A randomized, double-masked, multicenter, laser-controlled Phase III study assessing the efficacy and safety of ranibizumab (intravitreal injections) as adjunctive and mono-therapy in patients with visual impairment due to diabetic macular edema - RESTORE

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-004877-24-HU
• Date of registration: 19/05/2008
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A randomized, double-masked, multicenter, laser-controlled Phase III study assessing the efficacy and safety of ranibizumab (intravitreal injections) as adjunctive and mono-therapy in patients with visual impairment due to diabetic macular edema - RESTORE
• Scientific title: A randomized, double-masked, multicenter, laser-controlled Phase III study assessing the efficacy and safety of ranibizumab (intravitreal injections) as adjunctive and mono-therapy in patients with visual impairment due to diabetic macular edema - RESTORE
• Date of first enrolment: 09/07/2008
• Target sample size: 315
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-004877-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Laser photocoagulation

Countries of recruitment

Belgium, France, Germany, Greece, Hungary, Italy, Netherlands, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female patients >18 years of age who have signed an informed consent
2. Patients with Type 1 or Type 2 diabetes mellitus (according to ADA or WHO Guidelines) with HbA1c not more than 10.0% at screening (Visit 1). Patients should be on diet, exercise, and/or pharmacological treatment for diabetes.
3. Patients with visual impairment due to focal or diffuse DME in at least one eye who are eligible for laser treatment in the opinion of the investigator. If both eyes are eligible, the eye 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 to receive study treatment. The study eye must fulfill the following criteria at
Visit 1:
• BCVA score between 78 and 39 letters, inclusively, using ETDRS-like visual acuity
testing charts at a testing distance of 4 meters (approximate Snellen equivalent of
20/32 to 20/160)
• Decrease in vision is due to DME and not due to other causes, in the opinion of the
investigator
4. Medication for the management of diabetes must have been stable within 3 months prior to randomization and is expected to remain stable during the course of the study.
Are the trial subjects under 18? no
Number of subjects for this age range:
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

Exclusion criteria:
Ocular concomitant conditions/ diseases
1. Concomitant conditions in the study eye which could, in the opinion of the investigator, prevent the improvement of visual acuity on study treatment
2. Active intraocular inflammation (grade trace or above) in either eye
3. Any active infection (e.g. conjunctivitis, keratitis, scleritis, uveitis, endophthalmitis) in either eye
4. History of uveitis in either eye
5. Structural damage within 0.5 disc diameter of the center of the macula in the study eye likely to preclude improvement in visual acuity following the resolution of macular edema, including atrophy of the retinal pigment epithelium, subretinal fibrosis, laser scar(s), epiretinal membrane involving fovea or organized hard exudate plaques
6. Ocular disorders in the study eye that may confound interpretation of study results, compromise visual acuity or require medical or surgical intervention during the 12-month study period, including cataract, retinal vascular occlusion, retinal detachment, macular hole, or choroidal neovascularization of any cause (e.g., AMD, ocular histoplasmosis, or pathologic myopia)
7. Uncontrolled glaucoma in either eye (e.g. IOP > 24 mmHg on medications, or according to investigator’s judgement)
8. Neovascularization of the iris in either eye
9. Evidence of vitreomacular traction in either eye
10. Active proliferative diabetic retinopathy in the study eye
11. Patients who are monocular or have a BCVA score in the non-study eye (fellow eye) = 24 letters (approximate Snellen equivalent of 20/320) at Visit 1

Ocular treatments
12. Panretinal laser photocoagulation in the study eye within 6 months prior to or during the study
13. Focal/grid laser photocoagulation in the study eye within 3 months prior to study entry
14. Treatment with anti-angiogenic drugs (pegaptanib sodium, anecortave acetate,
bevacizumab, ranibizumab, etc.) in study eye within 3 months prior to randomization
15. Any intraocular surgery in the study eye within 3 months prior to randomization
16. History of vitrectomy in study eye
17. History of intravitreal corticosteroid treatment in phakic study eye
18. Intravitreal corticosteroids in post-cataract surgical study eyes (aphakic or pseudophakic without damaged posterior capsule) within 3 months prior to randomization
19. Ocular conditions in the study eye that require chronic concomitant therapy with topical ocular or systemically administered corticosteroids

Systemic conditions or treatments
20. History of stroke
21. Renal failure requiring dialysis or renal transplant OR renal insufficiency with creatinine levels > 2.0 mg/dl
22. Untreated diabetes mellitus
23. Blood pressure systolic > 160 mmHg or diastolic > 100 mmHg
24. Untreated hypertension or change in antihypertensive treatment within 3 months
preceding Baseline
25. 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
26. Known hypersensitivity to ranibizumab or any component of the ranibizumab formulation or fluorescein
27. Any type of advanced, severe or unstable disease or it`s treatment, that could interfere with primary and/or secondary outcome 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

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Diabetic Macular Edema (DME)
MedDRA version: 9.1 Level: LLT Classification code 10057934 Term: Diabetic macular edema

Intervention(s)

Trade Name: Lucentis
Product Name: Lucentis
Product Code: RFB002D
Pharmaceutical Form: Solution for injection

Primary Outcome(s)

Secondary Objective: Secondary objectives are
•to evaluate whether ranibizumab (0.5 mg) as adjunctive or mono-therapy is superior to laser treatment
-in the number of patients with visual acuity above 73 letters and
-in the number of patients with improvement in BCVA.
•to evaluate the time course of BCVA changes on ranibizumab (0.5 mg) adjunctive and mono-therapy relative to laser treatment
•to evaluate the effects of ranibizumab (0.5 mg) adjunctive and mono-therapy on central retinal thickness and other anatomical changes relative to laser treatment
•to evaluate the effects of ranibizumab (0.5 mg) adjunctive and mono-therapy on patient-reported outcomes (PROs) relative to laser treatment
•to evaluate the safety of intravitreal injections of ranibizumab (0.5 mg) as adjunctive and mono-therapy in patients with DME overall and relative to laser treatment.

Main Objective: The primary objective of this study is to demonstrate superiority of ranibizumab 0.5 mg as adjunctive or mono-therapy to laser treatment in the mean change from baseline in BCVA over a 12-month treatment period.

Primary end point(s): The primary variable will be the difference between the average level of BCVA (letters) over all monthly post-baseline assessments from Month 1 to Month 12 and the baseline level of BCVA.

Secondary ID(s)

RFB002D2301

2007-004877-24-FR