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The Ranibizumab for Edema of the mAcula in Diabetes-2 (READ-2) Study

Phase 2
Completed
Conditions
Diabetic Macular Edema
Interventions
Procedure: Laser photocoagulation
Registration Number
NCT00407381
Lead Sponsor
Johns Hopkins University
Brief Summary

This study is being done to see if the investigational drug Ranibizumab (RBZ) given by injection into the eye, is safe and effective to use in people with diabetic macular edema (DME). The investigators want to compare RBZ to laser treatment which is the current standard way to treat DME.

RBZ blocks a growth factor that is thought to be involved in the formation of abnormal blood vessels that cause loss of vision in patients with DME.

Detailed Description

The READ-2 Study is a phase 2 randomized, multi-center clinical trial to be conducted under an investigator-initiated investigational new drug (IND). The study aims to enroll 126 patients, who will be randomized into 3 different groups. The primary objectives of the READ-2 Study are: (a) to obtain data on the bioactivity and dose interval effects of intravitreal ranibizumab (RBZ) alone, as well as in combination with laser photocoagulation, on retinal thickness and visual acuity in subjects with DME; and (b) to obtain additional safety and bioactivity data to aid in the design of a phase 3 clinical trial to evaluate ranibizumab as a therapeutic option for patients with DME The study consists of a 2-week screening period (Days -14 to 0), a 6-month treatment period with a primary time endpoint, and a 18-month follow-up and treatment period with secondary time endpoints. Consented subjects will enter the 14-day screening period to determine eligibility. Serum chemistry and hematology testing, urinalysis, pregnancy testing, and macular thickness measurements based on optical coherence tomography (OCT) will be performed. Screening will also include VA, ophthalmic examination and fluorescein angiography (FA) entry criteria.

Patients who have ETDRS visual acuity of 20/40 or worse, but better than or equal to 20/320 due to foveal thickening from macular edema secondary to diabetes (type 1 or 2) and who meet eligibility criteria will be eligible to enroll in the study. Baseline foveal thickness by OCT must be at least 250, which is often associated with VA of 20/40 or worse and which provides sufficient thickening so that a treatment effect is easily detectable (Nguyen et al. 2004). Approximately 126 patients with DME will be enrolled in this study from all clinical sites in the study. Every effort will be made to recruit and enroll eligible patients from men and women of all ethnic and social backgrounds. Patients who meet entry criteria will be able to enroll in the study until the quota of patients has been achieved.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
126
Inclusion Criteria

Not provided

Exclusion Criteria
  • Panretinal photocoagulation or macular photocoagulation within 3 months of study entry in the study eye
  • Use of intraocular or periocular injection of steroids in the study eye (e.g., triamcinolone) within 3 months of study entry
  • Previous participation in a study and receipt of anti-angiogenic drugs (pegaptanib sodium, ranibizumab, anecortave acetate, protein kinase C inhibitor, etc.) within 2 months of study entry
  • Eyes in which the investigators do not feel appropriate to do any additional laser photocoagulation
  • Proliferative diabetic retinopathy in the study eye, with the exceptions of inactive, fibrotic proliferative diabetic retinopathy that has regressed following pan-retinal laser photocoagulation or tufts of neovascularization elsewhere (NVE) less than one disc area with no vitreous hemorrhage
  • Vitreomacular traction or epiretinal membrane in the study eye evident biomicroscopically or by OCT
  • Structural damage to the center of the macula in the study eye likely to preclude improvement in visual acuity following the resolution of macular edema, including atrophy of the retinal pigment epithelium, subretinal fibrosis, laser scar(s), macular ischemia, or organized hard exudate plaque
  • Ocular disorders in the study eye that may confound interpretation of study results, including retinal vascular occlusion, retinal detachment, macular hole, or choroidal neovascularization of any cause (e.g., age related macular degeneration (AMD), ocular histoplasmosis, or pathologic myopia)
  • Concurrent disease in the study eye that could compromise visual acuity or require medical or surgical intervention during the first 6-month study period
  • Eyes which are likely to need cataract surgery and intraocular lens implantation within the first 6 months of the study
  • Cataract surgery in the study eye within 3 months of study entry; Yttrium-Aluminum-Garnet (YAG) laser capsulotomy within 2 months of study entry; or any other intraocular surgery within 3 months preceding Day 0.
  • History of vitreoretinal surgery in the study eye within 3 months of study entry
  • Uncontrolled glaucoma (defined as intraocular pressure greater than 30 mm Hg despite treatment with anti-glaucoma medications)
  • Uncontrolled diabetes mellitus, as evidenced by glycosylated hemoglobin (HbA1c) value greater than 12%
  • Premenopausal women not using adequate contraception
  • Any women who are pregnant
  • International normalized ratio (INR) greater than or equal to 3.0 (e.g. due to current treatment with warfarin). The use of aspirin or other anticoagulants is not an exclusion
  • History of gastrointestinal bleeding within 2 months of study enrollment
  • History of major gastrointestinal, cardiothoracic, gynecological, genitourinary, or orthopedic surgeries within 2 months of study enrollment
  • History of cerebral vascular accident, myocardial infarction, transient ischemic attacks within 6 months of study enrollment
  • Any patients who are on renal dialysis

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
LaserLaser photocoagulationLaser photocoagulation
Laser with RanibizumabRanibizumabLaser following intravitreal injection of RBZ
Laser with RanibizumabLaser photocoagulationLaser following intravitreal injection of RBZ
RanibizumabRanibizumabRanibizumab (RBZ) intravitreal injection alone
Primary Outcome Measures
NameTimeMethod
Mean Change in Best Corrected Visual Acuity (BCVA) at Month 66 months

Mean change of best corrected visual acuity letters (BCVA) at month 6

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (20)

East Bay Retina Consultants

🇺🇸

Oakland, California, United States

Retina Institute of California

🇺🇸

Pasadena, California, United States

New England Retina Consultants, PC

🇺🇸

West Springfield, Massachusetts, United States

Black Hills Regional Eye Institute

🇺🇸

Rapid City, South Dakota, United States

Retina-Vitreous Associates Medical Group

🇺🇸

Beverly Hills, California, United States

Southern New England Retina Associates

🇺🇸

Providence, Rhode Island, United States

Ophthalmic Consultants of Boston

🇺🇸

Boston, Massachusetts, United States

Retinal Consultants of Nevada

🇺🇸

Las Vegas, Nevada, United States

Duke Eye Center

🇺🇸

Durham, North Carolina, United States

Retinal Consultants of Arizona

🇺🇸

Phoenix, Arizona, United States

University of Southern California

🇺🇸

Los Angeles, California, United States

University of California, San Francisco

🇺🇸

San Francisco, California, United States

Eye Care Specialists, PC

🇺🇸

Kingston, Pennsylvania, United States

Yale Eye Center

🇺🇸

New Haven, Connecticut, United States

Emory University

🇺🇸

Atlanta, Georgia, United States

Illinois Retina Associates Rush University

🇺🇸

Chicago, Illinois, United States

University of Chicago

🇺🇸

Chicago, Illinois, United States

Midwest Eye Institute

🇺🇸

Indianapolis, Indiana, United States

Wilmer Eye Institute at Johns Hopkins University School of Medicine

🇺🇸

Baltimore, Maryland, United States

University of New Mexico

🇺🇸

Albuquerque, New Mexico, United States

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