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

Diabetic Macular Edema Clinical Trial

— RESTORE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00687804
• Other study ID #: CRFB002D2301
• Secondary ID: EUDRACT: 2007-00
• Status: Completed
• Phase: Phase 3
• First received: May 27, 2008
• Last updated: March 26, 2013
• Start date: May 2008
• Est. completion date: January 2012

Study information

• Verified date: March 2013
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: SwissmedicAustralia: Department of Health and Ageing Therapeutic Goods AdministrationBelgium: Federal Agency for Medicinal Products and Health ProductsGermany: Paul-Ehrlich-InstitutSpain: Spanish Agency of MedicinesFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Greece: National Organization of MedicinesHungary: National Institute of PharmacyNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Other known NCT identifiers

• NCT00906464

Recruitment information / eligibility

• Status: Completed
• Enrollment: 345
• Est. completion date: January 2012
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetic Macular Edema
• Edema
• Macular Edema

Intervention

Drug:
• Ranibizumab
0.5 mg ranibizumab administered by intravitreal injection.

Procedure:
• Laser
Laser photocoagulation treatment
• Sham laser
Sham to laser procedure.

Drug:
• Sham to ranibizumab
Sham to ranibizumab administered as an intravitreal injection.

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Melbourne
Belgium	Novartis Investigative Site	Leuven
Canada	Novartis Investigative Site	Ontario
France	Novartis Investigative Site	Paris
Germany	Novartis Investigative Site	Düsseldorf
Greece	Novartis Investigative Site	Athens
Hungary	Novartis Investigative Site	Budapest
Italy	Novartis Investigative Site	Firenze
Netherlands	Novartis Investigative Site	Amsterdam
Spain	Novartis Investigative Site	Barcelona
Switzerland	Novartis Investigational Site	Zurich
Turkey	Novartis Investigative Site	Ankara
United Kingdom	Novartis Investigative Site	Upton

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Countries where clinical trial is conducted

Australia,  Belgium,  Canada,  France,  Germany,  Greece,  Hungary,  Italy,  Netherlands,  Spain,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Visual acuity (VA) was assessed on both eyes during every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters.	Baseline through the end of study (Month 12)	No
Primary	Extension Study: Percentage of Participants With Ocular Adverse Events (AEs) in the Study Eye in the 24 Month Extension Study	Participants with ocular (occurring in the eye) serious adverse events (SAEs) and non-serious AEs in the study eye. The study eye is the eye that received the treatment. AEs are the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to study drug. A serious adverse event is defined as an event that is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, requires inpatient hospitalization or prolongation of existing hospitalization or is medically significant.; Additional information about adverse events can be found in the Adverse Event section.	Extension baseline (Month 12 -end of core study) to Month 36 (end of extension study) [24 Months]	No
Primary	Extension Study: Percentage of Participants With Non-Ocular Adverse Events (AEs) in the 24 Month Extension Study	Participants with non-ocular (not occurring in the eye) serious adverse events (SAEs) and non-serious AEs. AEs are the appearance or worsening of of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to study drug. A serious adverse event is defined as an event that is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, requires inpatient hospitalization or prolongation of existing hospitalization or is medically significant.; Additional information about adverse events can be found in the Adverse Event section.	Extension baseline (Month 12 -end of core study) to Month 36 (end of extension study) [24 Months]	No
Secondary	Core Study: Categorized Change in Visual Acuity (Letters) of the Study Eye From Baseline at Month 12	Visual acuity (VA) was assessed on both eyes during every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters.	Baseline to Month 12	No
Secondary	Core Study: Mean Change From Baseline in Visual Acuity (Letters) of the Study Eye Over Time	Visual acuity (VA) was assessed on both eyes during every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters.	Baseline to Month 12	No
Secondary	Core Study: Mean Change From Baseline at Month 12 in Central Retinal Thickness of the Study Eye	Retinal thickness was measured using Optical Coherence Tomography (OCT). The images were reviewed by a central reading center to ensure a standardized evaluation.	Baseline to Month 12	No
Secondary	Core Study: Mean Change From Baseline in Patient-reported Visual Functioning	The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) was used to measure a patient's subjective assessment of vision-related quality of life. The 12 subscales in the VFQ-25 are general health, general vision, ocular pain, near activities, distance activities, social function, mental health, role difficulties, dependency, driving, color vision, and peripheral vision. The scores on the subscales were added together for a total score, which ranged from 0 to 100. A higher score indicated improvement in quality of life due to vision function.	Baseline to Month 12	No
Secondary	Extension Study: Percentage of Participants With Ocular Adverse Events (AEs) in the Study Eye in the 36 Months of the Core and Extension Studies	Participants with ocular (occurring in the eye) serious adverse events (SAEs) and non-serious AEs in the study eye. The study eye is the eye that received the treatment. AEs are the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to study drug. A serious adverse event is defined as an event that is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, requires inpatient hospitalization or prolongation of existing hospitalization or is medically significant.; Additional information about adverse events can be found in the Adverse Event section.	Core baseline (Day 1 of the core study) to Month 36 (end of extension study) [36 months]	No
Secondary	Extension Study: Percentage of Participants With Non-Ocular Adverse Events (AEs) in the 36 Months of the Core and Extension Studies	Participants with non-ocular (not occurring in the eye) serious adverse events (SAEs) and non-serious AEs. AEs are the appearance or worsening of of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to study drug. A serious adverse event is defined as an event that is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, requires inpatient hospitalization or prolongation of existing hospitalization or is medically significant.; Additional information about Adverse Events can be found in the Adverse Event section.	Core baseline (Day 1 of the core study) to Month 36 (end of extension study) [36 Months]	No
Secondary	Extension Study: Mean Change From Extension Study Baseline in Best Corrected Visual Acuity (BCVA) at Month 36	Visual acuity (VA) was assessed on both eyes during every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters. An increase in the number of letters read correctly indicates improvement.	Extension baseline (Month12 -end of core study), Month 36 (end of extension study)	No
Secondary	Extension Study: Mean Change From Core Study Baseline in Best Corrected Visual Acuity (BCVA) at Month 36	Visual acuity (VA) was assessed on both eyes during every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters. An increase in the number of letters read correctly indicates improvement.	Core baseline (Day 1 of the core study), Month 36 (end of extension study)	No