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
Results First Received: January 19, 2011  
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
Condition: Diabetic Macular Edema
Interventions: Drug: Ranibizumab
Procedure: Laser
Procedure: Sham laser
Drug: Sham to ranibizumab

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants who completed the 12 month randomized core study CRFB002D2301 were eligible to participate in the 24 month open-label extension study CRFB002D2301E1. The reporting groups for the participants in the extension study are according to their assigned treatment groups in the core study.

Reporting Groups
  Description
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.

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 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.

Laser

Active laser photocoagulation treatment was administered on Day 1 and at intervals of at least 3 months, if deemed necessary by the evaluating 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.


Participant Flow for 2 periods

Period 1:   Core Study
    Ranibizumab 0.5 mg     Ranibizumab 0.5 mg + Laser     Laser  
STARTED     116     118     111  
COMPLETED     102     103     98  
NOT COMPLETED     14     15     13  
Adverse Event                 5                 3                 3  
Abnormal laboratory value(s)                 1                 0                 0  
Lack of Efficacy                 1                 1                 1  
Withdrawal by Subject                 4                 7                 7  
Lost to Follow-up                 0                 1                 0  
Death                 2                 2                 2  
Protocol Violation                 1                 1                 0  

Period 2:   Open-Label Extension Study
    Ranibizumab 0.5 mg     Ranibizumab 0.5 mg + Laser     Laser  
STARTED     83     83     74  
Did Not Receive Ranibizumab in Extension     16     21     15  
COMPLETED     73     72     63  
NOT COMPLETED     10     11     11  
Adverse Event                 2                 2                 2  
Subject withdrew consent                 3                 4                 4  
Lost to Follow-up                 2                 1                 2  
Administrative problems                 1                 1                 0  
Death                 2                 3                 3  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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.

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.

Laser

Laser photocoagulation treatment was administered on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating 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.

Total Total of all reporting groups

Baseline Measures
    Ranibizumab 0.5 mg     Ranibizumab 0.5 mg + Laser     Laser     Total  
Number of Participants  
[units: participants]
  116     118     111     345  
Age  
[units: years]
Mean ± Standard Deviation
  62.9  ± 9.29     64.0  ± 8.15     63.5  ± 8.81     63.5  ± 8.75  
Age, Customized  
[units: Participants]
       
< 55 years     24     14     13     51  
55 - <65 years     41     42     53     136  
65 - <75 years     40     53     31     124  
>=75 years     11     9     14     34  
Gender  
[units: participants]
       
Female     43     48     53     144  
Male     73     70     58     201  



  Outcome Measures
  Show All Outcome Measures

1.  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   [ Time Frame: Baseline through the end of study (Month 12) ]

2.  Primary:   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] ]

3.  Primary:   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] ]

4.  Secondary:   Core Study: Categorized Change in Visual Acuity (Letters) of the Study Eye From Baseline at Month 12   [ Time Frame: Baseline to Month 12 ]

5.  Secondary:   Core Study: Mean Change From Baseline in Visual Acuity (Letters) of the Study Eye Over Time   [ Time Frame: Baseline to Month 12 ]

6.  Secondary:   Core Study: Mean Change From Baseline at Month 12 in Central Retinal Thickness of the Study Eye   [ Time Frame: Baseline to Month 12 ]

7.  Secondary:   Core Study: Mean Change From Baseline in Patient-reported Visual Functioning   [ Time Frame: Baseline to Month 12 ]

8.  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   [ Time Frame: Core baseline (Day 1 of the core study) to Month 36 (end of extension study) [36 months] ]

9.  Secondary:   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] ]

10.  Secondary:   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) ]

11.  Secondary:   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) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862 778-8300


No publications provided by Novartis

Publications automatically indexed to this study:

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