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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00687804




Registration number
NCT00687804
Ethics application status
Date submitted
27/05/2008
Date registered
2/06/2008
Date last updated
1/04/2013

Titles & IDs
Public title
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
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
Secondary ID [1] 0 0
EUDRACT: 2007-004877-24
Secondary ID [2] 0 0
CRFB002D2301
Universal Trial Number (UTN)
Trial acronym
RESTORE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetic Macular Edema 0 0
Condition category
Condition code
Eye 0 0 0 0
Diseases / disorders of the eye
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ranibizumab
Treatment: Surgery - Laser
Treatment: Surgery - Sham laser
Treatment: Drugs - Sham to ranibizumab

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.

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.

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.


Treatment: Drugs: Ranibizumab
0.5 mg ranibizumab administered by intravitreal injection.

Treatment: Surgery: Laser
Laser photocoagulation treatment

Treatment: Surgery: Sham laser
Sham to laser procedure.

Treatment: Drugs: Sham to ranibizumab
Sham to ranibizumab administered as an intravitreal injection.

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline through the end of study (Month 12)
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
Extension baseline (Month 12 -end of core study) to Month 36 (end of extension study) [24 Months]
Primary outcome [3] 0 0
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.
Timepoint [3] 0 0
Extension baseline (Month 12 -end of core study) to Month 36 (end of extension study) [24 Months]
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline to Month 12
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Baseline to Month 12
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Baseline to Month 12
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Baseline to Month 12
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
Core baseline (Day 1 of the core study) to Month 36 (end of extension study) [36 months]
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
Core baseline (Day 1 of the core study) to Month 36 (end of extension study) [36 Months]
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
Extension baseline (Month12 -end of core study), Month 36 (end of extension study)
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
Core baseline (Day 1 of the core study), Month 36 (end of extension study)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Novartis Investigative Site - Melbourne
Recruitment postcode(s) [1] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Leuven
Country [2] 0 0
Canada
State/province [2] 0 0
Ontario
Country [3] 0 0
France
State/province [3] 0 0
Paris
Country [4] 0 0
Germany
State/province [4] 0 0
Düsseldorf
Country [5] 0 0
Greece
State/province [5] 0 0
Athens
Country [6] 0 0
Hungary
State/province [6] 0 0
Budapest
Country [7] 0 0
Italy
State/province [7] 0 0
Firenze
Country [8] 0 0
Netherlands
State/province [8] 0 0
Amsterdam
Country [9] 0 0
Spain
State/province [9] 0 0
Barcelona
Country [10] 0 0
Switzerland
State/province [10] 0 0
Zurich
Country [11] 0 0
Turkey
State/province [11] 0 0
Ankara
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Upton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00687804
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications