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-DE
• Date of registration: 28/04/2008
• 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: 22/07/2008
• 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: no Parallel group: yes Cross over: no Other: yes Other trial design description: double-masked 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. The study eye must fulfill the following criteria at Visit 1 (if both eyes are eligible, the study eye will be selected by the investigator):
•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 1 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), 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 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 the study eye (according to investigator’s judgement)
Neovascularization of the iris in study eye
8.Evidence of vitreomacular traction in study eye
9.Active proliferative diabetic retinopathy in the study eye
Ocular treatments
10.Panretinal laser photocoagulation in the study eye within 6 months prior to or during the study
11.Focal/grid laser photocoagulation in the study eye within 3 months prior to study entry
12.Treatment with anti-angiogenic drugs (pegaptanib sodium, anecortave acetate, bevacizumab, ranibizumab, etc.) or intravitreal corticosteroids in study eye within 3 months prior to randomization
13.Any intraocular surgery in the study eye within 3 months prior to randomization
14.History of vitrectomy in study eye
15.Phakic study eye with a history of intravitreal corticosteroid treatment
16.Ocular conditions in the study eye that require chronic concomitant therapy with topical ocular or systemically administered corticosteroids
Systemic conditions or treatments
17.History of stroke
18.Renal failure requiring dialysis or renal transplant OR renal insufficiency with creatinine levels > 2.0 mg/dl
19.Untreated diabetes mellitus
20.Blood pressure systolic > 160 mmHg and diastolic > 100 mmHg
21.Untreated hypertension or change in antihypertensive treatment within 3 months preceding Baseline
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.Known hypersensitivity to ranibizumab or any component of the ranibizumab formulation
Compliance/ Administrative
24.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 randomization
25. 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 par

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® 10 mg/ml Injektionslösung
Product Name: Lucentis
Product Code: RFB002
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ranibizumab
Current Sponsor code: RFB002
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

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)

2007-004877-24-FR

CRFB002D2301