Clinical Trials Register

Summary
EudraCT Number:	2012-003661-17
Sponsor's Protocol Code Number:	SS01
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-09-24
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

UK - MHRA

A.2

EudraCT number

2012-003661-17

A.3

Full title of the trial

A Multicentre Prospective Open-label Randomised Clinical Trial Comparing the Efficacy of Fixed versus PRN dosing of 700 µg Dexamethasone Posterior Segment Drug Delivery System (DEX PS DDS) in patients with refractory diabetic macular oedema.

A.3.1

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

A Multicentre Prospective Open-label Randomised Clinical Trial Comparing the Efficacy of Fixed versus Variable dosing of 700 µg Dexamethasone Posterior Segment Drug Delivery System (DEX PS DDS) in patients with refractory diabetic macular oedema.

A.3.2

Name or abbreviated title of the trial where available

OZDRY

A.4.1

Sponsor's protocol code number

SS01

A.5.4

Other Identifiers

Name:

R&D reference

Number:

SIVS1002

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	Moorfields Eye Hospital NHS Foundation Trust
B.1.3.4	Country	United Kingdom
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	Allergan Pharmaceuticals Ltd
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	Moorfields Eye Hospital
B.5.2	Functional name of contact point	Natasha Ajraam
B.5.3	Address:
B.5.3.1	Street Address	162, City Road
B.5.3.2	Town/ city	London
B.5.3.3	Post code	EC1V 2PD
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	020 7253 3411 x2937
B.5.5	Fax number	02075662315
B.5.6	E-mail	natasha.ajraam@moorfields.nhs.uk

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	OZURDEX
D.2.1.1.2	Name of the Marketing Authorisation holder	Allergan Pharmaceuticals 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.3.1	Product name	OZURDEX
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	Dexamethasone
D.3.9.1	CAS number	50-02-2
D.3.9.3	Other descriptive name	Ozurdex
D.3.9.4	EV Substance Code	AS1
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	700
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes

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

E.1.1.1

Medical condition in easily understood language

diabetes related swelling of the central retina

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10057915
E.1.2	Term	Diabetic macular oedema
E.1.2	System Organ Class	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

Is OCT-guided PRN dosing of 700 µg Dexamethasone Posterior Segment Drug Delivery System (DEX PS DDS)in patients with refractory DMO non-inferior to 5 monthly fixed dosing of this drug in terms of visual acuity outcomes?

E.2.2

Secondary objectives of the trial

1. To evaluate the effects of PRN dosing relative to fixed dosing of 700 µg Dexamethasone Posterior Segment Drug Delivery System (DEX PS DDS) on patient reported outcomes in patients with refractory DMO
2. To evaluate the safety of PRN dosing relative to fixed dosing of 700 µg Dexamethasone Posterior Segment Drug Delivery System (DEX PS DDS) in patients with refractory DMO.
3. To evaluate the effects of PRN dosing relative to fixed dosing of 700 µg Dexamethasone Posterior Segment Drug Delivery System (DEX PS DDS) on anatomical changes in patients with refractory DMO

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subjects of either sex aged 18 years or over
2. Diagnosis of diabetes mellitus (type 1 or type 2). Any one of the following will be considere to be sufficient evidence that diabetes is present:
i. Current regular use of insulin for the treatment of diabetes
ii. Current regular use of oral anti-hyperglycaemic agents for the treatment of diabetes
iii. Documented diabetes by ADA and/or WHO criteria (see Procedures Manual for Diagnosis of Diabetes)
3. Best corrected visual acuity in the study eye between ≥34 and ≤73 ETDRS letters at 1m at baseline attributable to DMO.
4. On clinical exam at baseline in the study eye, retinal thickening due to diabetic macular oedema involving the centre of the macula and OCT central subfield > 300 microns (Spectralis) despite previous therapy.
5. Media clarity, pupillary dilation, and subject cooperation sufficient for adequate fundus photographs.
6. Ability to return for study visits
7. Visual acuity in fellow eye ≥ 2/60
8. Ability to give informed consent throughout the duration of the study

E.4

Principal exclusion criteria

The following exclusions apply to the study eye only (i.e. they may be present for the non study eye, provided that inclusion criterion 8 is met):
1.Macular ischaemia (FAZ > 1000µm in diameter or severe perifoveal intercapillary loss on IVFA).
2.Macular oedema is considered to be due to a cause other than diabetic macular oedema. An eye should not be considered eligible if: (1) the macular oedema is considered to be related to cataract extraction or (2) clinical exam and/or OCT suggest that vitreoretinal interface abnormalities disease (e.g., a taut posterior hyaloid or epiretinal embrane) is the primary cause of the macular oedema.
3.Co-existent ocular disease: An ocular condition is present such that, in the opinion of the investigator, visual acuity would not improve from resolution of macular oedema (e.g., foveal atrophy, pigmentary changes, dense subfoveal hard exudates, non retinal conditions, such as amblyopia).
4.An ocular condition is present (other than diabetes) that, in the opinion of the investigator, might affect macular oedema or alter visual acuity during the course of the study (e.g. vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, Irvine-Gass syndrome, etc).
5.A substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more (i.e., cataract would be reducing acuity to 6/12 or worse if eye was otherwise normal).
6.History of treatment for DMO with peribulbar or intravitreal steroids in the study eye in the past 6 months.
7. History of macular laser in study eye in the last 3 months.
8. History of antiVEGF therapy within the last 1 month.
9. Active proliferative diabetic retinopathy or rubeosis in the study eye at baseline. (Stable and treated proliferative diabetic retinopathy may be included).
10. A condition that, in the opinion of the investigator, would preclude participation in the study.
11. A past medical history of significant renal disease, defined as a history of chronic renal failure requiring dialysis or kidney transplant
12.. Major surgery within 28 days prior to randomisation or major surgery planned during the next 12 months at baseline. Major surgery is defined as a surgical procedure that is more extensive than fine needle biopsy/aspiration, placement of a central venous access device, removal/biopsy of a skin lesion, or placement of a peripheral venous catheter.
13. Participation in an investigational trial within 30 days of randomisation that involved treatment with any drug that has not received regulatory approval at the time of study entry. Note: subjects cannot receive another investigational drug while participating in the study.
14. Pregnant or lactating women or women intending to become pregnant within the study period.
15. History of major ocular surgery (including cataract extraction, scleral buckle, any intraocular surgery, etc.) within prior 3 months or anticipated within the next 6 months following randomisation.
16. Aphakia
17. A diagnosis of glaucoma which in the opinion of a glaucoma specialist is at high risk of progression or ocular hypertension requiring at least one topical medication.
19. History of vitrectomy in study eye.
20. Exam evidence of external ocular infection, including conjunctivitis, chalazion, or severe blepharitis. If treated these subjects can be included.
21. Known allergy to fluorescein dye or to any component of the study drug.
22. Fertile male unwilling to use contraception for the duration of the study
Contraceptive advice to women of child-bearing age and fertile males
Women of child-bearing potential will be advised to use contraception for the duration of the study. They will be advised not to deliberately become pregnant during the trial and use contraception for 3 months after the study concludes. Women who become pregnant during the trial will have the study drug immediately discontinued and will be withdrawn from the trial. Fertile males will be advised to use contraception for the duration of the trial.

E.5 End points

E.5.1

Primary end point(s)

Primary outcome is the difference between arms in the change from baseline in best corrected visual acuity at 12 months.

E.5.1.1

Timepoint(s) of evaluation of this end point

12 months

E.5.2

Secondary end point(s)

1. Difference between arms in proportion of patients with improvement of BCVA (gain of 10 ETDRS letters or more)
2. Difference between arms in proportion of patients with stabilization of BCVA (loss of less than 15 ETDRS letters)
3. Difference between arms in change from baseline in central retinal thickness as measured by OCT
4. Difference between arms in change from baseline in each domain and composite scores of the National Eye Institute Visual function questionnaire (VFQ-25), RetTSQ and RetDQoL.
5. Difference between arms in changes in morphological characteristics of diabetic macular oedema on OCT.
6. Difference between arms in proportion of patients with decrease in leakage on FFA, foveal avascular zone parameters and ETDRS grade of retinopathy at month 12.
7. Difference between arms in number of treatments.
8. Difference between arms in changes in distribution of BCVA change from baseline in 5 categories: a) ≥15 letters improvement b) ≥ 5 letters and < 15 letter improvement c) no change (i.e. ≥ -4 and ≤4 letters d) ≥5 letters and <15 letters worsening and e) ≥15 letters worsening.
9. Difference between arms in adverse events.
Further exploratory analyses may be done as new data emerges.

E.5.2.1

Timepoint(s) of evaluation of this end point

12 months

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

Yes

E.8.1.3

Single blind

Yes

E.8.1.4

Double blind

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

Ozurdex 5 monthly dosing

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

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

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

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