Clinical Trials Register

Summary
EudraCT Number:	2016-000304-29
Sponsor's Protocol Code Number:
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2016-02-15
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

2016-000304-29

A.3

Full title of the trial

Periocular and Intravitreal Corticosteroids for Uveitic Macular Edema (POINT) Trial

A.3.1

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

Investigation into optimal steroid treatment for subjects with sight threatening uveitis

A.3.2

Name or abbreviated title of the trial where available

POINT, v2.0 28th Jun 2016

A.4.1

Sponsor's protocol code number

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02374060

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	MUST Coordinating Centre, John Hopkins Bloomberg School of Public Health
B.1.3.4	Country	United States
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	UCL
B.5.2	Functional name of contact point	Sue Lightman
B.5.3	Address:
B.5.3.1	Street Address	Instutue f Ophthalmology Moorfields Eye Hospital, 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	02075662266
B.5.5	Fax number	02072519350
B.5.6	E-mail	s.lightman@ucl.ac.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	Kenalog
D.2.1.1.2	Name of the Marketing Authorisation holder	E.R. Squibb & Sons Ltd.
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	triamcinolone acetonide
D.3.4	Pharmaceutical form	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	Triamcinolone Acetonide
D.3.9.1	CAS number	76-25-5
D.3.9.4	EV Substance Code	AS1
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	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 Ireland
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Dexamethasone 0.7mg intravitreal implant
D.3.4	Pharmaceutical form	Implant
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.3.9.4	EV Substance Code	AS2
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

Uveitic macular oedema

E.1.1.1

Medical condition in easily understood language

Swelling of part of the retina called the macular, which is responsible for fine vision, occuring due to inflammation in the eye (uveitis)

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	LLT
E.1.2	Classification code	10002709
E.1.2	Term	Anterior uveitis
E.1.2	System Organ Class	100000014995

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10022557
E.1.2	Term	Intermediate uveitis
E.1.2	System Organ Class	100000161411

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10033687
E.1.2	Term	Panuveitis
E.1.2	System Organ Class	100000014975

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10036370
E.1.2	Term	Posterior uveitis
E.1.2	System Organ Class	100000015065

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	10058202
E.1.2	Term	Cystoid 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

To find out which therapy for uveitic macular oedema (swelling of the macula at the back of the eye due to inflammation in the eye) offers the best balance of effectiveness and tolerability, specifically by comparing the relative efficacy and safety of three commonly used treatments for macular oedema: periocular steroid (triamcinolone acetonide); intravitreal steroid (triamcinolone acetonide); and intravitreal slow release steroid implant (dexamethasone implant - Ozurdex®) for the treatment of uveitic macular edema.
The primary outcome measure will be change in macular thickness (i.e. decreased swelling of the macula) at the 8 week visit.

E.2.2

Secondary objectives of the trial

The secondary research questions are to compare the safety and side effect profile of three commonly used treatments for uveitic macular oedema (swelling of the macula at the back of the eye due to inflammation) and to compare change in vision between the three treatments.
The secondary outcome measures will be: pressure in the eye (intraocular pressure), vision (visual acuity), resolution of macular oedema, complications of treatment and cost effectiveness.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patient level inclusion criterion:
1. 18 years of age or older;
Eye level inclusion criteria - at least one eye must meet all of the following conditions
2. Non-infectious anterior, intermediate, posterior or panuveitis; either active or inactive uveitis is acceptable;
3. Macular edema (ME) defined as the presence of central subfield macular thickness
greater than the normal range for the OCT machine being used (>300 μm for Zeiss
Cirrus/Topcon 3DOCT or >320 μm for Heidelberg Spectralis), regardless of the
presence of cysts, as assessed by study ophthalmologist;
4. Best corrected visual acuity (BCVA) 5/200 or better;
5. Baseline intraocular pressure > 5 mm Hg and ≤ 21 mm Hg (current use of 3 or fewer intraocular pressure-lowering medications and/or prior glaucoma surgery are acceptable – note that combination medications, i.e., Cosopt, count as 2 IOP lowering medications);
6. Baseline fluorescein angiogram that is gradable for degree of leakage in the central subfield
7.Pupillary dilation sufficient to allow OCT testing.

E.4

Principal exclusion criteria

Exclusion criteria:
Patient level exclusion criteria:
1. History of infectious endophthalmitis or infectious uveitis in either eye;
2. History of infectious scleritis of any type in either eye. (Note: History of noninfectious scleritis that has been active in past 12 months is an eye-level exclusion –see #11 below.)
3. History of keratitis (with the exception of keratitis due to dry eye)of any type in either eye;
4.History of central serous retinopathy in either eye;
5. For women of childbearing potential: pregnancy, breastfeeding, or a positive pregnancy test; unwilling to practice an adequate birth control method (abstinence, combination barrier and spermicide, or hormonal) for duration of trial;
6. Use of oral acetazolamide or other systemic carbonic anhydrase inhibitor at baseline;
7. Oral prednisone dose > 10 mg per day (or of an alternative corticosteroid at a dose higher than that equipotent to prednisone 10 mg per day) OR oral prednisone dose ≤ 10 mg per day at baseline that has not been stable for at least 4 weeks (note that if patient is off of oral prednisone at baseline (P01 visit), dose stability requirement for past 4 weeks does not apply);
8. Systemic immunosuppressive drug therapy that has not been stable for at least 4 weeks;
9. Known allergy or hypersensitivity to any component of the study drugs;
Eye level exclusion criteria - at least one eye that meets all inclusion criteria cannot have any of the following conditions:
10. History of severe glaucoma as defined by optic nerve damage (cup/disc ratio of ≥ 0.9 or any notching of optic nerve to the rim);
11. Media opacity causing inability to assess fundus or perform OCT;
12. History of active noninfectious scleritis in past 12 months (Note: History of noninfectious scleritis is acceptable if the last episode of active scleritis resolved at least 12 months prior to enrollment);
13. Presence of an epiretinal membrane noted clinically or by OCT that per the judgment of study ophthalmologist may be significant enough to limit improvement of ME (i.e., causing substantial wrinkling of the retinal surface)81;
14. Torn or ruptured posterior lens capsule
15. Presence of silicone oil;
16. Periocular or intravitreal corticosteroid injection in past 8 weeks;
17. Injection of dexamethasone intravitreal implant in past 12 weeks;
18. Placement of fluocinolone acetonide implant (Retisert) in past 3 years;

E.5 End points

E.5.1

Primary end point(s)

Percent change in central subfield macular thickness from the baseline OCT measurement at the 8-week visit.

E.5.1.1

Timepoint(s) of evaluation of this end point

8 week visit

E.5.2

Secondary end point(s)

• Rate of IOP elevation of >21 mm Hg or ≥ 10 mm Hg from baseline during the 24 weeks of follow-up
• Percent change in macular thickness as measured by OCT over the 24 weeks of follow-up
• Proportion of eyes with macular edema events over the 24 weeks of follow-up
- ≥20% reduction in macular thickness (or normalization of macular thickness even if there is <20% reduction)
- ”Resolution”, defined as normalization of the macular thickness to within +2 standard deviations of the normative mean for the OCT machine used
- Worsening defined as a 20% increase in macular thickness from the lowest value after an injection
- “Recurrence” defined as >20% increase in the central subfield measurement on OCT to an abnormal value in an eye that previously had resolution of ME
• Mean change in BCVA over the 24 weeks of follow-up.
Best-corrected visual acuity score will be measured at every study visit under standardized lighting conditions by certified study examiners masked to study treatment using logarithmic (ETDRS) visual acuity charts.
• Inflammation as graded using the semi quantitative scales used in the MUST Trial i.e., clinician grading of the presence and extent of anterior chamber cells, anterior vitreous cells, and vitreous haze based on previously published standard ordinal scales (0, trace, 1+, 2+, 3+, 4+) using the scales endorsed by the Standardization of Uveitis Nomenclature Working Group when applicable
• Safety outcomes including elevated IOP ( >30 mm Hg thresholds ); new onset posterior subcapsular (PSC) cataract or progression of pre-existing PSC (using the Age-Related Eye Disease Study [AREDS] scheme; vitreous hemorrhage; retinal tear/detachment; endophthalmitis; severe vision loss (≥15 Early Treatment Diabetic Retinopathy Study [ETDRS] letters) during the 24 weeks of follow-up.
• Cost-effectiveness of treatments for uveitic macular edema during the 24 weeks of follow-up will be assessed by enumerating costs of treatments and procedures for uveitis during the 24 week follow-up; participants’ utilities will be measure with the EuroQol questionnaire.
• Visual function related quality of life as measured by the NEI Visual Function Questionnaire (25 item version).

E.5.2.1

Timepoint(s) of evaluation of this end point

Evaluated at week 4, 8, 12, 16, 20 and 24

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

Yes

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

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)

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

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

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

Australia

United Kingdom

United States

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 across all the sites

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