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 (RESTORE)

March 26, 2013 updated by: Novartis

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

345

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ranibizumab 0.5 mg

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received sham laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.
Drug: Ranibizumab
0.5 mg ranibizumab administered by intravitreal injection.
Procedure: Laser
Laser photocoagulation treatment
Procedure: Sham laser
Sham to laser procedure.
Experimental: Ranibizumab 0.5 mg + laser

Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Patients also received active laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.
Drug: Ranibizumab
0.5 mg ranibizumab administered by intravitreal injection.
Procedure: Laser
Laser photocoagulation treatment
Active Comparator: Laser

Laser photocoagulation treatment was administered on Day 1 and at intervals of at least 3 months, if deemed necessary by the physician. Patients also received monthly sham intravitreal injection in the study eye for 3 consecutive months. After the third injection, treatment was suspended if either one of the following criteria was met:

Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits.

Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes.

In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy.
Drug: Ranibizumab
0.5 mg ranibizumab administered by intravitreal injection.
Procedure: Laser
Laser photocoagulation treatment
Drug: Sham to ranibizumab
Sham to ranibizumab administered as an intravitreal injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: Baseline through the end of study (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)
Extension Study: Percentage of Participants With Ocular Adverse Events (AEs) in the Study Eye in the 24 Month Extension Study
Time Frame: Extension baseline (Month 12 -end of core study) to Month 36 (end of extension study) [24 Months]

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]
Extension Study: Percentage of Participants With Non-Ocular Adverse Events (AEs) in the 24 Month Extension Study
Time Frame: Extension baseline (Month 12 -end of core study) to Month 36 (end of extension study) [24 Months]

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]

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Core Study: Categorized Change in Visual Acuity (Letters) of the Study Eye From Baseline at Month 12
Time Frame: Baseline 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 to Month 12
Core Study: Mean Change From Baseline in Visual Acuity (Letters) of the Study Eye Over Time
Time Frame: Baseline 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 to Month 12
Core Study: Mean Change From Baseline at Month 12 in Central Retinal Thickness of the Study Eye
Time Frame: Baseline to Month 12
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
Core Study: Mean Change From Baseline in Patient-reported Visual Functioning
Time Frame: Baseline to Month 12
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
Extension Study: Percentage of Participants With Ocular Adverse Events (AEs) in the Study Eye in the 36 Months of the Core and Extension Studies
Time Frame: Core baseline (Day 1 of the core study) to Month 36 (end of extension study) [36 months]

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]
Extension Study: Percentage of Participants With Non-Ocular Adverse Events (AEs) in the 36 Months of the Core and Extension Studies
Time Frame: Core baseline (Day 1 of the core study) to Month 36 (end of extension study) [36 Months]

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]
Extension Study: Mean Change From Extension Study Baseline in Best Corrected Visual Acuity (BCVA) at Month 36
Time Frame: Extension baseline (Month12 -end of core study), Month 36 (end of extension study)
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)
Extension Study: Mean Change From Core Study Baseline in Best Corrected Visual Acuity (BCVA) at Month 36
Time Frame: Core baseline (Day 1 of the core study), Month 36 (end of extension study)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2008

Primary Completion (Actual)

January 1, 2010

Study Completion (Actual)

January 1, 2012

Study Registration Dates

First Submitted

May 27, 2008

First Submitted That Met QC Criteria

May 30, 2008

First Posted (Estimate)

June 2, 2008

Study Record Updates

Last Update Posted (Estimate)

April 1, 2013

Last Update Submitted That Met QC Criteria

March 26, 2013

Last Verified

March 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRFB002D2301
  • EUDRACT: 2007-004877-24

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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