Clinical Trials Register

Summary
EudraCT Number:	2015-001940-12
Sponsor's Protocol Code Number:	14166NL-AS
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:	2015-09-09
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

2015-001940-12

A.3

Full title of the trial

A phase II Clinical Trial on the use of ARA 290 for the treatment of diabetic macular oedema (ARA 290-DMO)

A.3.1

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

A phase II Clinical Trial on the use of ARA 290 for the treatment of diabetic macular oedema

A.3.2

Name or abbreviated title of the trial where available

The use of ARA 290 for the treatment of DMO (ARA 290-DMO) v1

A.4.1

Sponsor's protocol code number

14166NL-AS

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN16962255

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	Belfast Health & Social Care 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	Araim Pharmaceuticals, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Northern Ireland Clinical Trials Unit (NICTU)
B.5.2	Functional name of contact point	NICTU
B.5.3	Address:
B.5.3.1	Street Address	1st Floor, Elliott Dynes Center, Royal Hospitals, Grosvenor Road
B.5.3.2	Town/ city	Belfast
B.5.3.3	Post code	BT12 6BA
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	02890635794
B.5.5	Fax number	02890633328
B.5.6	E-mail	info@nictu.hscni.net

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.2.1.1.1	Trade name	ARA290
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	ARA 290
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ARA 290
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5.6
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

Diabetic macular oedema

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	18.0
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.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The aim or primary objective of the study is to determine whether ARA 290 administered at a daily dose of 4mg subcutaneously for 12 weeks to patients with diabetes mellitus (DM) and DMO will have a beneficial effect on mean change in best corrected visual acuity (BCVA) from baseline values to week 12.

E.2.2

Secondary objectives of the trial

The secondary objectives are to determine whether ARA 290 administered at a daily dose of 4mg subcutaneously for 12 weeks to patients with DM and DMO can improve vision (as determined by the % of participants with a ≥ 10 and ≥ 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letter gain), reduce central subfield thickness, increase central retinal sensitivity, increase tear production and improve retinal perfusion and quality of life with no deleterious side effects. The effects of ARA 290 on the systemic and metabolic control of participants will be also evaluated in an exploratory manner.
ARA 290 antibodies will be determined as, if they were to develop in people undergoing this treatment they could have an impact on the potential subsequent response to it.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients with diabetic retinopathy and centre involving DMO with a central subfield thickness of > or equal to 400 microns, as determined using SD-OCT;
2. >= 18 years of age
3. Clear media and naïve to previous treatments for DMO.

E.4

Principal exclusion criteria

1. Macular oedema related to other retinal disease
2. Hazy media that prevents adequate retinal imaging
3. Allergy to fluorescein
4. Previous treatments for DMO
5. DMO with central subfield thickness of < 400 microns
6. Patients on systemic or topical steroids
7. Use of erythropoiesis stimulating agents within the two months prior to screening or during the trial
8. Treated with any other investigational medication or device within 60 days
9. Pregnant women, women who have not yet reached the menopause (no menses for ≥ 12 months without an alternative medical cause) who test positive for pregnancy, are unwilling to take a pregnancy test prior to trial entry or are unwilling to undertake adequate precautions to prevent pregnancy for the duration of the trial.
10. Female patients who are breastfeeding
11. Active proliferative diabetic retinopathy (PDR) requiring treatment.
12. Patients with other eye diseases besides diabetic retinopathy
13. Patients who are unable or unwilling to commit to the study schedule of events
14. Serious illness that is likely to affect the patient's ability to complete the study

Any patient showing improvement between the initial screening and presenting for the first screening/baseline visit will no longer be eligible for the study, will be recorded as a screen failure and will not be entered on to the study.

E.5 End points

E.5.1

Primary end point(s)

Change from baseline to week 12 (+/– 7 days) in best corrected distance visual acuity

E.5.1.1

Timepoint(s) of evaluation of this end point

Best corrected distance visual acuity will be obtained in both eyes by a trained optometrist using the Early Treatment Diabetic Retinopathy Study (ETDRS) charts at baseline and at weeks 4, 8 and 12. If at week 12 the retina is dry, a further visit at week 16 will be undertaken and BCVA will be obtained at this visit. The EDTRS total score will be recorded and used for the analysis.

E.5.2

Secondary end point(s)

Changes from baseline to week 12 (+/– 7 days) in:

1. Central subfield thickness
2. Central retinal sensitivity
3. Retinal perfusion
4. Tear production
5. Patient reported outcomes
6. ARA 290 antibodies
7. Adverse events

% of participants with ≥ 10 ETDRS letter gain
% of participants with ≥ 15 ETDRS letter gain

E.5.2.1

Timepoint(s) of evaluation of this end point

Central subfield thickness: baseline, weeks 4, 8 and 12 (and week 16 if the retina is dry at week 12)
Central retinal sensitivity: baseline and week 12 (and week 16 if the retina is dry at week 12)
Retinal perfusion: baseline and week 12
Tear production: baseline and week 12 (and week 16 if the retina is dry at week 12)
Visual acuity; % of participants with ≥ 10 and ≥ 15 ETDRS letter gain: week 12 (and week 16 if the retina is dry at week 12)
Patient reported outcomes: EQ-5D-5L and NEI-VFQ_25 at baseline and week 12 (and week 16 if applicable). C-SSRS at baseline and weeks 4, 8 and 12 (and week 16 if applicable)
Inflammatory markers: baseline and week 12.
ARA 290 antibodies: baseline and week 12
AEs: Tel: 2 weeks after first & 4 weeks after last visit. Each 4 week clinic visit.

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

ARA290 has been used in previous phase 1 clinical trials; the current one explores a different use.

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

E.8.1.1

Randomised

E.8.1.2

Open

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.8.2.4

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.8.5

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. For the purposes of submitting the end of trial notification to the Sponsor, MHRA and REC, the end of trial will be considered to be when the database lock occurs for the final analysis.

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