Clinical Trials Register

Summary
EudraCT Number:	2010-022616-39
Sponsor's Protocol Code Number:	CRFB002DGB14
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:	2010-10-27
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

2010-022616-39

A.3

Full title of the trial

RELIGHT - Ranibizumab treatment of diabetic macular oEdema with bimonthLy monItorinG after a pHase of initial Treatment. A UK, 18-month, prospective, open-label, multicenter, single-arm Phase IIIb study, with 12-month primary endpoint, assessing the efficacy and safety of Lucentis (Ranibizumab) in patients with visual impairment due to diabetic macular oedema.

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

RELIGHT

A.4.1

Sponsor's protocol code number

CRFB002DGB14

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	Novartis Pharmaceuticals UK Ltd
B.1.3.4	Country	United Kingdom
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	Novartis Pharmaceuticals UK 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	Novartis Pharmaceuticals UK Ltd
B.5.2	Functional name of contact point	Medical Collaboration Centre
B.5.3	Address:
B.5.3.1	Street Address	Frimley Business Park
B.5.3.2	Town/ city	Frimley
B.5.3.3	Post code	GU16 7SR
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+441276698370
B.5.5	Fax number	+441276698449
B.5.6	E-mail	medinfo.uk@novartis.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	Yes
D.2.1.1.1	Trade name	Lucentis
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Ltd
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	Ranibizumab
D.3.2	Product code	RFB002
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.3.11 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

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.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

•To evaluate the efficacy of 0.5 mg Lucentis (ranibizumab), as measured by the mean change from baseline in Best Corrected Visual Acuity (BCVA) at 12 months,

E.2.2

Secondary objectives of the trial

-to evaluate the efficacy of 0.5 mg Lucentis (ranibizumab), as measured by the mean change from baseline in Best Corrected Visual Acuity (BCVA) at 18 months,
-to evaluate the safety of 0.5 mg Lucentis (ranibizumab), as measured by ocular and systemic adverse events at 18 months,
- to evaluate the time course of BCVA changes with 0.5 mg Lucentis (ranibizumab) from 6 months to 12 and 18 months,
- to evaluate the time course of changes in central retinal thickness with 0.5 mg Lucentis (ranibizumab) from baseline to 12 and 18 months,
- to evaluate the time course of changes in central retinal thickness with 0.5 mg Lucentis (ranibizumab) from 6 months to 12 and 18 months,
- to evaluate the time course of changes in severity of diabetic retinopathy with 0.5 mg Lucentis (ranibizumab) from baseline to 12 and 18 months,

-see protocol for remaining secondary objectives-

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Diabetic Retinopathy Sub-study Exploratory objective(s)

 -to assess the level of association between diabetic retinopathy at study entry and anatomical response (as measured by central retinal thickness reduction) to ranibizumab,
 -to assess if baseline diabetic retinopathy severity correlates with baseline DMO severity,
 -to assess the relative change in diabetic retinopathy from baseline to Month 12 with ranibizumab, using ETDRS severity scores.
 -to assess if mean injection frequencies differ by baseline diabetic retinopathy severity.

E.3

Principal inclusion criteria

1) Male or female patients ≥ 18 years of age who have given written informed consent.
2) Patients with Type 1 or Type 2 diabetes mellitus.
3) Patients with visual impairment due to focal or diffuse DMO, and not other causes, in at least one eye who are eligible for laser treatment in the opinion of the investigator. If both eyes are eligible, the one with the worse visual acuity, as assessed at Visit 1, will be selected for study treatment unless, based on medical reasons, the investigator deems the other eye the more appropriate candidate for study treatment.
4) BCVA between 78 and 24 in the study eye using ETDRS-like visual acuity testing charts after adjustment for the testing distance of 4 metres (approximate Snellen equivalent of 6/9 to 6/96) at screening.
5) Increased central retinal thickness which, in the opinion of the investigator, is due to DMO.

E.4

Principal exclusion criteria

1) Previous participation in any clinical studies of investigational drugs (excluding vitamins and minerals) within 1 month (or a period corresponding to 5 half-lives of the investigational drug, whatever is longer) prior to first study drug treatment.
2) Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they are using two birth control methods. The two methods can be a double barrier method or a barrier method plus a hormonal method. Adequate barrier methods of contraception include: diaphragm, condom (by the partner), intrauterine device (copper or hormonal), sponge or spermicide. Hormonal contraceptives include any marketed contraceptive agent that includes an oestrogen and/or a progestational agent.
3) Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive serum pregnancy test (hCG >5 mIU/mL).
4) Inability to comply with study procedures.
5) Concomitant conditions in the study eye which could, in the opinion of the investigator, prevent the improvement of visual acuity on study treatment (e.g cataract, retinal vascular occlusion, retinal detachment, macular hole, vitreomacular traction, or choroidal neovascularization of any cause e.g. AMD, ocular histoplasmosis, or pathologic myopia).
6) Active intraocular inflammation (grade trace or above) or infection (e.g. conjunctivitis, keratitis, scleritis, endophthalmitis) in either eye at enrollment .
7) History of uveitis in either eye at any time.
8) Structural damage within 0.5 disc diameter of the center of the macular in the study eye likely to preclude improvement in visual acuity following the resolution of macular oedema, including atrophy of the retinal pigment epithelium, subretinal fibrosis, laser scar(s), epiretinal membrane involving fovea or organized hard exudate plaques.
9) Planned medical or surgical intervention during the 18-month study period.
10) Uncontrolled glaucoma in either eye at screening (IOP > 24 mmHg on medication or according to investigator’s judgment).
11) Neovascularization of the iris in either eye.
12) Active proliferative diabetic retinopathy in the study eye.
13) Panretinal or focal/grid laser photocoagulation in the study eye within 3 months prior to Visit 2.
14) Treatment with anti-angiogenic drugs and corticosteroids in the study eye (pegaptanib sodium, anecortave acetate, bevacizumab, ranibizumab, VEGF-Trap, etc.) within 3 months prior to Visit 2 .
15) Any intraocular surgery in the study eye within 3 months prior to Visit 2.
16) History of vitrectomy in study eye.
17) Ocular conditions in the study eye that require chronic concomitant therapy with topical ocular or systemically administered corticosteroids.
18) History of acute thromboembolic event within 4 months of screening.
19) Renal failure requiring dialysis or renal transplant OR renal insufficiency with e-GFR < 30 levels at screening.
20) Untreated diabetes mellitus.
21) Blood pressure systolic > 160 mmHg or diastolic > 100 mmHg at screening and Visit 2.
22) Current use of, or likely need, for systemic medications known to be toxic to the lens, retina or optic nerve, including Deferoxamine, Chloroquine/ hydroxychloroquine (Plaquenil), Tamoxifen, Phenothiazines and Ethambutol.
23) Current use of, or likely need for, glitazones.
24) Known hypersensitivity to ranibizumab or any component thereof or drugs of similar chemical classes.
25) Any type of advanced, severe or unstable disease or its treatment, that may interfere with primary and/or secondary variable evaluations including any medical condition that could be expected to progress, recur, or change to such an extend that it may bias the assessment of the clinical status of the patient to a significant degree or put the patient at special risk.

E.5 End points

E.5.1

Primary end point(s)

Mean change from baseline in Best Corrected Visual Acuity (BCVA) at 12 months.

E.5.1.1

Timepoint(s) of evaluation of this end point

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

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

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

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	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	150
F.4.2	For a multinational trial
F.4.2.2	In the whole clinical trial	150

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

2010-11-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-11-30

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-04-15

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