Clinical trial NCT00687804: A 12 Month Core Study to Assess the Efficacy and Safety of Ranibizumab (Intravitreal Injections) in Patients With Visual Impairment Due to Diabetic Macular Edema and a 24 Month Open-label Extension Study
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetic Macular Edema
Keywords: DME
Diabetic
macula
edema
ranibizumab
RESTORE
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2008-06-02
Enrollment: 345
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: CRFB002D2301: The core study was designed to confirm the efficacy and safety of ranibizumab (0.5 mg) as adjunctive therapy when added to laser photocoagulation and/or mono-therapy in patients with visual impairment due to diabetic macular edema.

CRFB002D2301E1: A 24 month open-label extension study for participants who completed the 12 month core study evaluated the long-term safety and efficacy of ranibizumab (0.5 mg) as symptomatic treatment for visual impairment due to diabetic macular edema.


Eligibility criteria: Inclusion Criteria:

* Visual acuity impairment
* Diabetic macular edema in at least one eye
* Type 1 or type 2 diabetes mellitus
* Medication for the diabetes treatment must be stable for the last 3 months

Exclusion Criteria:

* Patients with uncontrolled systemic or ocular diseases
* Laser photocoagulation in the study eye for the last 3 months
* Any history of any intraocular surgery in the study eye within the past 3 months
* Blood pressure \> 160/100 mmHg

Extension Inclusion Criteria:

-Completion of the Core Study

Primary outcomes:
measure: Core Study: Difference Between the Baseline Level of Visual Acuity (Letters) of the Study Eye and the Mean Visual Acuity Averaged Over All Monthly Post-baseline Assessments From Month 1 to Month 12
timeFrame: Baseline through the end of study (Month 12)
measure: Extension Study: Percentage of Participants With Ocular Adverse Events (AEs) in the Study Eye in the 24 Month Extension Study
timeFrame: Extension baseline (Month 12 -end of core study) to Month 36 (end of extension study) [24 Months]
measure: Extension Study: Percentage of Participants With Non-Ocular Adverse Events (AEs) in the 24 Month Extension Study
timeFrame: Extension baseline (Month 12 -end of core study) to Month 36 (end of extension study) [24 Months]
Secondary outcomes:
measure: Core Study: Categorized Change in Visual Acuity (Letters) of the Study Eye From Baseline at Month 12
timeFrame: Baseline to Month 12
measure: Core Study: Mean Change From Baseline in Visual Acuity (Letters) of the Study Eye Over Time
timeFrame: Baseline to Month 12
measure: Core Study: Mean Change From Baseline at Month 12 in Central Retinal Thickness of the Study Eye
timeFrame: Baseline to Month 12
measure: Core Study: Mean Change From Baseline in Patient-reported Visual Functioning
timeFrame: Baseline to Month 12
measure: Extension Study: Percentage of Participants With Ocular Adverse Events (AEs) in the Study Eye in the 36 Months of the Core and Extension Studies
timeFrame: Core baseline (Day 1 of the core study) to Month 36 (end of extension study) [36 months]
measure: Extension Study: Percentage of Participants With Non-Ocular Adverse Events (AEs) in the 36 Months of the Core and Extension Studies
timeFrame: Core baseline (Day 1 of the core study) to Month 36 (end of extension study) [36 Months]
measure: Extension Study: Mean Change From Extension Study Baseline in Best Corrected Visual Acuity (BCVA) at Month 36
timeFrame: Extension baseline (Month12 -end of core study), Month 36 (end of extension study)
measure: Extension Study: Mean Change From Core Study Baseline in Best Corrected Visual Acuity (BCVA) at Month 36
timeFrame: Core baseline (Day 1 of the core study), Month 36 (end of extension study)
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Ontario
country: Canada
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Düsseldorf
country: Germany
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Firenze
country: Italy
facility: Novartis Investigative Site
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Zurich
country: Switzerland
facility: Novartis Investigational Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Upton
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Bressler NM, Varma R, Mitchell P, Suner IJ, Dolan C, Ward J, Ferreira A, Ehrlich JS, Turpcu A. Effect of Ranibizumab on the Decision to Drive and Vision Function Relevant to Driving in Patients With Diabetic Macular Edema: Report From RESTORE, RIDE, and RISE Trials. JAMA Ophthalmol. 2016 Feb;134(2):160-6. doi: 10.1001/jamaophthalmol.2015.4636.
citation: Mitchell P, Massin P, Bressler S, Coon CD, Petrillo J, Ferreira A, Bressler NM. Three-year patient-reported visual function outcomes in diabetic macular edema managed with ranibizumab: the RESTORE extension study. Curr Med Res Opin. 2015 Nov;31(11):1967-75. doi: 10.1185/03007995.2015.1081880. Epub 2015 Oct 6.
citation: Bressler NM, Varma R, Suner IJ, Dolan CM, Ward J, Ehrlich JS, Colman S, Turpcu A; RIDE and RISE Research Groups. Vision-related function after ranibizumab treatment for diabetic macular edema: results from RIDE and RISE. Ophthalmology. 2014 Dec;121(12):2461-72. doi: 10.1016/j.ophtha.2014.07.008. Epub 2014 Aug 20.
citation: Mitchell P, Bressler N, Tolley K, Gallagher M, Petrillo J, Ferreira A, Wood R, Bandello F; RESTORE Study Group. Patient-reported visual function outcomes improve after ranibizumab treatment in patients with vision impairment due to diabetic macular edema: randomized clinical trial. JAMA Ophthalmol. 2013 Oct;131(10):1339-47. doi: 10.1001/jamaophthalmol.2013.4592.
citation: Mitchell P, Bandello F, Schmidt-Erfurth U, Lang GE, Massin P, Schlingemann RO, Sutter F, Simader C, Burian G, Gerstner O, Weichselberger A; RESTORE study group. The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology. 2011 Apr;118(4):615-25. doi: 10.1016/j.ophtha.2011.01.031.
citation: Schmidt-Erfurth U, Lang GE, Holz FG, Schlingemann RO, Lanzetta P, Massin P, Gerstner O, Bouazza AS, Shen H, Osborne A, Mitchell P; RESTORE Extension Study Group. Three-year outcomes of individualized ranibizumab treatment in patients with diabetic macular edema: the RESTORE extension study. Ophthalmology. 2014 May;121(5):1045-53. doi: 10.1016/j.ophtha.2013.11.041. Epub 2014 Feb 1.