Ranibizumab in Residual Diabetic Macular Edema Following Previous Anti-VEGF Therapy

This study is designed to confirm that the investigational drug Ranibizumab given by injection into the eye is safe and effective to use in people with diabetic macular edema (DME).

Study Overview

• Status: Completed
• Conditions: Diabetic Macular Edema
• Intervention / Treatment: Drug: Ranibizumab; Drug: Ranibizumab

Detailed Description

Ranibizumab works by blocking Vascular Endothelial Growth Factor (VEGF), a substance which is found in eyes with diabetic eye disease and which causes leakage from blood vessels. Several studies have suggested that eyes with DME may have very high levels of VEGF; therefore, Ranibizumab may be helpful in blocking VEGF and decreasing DME.

Ranibizumab has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of wet age-related macular degeneration (AMD) and Retinal Vein Occlusion at the dose amount of 0.5 mg. Ranibizumab has not been approved for use in subjects with DME.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • Vitreo-Retinal Associates, PC

Participation Criteria

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:

• Subjects will be eligible if the following criteria are met:

  1. Age > 18 years
  2. Diagnosis of diabetes mellitus (type 1 or 2)
  3. Residual edema as determined by mean foveal thickness on Cirrus OCT > 300 microns and leakage seen on FA at baseline
  4. Clinical evidence of retinal thickening due to macular edema involving the center of the macula, associated with diabetic retinopathy.
  5. Previous history of at least 4 or more consecutive anti-VEGF intravitreal injections of Pegaptanib sodium or Bevacizumab (consecutive injections administered no more than 6 weeks apart in the last year) for the treatment of diabetic macular edema.
  6. Previous history of focal laser and/or intravitreal steroid injection for the treatment of diabetic macular edema.
  7. BCVA of 20/32-20/400 (ETDRS)
  8. Media clarity, pupillary dilation and patient cooperation sufficient to allow OCT testing and retinal photography

Exclusion Criteria:

1. Pregnancy (positive pregnancy test) or known to be pregnant; also pre-menopausal 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, or contraceptive hormone implant or patch.
2. Participation in another ocular investigation or trial simultaneously.
3. Systemic use of anti-VEGF within 3 months prior to day 0.
4. Previous intravitreal ranibizumab within 3 months prior to day 0
5. Blood pressure > 180/110 (systolic above 180 OR diastolic above 110)
6. Any condition that, in the opinion of the investigator, would preclude participation in the study (e.g. chronic alcoholism, drug abuse).
7. Evidence of vitreoretinal interface abnormality after ocular exam or OCT that may be contributing to the macular edema.
8. An eye that, in the investigator's opinion, has no chance of improving in visual acuity following resolution of macular edema (e.g. presence of subretinal fibrosis, ischemic maculopathy or geographic atrophy).
9. Presence of another ocular condition that may affect the visual acuity or macular edema during the course of the study (e.g. AMD, uveitis, Irvine-Gass).
10. Evidence of active neovascularization of the iris or retina.
11. Evidence of central atrophy or fibrosis in the study eye.
12. Presence of substantial cataract, one that might decrease the vision by 3 or more lines of vision at sometime during the study.
13. History of vitreous surgery in the study eye.
14. History of cataract surgery within 6 months of enrollment.
15. History of YAG capsulotomy within 2 months of enrollment.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1:The PRN Group; You will receive 6 monthly intravitreal injections of 0.5% Ranibizumab administered about every 28 days. It is possible you may receive additional injections into the study eye for the next six months if certain criteria is met.	Drug: Ranibizumab; A 0.5mg intravitreal injection of Ranibizumab will be administered to subjects. Subjects will receive 6 monthly consecutive ranibizumab injections. Study visits will be scheduled to occur every 28 days relative to the date of the first injection; Other Names: lucentis; Drug: Ranibizumab; A 0.5mg intravitreal injection of Ranibizumab will be administered to subjects. Subjects will receive 12 monthly consecutive ranibizumab injections. Study visits will be scheduled to occur every 28 days relative to the date of the first injection; Other Names: lucentis
Active Comparator: arm 2:The Monthly Group: You will receive 12 monthly intravitreal injections of 0.5% Ranibizumab administered every 28 days.	Drug: Ranibizumab; A 0.5mg intravitreal injection of Ranibizumab will be administered to subjects. Subjects will receive 6 monthly consecutive ranibizumab injections. Study visits will be scheduled to occur every 28 days relative to the date of the first injection; Other Names: lucentis; Drug: Ranibizumab; A 0.5mg intravitreal injection of Ranibizumab will be administered to subjects. Subjects will receive 12 monthly consecutive ranibizumab injections. Study visits will be scheduled to occur every 28 days relative to the date of the first injection; Other Names: lucentis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Visual Acuity Scores at Month 12 Compared to Baseline	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Resolution of residual edema compared to baseline as determined by mean foveal thickness on Cirrus OCT 300 microns at Month 6 and Month 12.	12 months

Collaborators and Investigators

• Sponsor: Vitreo-Retinal Associates, PC
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Frank J McCabe, M.D., Vitreo-Retinal Associates, PC; Study Director: Marie V Lampson, Vitreo-Retinal Associates, PC

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: November 3, 2011
• First Submitted That Met QC Criteria: November 10, 2011
• First Posted (Estimate): November 16, 2011

Study Record Updates

• Last Update Posted (Estimate): March 14, 2014
• Last Update Submitted That Met QC Criteria: March 13, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: Diabetic; Edema; Ranibizumab; anti-VEGF; Macular
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema; Edema; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab
• Other Study ID Numbers: ML27906