687
D.3.2	Product code	THR-687
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	NA
D.3.9.2	Current sponsor code	THR-687
D.3.9.3	Other descriptive name	THR-687
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	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	Eylea 40 mg/mL solution for injection in pre-filled syringe
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	Eylea
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	Aflibercept
D.3.9.1	CAS number	862111-32-8
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	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 oedema (DME)

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.

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

Part A
- to select the THR-687 dose level (1.2mg or 2.0mg) to be further assessed in Part B. Dose level selection will be based on a benefit risk assessment conducted when all subjects completed the Month 3 visit.

Part B
- to assess the difference in treatment effect between THR 687 and aflibercept, in terms of the change from Baseline in best corrected visual acuity (BCVA) at Month 3, in Rx naïve subjects.

E.2.2

Secondary objectives of the trial

- To assess the efficacy of multiple IVT injections of THR-687 over-time.
- To assess the safety of multiple IVT injections of THR-687 over-time.

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 ≤ 78 (Part A) or ≤ 73 (Part B) and ≥ 39 (both study parts) in the study eye
- CI-DME with CST ≥ 300µm in men, or ≥ 285µm in women, measured from the retinal pigment epithelium (RPE) to the internal limiting membrane (ILM) inclusively, on SD-OCT, in the study eye
- BCVA ETDRS letter score ≥ 34 in the fellow eye

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 IMPs
- ETDRS severity level ≥ 61 (Part A), or ETDRS severity level ≥65 (Part B), on colour fundus photograph, in the study eye
- Presence of iris neovascularisation in the study eye
- Previous confounding medications / interventions, or their planned administration during the study
- Uncontrolled glaucoma in the study eye
- Previously received THR-687 or any other experimental therapy for DME, in either eye
- Any active or suspected ocular or periocular infection, or active intraocular inflammation, in either eye
- Untreated diabetes
- Glycated haemoglobin A (HbA1c) > 12%
- Uncontrolled hypertension

E.5 End points

E.5.1

Primary end point(s)

Change from Baseline in BCVA ETDRS letter score

E.5.1.1

Timepoint(s) of evaluation of this end point

At month 3

E.5.2

Secondary end point(s)

- Weighted average of the change from Baseline in BCVA ETDRS letter score from Day 8 through Month 3 using the trapezoidal rule (AUC)
- Change from Baseline in BCVA ETDRS letter score, by study visit
- Change from Baseline in CST, based on SD-OCT, as assessed by the CRC, by study visit
- Incidence of ocular and non-ocular AEs and SAEs, from first injection up to the end of the study

E.5.2.1

Timepoint(s) of evaluation of this end point

From first administration of study treatment up to end of study

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)

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

India

Israel

United States

Czechia

Estonia

Germany

Hungary

Italy

Latvia

Lithuania

Poland

Portugal

Slovakia

Spain

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

LVLS

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

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:

151

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

152

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

186

F.4.2.2

In the whole clinical trial

303

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)

Patient will return to normal 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

2021-10-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-07-14

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

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