Safety and Efficacy of Ranibizumab for Diabetic Macular Edema

Study Overview
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Brief Summary
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The primary objective of the study is to assess the ocular and systemic adverse events of ranibizumab (Lucentis)for DME (diabetic macular edema) following previous treatment with intravitreal bevacizumab (Avastin).

Detailed Description
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This is an open-label, Phase I/II study of intravitreally administered 0.3mg ranibizumab (Lucentis) in subjects with DME (diabetic macular edema) previously treated with intravitreal bevacizumab (Avastin) with a randomized comparative dosing strategy, monthly vs treat-and-extend. Thirty patients total will be enrolled in the study, 15 in each group. This study will have a 1-year treatment period. The recruitment period will occur over 1 year with total potential study duration of 2 years.

Official Title
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Safety and Efficacy of Intravitreal Ranibizumab for Diabetic Macular Edema Previously Treated With Intravitreal Bevacizumab: A Randomized Dual Arm Comparative Dosing Trial

Conditions
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Diabetic Macular Edema

Intervention / Treatment
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* Drug: Ranibizumab
* Drug: Ranibizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects will be eligible if the following criteria are met: Ability to provide written informed consent and comply with study assessments for the full duration of the study Age > 18 years ETDRS best-corrected visual acuity of 20/25 to 20/320 in the study eye Willing, committed, and able to return for ALL clinic visits and complete all study related procedures At least 6 previous bevacizumab injections for diabetic macular edema in the last 12 months in the study eye. At least 2 bevacizumab injections within 10 weeks and the most recent bevacizumab injection within 6 weeks of baseline study visits in the study eye. Persistent foveal-involving diabetic macular edema based on presence of intraretinal and/or subretinal fluid by SDOCT in the foveal center at study entry in the study eye. Exclusion Criteria: Subjects who meet any of the following criteria will be excluded from this study: Pregnancy (positive pregnancy test) or lactation Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an IUD (intrauterine device), or contraceptive hormone implant or patch. Intravitreal steroid or periocular steroid treatment within 3 months of study entry in the study eye. Focal/grid laser photocoagulation treatment within 3 months of study entry in the study eye. Panretinal photocoagulation treatment within 3 months of study entry in the study eye. Prior vitrectomy in the study eye History of retinal detachment in the study eye Prior trabeculectomy or other filtration surgery in the study eye Active intraocular inflammation in either eye Active ocular or periocular infection in either eye Active scleritis or episcleritis in either eye History of any other retinal vascular disease (e.g., retinal vein occlusion, retinal artery occlusion) in the study eye. Coexistent retinal disease other than diabetic retinopathy (e.g., AMD (age related macular degeneration), inherited retinal disease) in the study eye. Intraocular surgery within 3 months of study entry in the study eye. History of corneal transplant or corneal dystrophy in the study eye. Significant media opacities in study eye which may interfere with visual acuity in the study eye. Participation as a subject in any clinical study within 3 months of study entry. History of allergy to topical iodine Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated Participation in another simultaneous medical investigation or trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Group I - Monthly<br>Enrolled subjects will receive multiple open-label intravitreal injections of 0.3 mg ranibizumab administered every 28 days (+/- 7 days from the last treatment) for 12 months in the monthly group. | Drug: Ranibizumab<br>* Monthly injections of Intravitreal Ranibizumab 0.3 mg for 12 months in patients previously treated with Avastin for Diabetic Macular Edema.<br>* Other names: Lucentis;|
| Other: Group II - Treat-and-Extend<br>Enrolled subjects will initially receive 3 loading doses of open-label Ranibizumab 0.3 mg given via intravitreal injection every 28 days (+/- 7 days from the last treatment). After the third loading dose, the follow-up interval is determined by the Principal Investigator based on OCT results as stated in the protocol. The follow-up interval is increased by 2 weeks (+/- 7 days) at each visit up to a maximum interval of 12 weeks (+/- 7 days). There is criteria built into the protocol in case a reduction in the follow-up intervals becomes necessary based upon worsening OCT results. | Drug: Ranibizumab<br>* Three Monthly injections of Intravitreal Ranibizumab 0.3 mg in patients previously treated with Avastin for Diabetic Macular Edema. Then follow-up visits may be extended by 2 weeks for a total of 12 months.<br>* Other names: Lucentis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Non-severe Ocular Adverse Events | As identified by eye examination (including visual acuity testing), identified by physical examination, subject reporting, and changes in vital signs. These outcome measures are also included in more detail in the adverse event section of the results. | 12 months | 
| Number of Participants With Severe Ocular Adverse Events | As identified by eye examination (including visual acuity testing), identified by physical examination, subject reporting, and changes in vital signs. | 12 months | 
| Number of Participants With Non-severe Non-ocular Adverse Event | As identified by physical examination, subject reporting, and changes in vital signs. These outcome measures are also included in more detail in the adverse event section of the results. | 12 months | 
| Number of Participants With Severe Non-ocular Adverse Event | As identified by physical examination, subject reporting, and changes in vital signs. These outcome measures are also included in more detail in the adverse event section of the results. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in BCVA | Mean change in best-corrected visual acuity as assessed by the number of letters read correctly on the electronic ETDRS eye chart from baseline to months 6 and 12. | Months 6 and 12 | 
| Mean Change in Central Foveal Thickness | Mean absolute change from baseline central foveal thickness at months 6 and 12 as measured by SDOCT (defined as the average thickness within the central 1 mm subfield) | Months 6 and 12 | 
| Anatomically Dry Eyes by SDOCT | Number of participants with an anatomically dry study eye by SDOCT at months 6 and 12 | Months 6 and 12 | 
| Gain in Vision Greater Than or Equal to 15 Letters | Number of participants that gained greater than or equal to 15 letters of vision in their study eye at months 6 and 12. | Months 6 and 12 | 
| Loss in Vision Greater Than or Equal to 15 Letters | Number of participants that lost greater than or equal to 15 letters of vision in their study eye at months 6 and 12. | Months 6 and 12 | 
| Participants With BCVA at 20/40 or Better | Number of participants with 20/40 or better best-corrected visual acuity in their study eye at months 6 and 12. | Months 6 and 12 | 
| Number of Participants With Angiographic Leakage | Number of participants with angiographic leakage in their study eye measured from baseline to months 3, 6 and 12 (i.e. presence of leakage). | 3, 6 and 12 months | 
| Number of Participants With Nonperfusion | Number of participants with peripheral nonperfusion in their study eye from baseline to months 3, 6, and 12 (i.e. presence of ischemia). | 3, 6 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Macular Edema