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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT00687804
First received: May 27, 2008
Last updated: March 26, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Diabetic Macular Edema
Drug: Ranibizumab
Procedure: Laser
Procedure: Sham laser
Drug: Sham to ranibizumab
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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] ] [ Designated as safety issue: No ]

    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 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] ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Core Study: Categorized Change in Visual Acuity (Letters) of the Study Eye From Baseline at Month 12 [ Time Frame: Baseline to Month 12 ] [ Designated as safety issue: No ]
    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.

  • Core Study: Mean Change From Baseline in Visual Acuity (Letters) of the Study Eye Over Time [ Time Frame: Baseline to Month 12 ] [ Designated as safety issue: No ]
    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.

  • Core Study: Mean Change From Baseline at Month 12 in Central Retinal Thickness of the Study Eye [ Time Frame: Baseline to Month 12 ] [ Designated as safety issue: No ]
    Retinal thickness was measured using Optical Coherence Tomography (OCT). The images were reviewed by a central reading center to ensure a standardized evaluation.

  • Core Study: Mean Change From Baseline in Patient-reported Visual Functioning [ Time Frame: Baseline to Month 12 ] [ Designated as safety issue: No ]
    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.

  • 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] ] [ Designated as safety issue: No ]

    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 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] ] [ Designated as safety issue: No ]

    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 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) ] [ Designated as safety issue: No ]
    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 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) ] [ Designated as safety issue: No ]
    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.


Enrollment: 345
Study Start Date: May 2008
Study Completion Date: January 2012
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00687804

Locations
Australia
Novartis Investigative Site
Melbourne, Australia
Belgium
Novartis Investigative Site
Leuven, Belgium
Canada
Novartis Investigative Site
Ontario, Canada
France
Novartis Investigative Site
Paris, France
Germany
Novartis Investigative Site
Düsseldorf, Germany
Greece
Novartis Investigative Site
Athens, Greece
Hungary
Novartis Investigative Site
Budapest, Hungary
Italy
Novartis Investigative Site
Firenze, Italy
Netherlands
Novartis Investigative Site
Amsterdam, Netherlands
Spain
Novartis Investigative Site
Barcelona, Spain
Switzerland
Novartis Investigational Site
Zurich, Switzerland
Turkey
Novartis Investigative Site
Ankara, Turkey
United Kingdom
Novartis Investigative Site
Upton, United Kingdom
Sponsors and Collaborators
Novartis
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00687804     History of Changes
Obsolete Identifiers: NCT00906464
Other Study ID Numbers: CRFB002D2301, EUDRACT: 2007-004877-24
Study First Received: May 27, 2008
Results First Received: January 19, 2011
Last Updated: March 26, 2013
Health Authority: Switzerland: Swissmedic
Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Germany: Paul-Ehrlich-Institut
Spain: Spanish Agency of Medicines
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Greece: National Organization of Medicines
Hungary: National Institute of Pharmacy
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:
DME
Diabetic
macula
edema
ranibizumab
RESTORE

Additional relevant MeSH terms:
Edema
Macular Edema
Signs and Symptoms
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases

ClinicalTrials.gov processed this record on September 16, 2014