Clinical Trials Register

Summary
EudraCT Number:	2014-003491-23
Sponsor's Protocol Code Number:	4C-2014-06
National Competent Authority:	Portugal - INFARMED
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-10-14
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

Portugal - INFARMED

A.2

EudraCT number

2014-003491-23

A.3

Full title of the trial

A non-randomised, open-label, multicenter phase 4 pilot study on the effect and safety of Iluvien® in chronic diabetic macular edema patients considered insufficiently responsive to available therapies with or without intravitreal corticosteroid therapy. (RESPOND)

A.3.1

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

This is a non-randomised, open-label which means that patients know they will receive the active medicine. No placebo will be used. The study will examine the effect and safety of Iluvien® in chronic diabetic macular edema patients. Patients would have been treated previously with other available therapies such as laser photo coagulation or a therapy called anti-VEGF or with corticosteroid therapy.

A.3.2

Name or abbreviated title of the trial where available

RESPOND

A.4.1

Sponsor's protocol code number

4C-2014-06

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	AIBILI – Association for Innovation and Biomedical Research on Light and Image
B.1.3.4	Country	Portugal
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Alimera Sciences Limited
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AIBILI – Association for Innovation and Biomedical Research on Light and Image
B.5.2	Functional name of contact point	Tiago Ferreira
B.5.3	Address:
B.5.3.1	Street Address	Azinhaga de Santa Comba, Celas
B.5.3.2	Town/ city	Coimbra
B.5.3.3	Post code	3000-548
B.5.3.4	Country	Portugal
B.5.4	Telephone number	00351239480141
B.5.5	Fax number	00351239480117
B.5.6	E-mail	tferreira@aibili.pt

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	Yes
D.2.1.1.1	Trade name	ILUVIEN 190 microgramas implante intravítreo em apliacador.
D.2.1.1.2	Name of the Marketing Authorisation holder	Alimera Sciences Limited
D.2.1.2	Country which granted the Marketing Authorisation	Portugal
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	Intravitreal implant in applicator
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	FLUOCINOLONE ACETONIDE
D.3.9.1	CAS number	67-73-2
D.3.9.4	EV Substance Code	SUB07714MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	190
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Chronic Diabetic Medical Edema

E.1.1.1

Medical condition in easily understood language

Diabetic Macular Edema is a complication of diabetes caused by fluid accumulation in the central portion of the eye called the macula.

E.1.1.2

Therapeutic area

Diseases [C] - Eye Diseases [C11]

MedDRA Classification

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 assess the effect and safety of ILUVIEN in patients with chronic DME insufficiently responsive to prior available therapies with or without prior history of intraocular corticosteroid therapy.

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients ≥18 years of age, of either sex that have signed informed consent.
2. Chronic DME, defined as a history of macular edema with duration > 1 year having already received other therapy, based on investigator’s clinical evaluation and demonstrated using fundoscopic photography and SD-OCT.
3. Patients considered as insufficiently responsive as defined as having underwent other previous treatments, including at least 3 anti-VEGF injections in the last 6 months, and the following:
• Mean central foveal thickness (central subfield thickness) ≥ 290um in women and ≥ 305um in men in Zeiss Cirrus OR ≥ 305um in women and ≥ 320um in men in Heidelberg Spectralis, in the study eye as measured using SD-OCT;
• Vision impairment (20/50 to 20/400 using Snellen visual acuity equivalent) related to DME;
• If in the Investigator’s opinion a further improvement is possible.

E.4

Principal exclusion criteria

1. IOP > 21 mmHg at screening (day -14) in the study eye.
2. Historical rise in IOP > 25 mmHg following treatment with an intravitreal corticosteroid in the study eye.
3. Use of ≥ 2 active agents as IOP-lowering medications to control IOP at screening in the study eye.
4. Patients that have vitreomacular traction in DME and opaque media in the study eye.
5. Patients with severe proliferative diabetic retinopathy requiring pan retinal photocoagulation in the study eye.
6. Pregnant or breastfeeding women.
7. Patients diagnosed with active angiographic central macular ischaemia prior to screening in the study eye.
8. Patients that have received pan retinal photocoagulation or undergone cataract surgery in the 3 months prior to the screening visit in the study eye.
9. Patients with contraindications:
a. Presence of pre-existing glaucoma.
b. Active or suspected ocular or periocular infection.
c. The patient is hypersensitive to the active agent or to one of the excipients.
10. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant UNLESS they are: using a highly effective method of birth control (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, and some intrauterine devices – IUDs). Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) are not acceptable. Reliable contraception should be maintained throughout the study and for 30 days after study drug discontinuation.

E.5 End points

E.5.1

Primary end point(s)

- Changes in best-corrected visual acuity (BCVA) from baseline to Month-12;
- Changes in central retinal thickness assessed using spectral domain optical coherence tomography (SD-OCT) from baseline to Month-12;
- Occurrence of Adverse events, namely cataract and elevated IOP

E.5.1.1

Timepoint(s) of evaluation of this end point

Evaluation done at Months 1, 3, 6, 9 and 12.

E.5.2

Secondary end point(s)

Not applicable

E.5.2.1

Timepoint(s) of evaluation of this end point

Not applicable

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)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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

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.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)

None

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

2014-10-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-10-10

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-03-09

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