Ranibizumab for Edema of the Macula in Diabetes: Protocol 3 With High Dose - the READ 3 Study (READ 3)

• ClinicalTrials.gov Identifier: NCT01077401
• Recruitment Status: Completed
• First Posted: March 1, 2010
• Results First Posted: April 28, 2017
• Last Update Posted: April 28, 2017
• Sponsor: Johns Hopkins University
• Collaborator: Juvenile Diabetes Research Foundation
• Information provided by (Responsible Party): Johns Hopkins University

Study Description

Brief Summary:

The purpose of this study is to investigate the safety, tolerability, bioactivity, and dose response of two different dosages (0.5 mg and 2.0 mg) of ranibizumab (RBZ) in patients with diabetic macular edema (DME).

Condition or disease	Intervention/treatment	Phase
Diabetic Macular Edema	Drug: Ranibizumab; Drug: ranibizumab	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 152 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Ranibizumab for Edema of the Macula in Diabetes: Protocol 3 With High Dose - the READ 3 Study
• Study Start Date: February 2010
• Actual Primary Completion Date: March 2012
• Actual Study Completion Date: March 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ranibizumab 0.5mg; Intravitreal injections of ranibizumab 0.5mg dose for six monthly treatments then additional treatments with ranibizumab 0.5mg dose if the subject meets re-treatment criteria.	Drug: Ranibizumab; Intravitreal injections of ranibizumab 0.5mg dose for six monthly treatments then additional treatments with ranibizumab 0.5mg dose if the subject meets re-treatment criteria.; Other Name: lucentis
Experimental: Ranibizumab 2.0 mg; Intravitreal injections of ranibizumab 2.0 mg dose for six monthly treatments then additional treatments with ranibizumab 2.0 mg dose if the subject meets re-treatment criteria.	Drug: ranibizumab; Intravitreal injections of ranibizumab 2.0 mg dose for six monthly treatments then additional treatments with ranibizumab 2.0 mg dose if the subject meets re-treatment criteria.; Other Name: lucentis high-dose

Outcome Measures

Primary Outcome Measures :

1. Deaths Due to Myocardial Infarction [ Time Frame: 6 Months ]

Secondary Outcome Measures :

1. Mean Change in Best Corrected Visual Acuity From Baseline to Month 6 [ Time Frame: baseline 6 Months ]
   Mean change in best corrected visual acuity (BCVA) (ETDRS) at 4 meters in the study eye over time through month 6.
2. Mean Change in Retinal Thickness at Month 6 [ Time Frame: baseline to6 Months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Signed informed consent and authorization of use and disclosure of protected health information

• Age ≥18 years
• Diagnosis of diabetes mellitus (type 1 or type 2)
• Serum HbA1c ≥ 5.5% within 12 months of randomization. Retinal thickening secondary to diabetes mellitus (diabetic macular edema) involving the center of the fovea
• Diagnosis must be confirmed by fluorescein angiography and OCT images
• Foveal thickness of ≥ 250 μm,
• Best corrected visual acuity score in the study eye of 20/40 to 20/320 inclusive (Snellen equivalents using the ETDRS protocol at a distance of 4 meters). The non-study eye must be ≥ 20 letters (approximate Snellen equivalent 20/400).
• In the opinion of the investigator, decreased vision in the study eye is due to foveal thickening from DME and not from other obvious causes of decreased vision If a female of childbearing potential, a negative pregnancy test and commitment to the use of at least two forms of effective contraception (birth control) for the duration of the study are necessary.

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, bevacizumab, anecortave acetate, protein kinase C inhibitor, etc.) within 2 months of study entry
• Proliferative diabetic retinopathy in the study eye, with the exceptions of
• Inactive, fibrotic proliferative diabetic retinopathy that has regressed following panretinal 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 optical coherence tomography (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
• Cataract surgery in the study eye within 3 months of study entry; Yttrium-Aluminum- Garnet (YAG) laser capsulotomy within 1 month 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 ≥30 mm Hg despite treatment with anti-glaucoma medications)
• Blood pressure exceeding 180/100 (sitting) during the screening period
• Uncontrolled diabetes mellitus, as evidenced by glycosylated hemoglobin (HbA1c) value >13%
• Renal failure requiring dialysis or renal transplant
• Premenopausal women unwilling to commit to adequate contraception
• History of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use an investigational drug, might affect interpretation of the results of the study, or render the subject at high risk from treatment complications
• International normalized ratio (INR) ≥ 3.0 (e.g. due to current treatment with warfarin). The use of aspirin or other anticoagulants is not an exclusion
• History of cerebral vascular accident, myocardial infarction, transient ischemic attacks within 3 months of study enrollment.
• Have a history of hypersensitivity to ranibizumab or any of its components
• Have the presence of active malignancy, including lymphoproliferative disorders. Subjects with a history of fully resolved basal or squamous cell skin cancer may be enrolled.

Other

• Inability to comply with study or follow-up procedures
• 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

Contacts and Locations

Locations

United States, California

Retina Vitreous Associates

Beverly Hills, California, United States, 90211

University of California San Diego

LaJolla, California, United States, 92037

Doheny Eye Institute

Los Angeles, California, United States, 90033

East Bay Retina Institute

Oakland, California, United States, 94609

Retina Macula Institute

Torrance, California, United States, 90503

United States, Florida

Retina Group of Florida

Fort Lauderdale, Florida, United States, 33334

United States, Hawaii

Retina Institute of Hawaii

Honolulu, Hawaii, United States, 96815

United States, Illinois

Illinois Retina Associates

Joliet, Illinois, United States, 60435

United States, Kansas

University of Kansas

Prairie Village, Kansas, United States, 66208

United States, Maryland

Johns Hopkins University Wilmer Eye Institute

Baltimore, Maryland, United States, 21287

United States, Pennsylvania

Eye Care Specialists

Kingston, Pennsylvania, United States, 18704

United States, South Dakota

Black Hills Eye Institute

Rapid City, South Dakota, United States, 57701

United States, Texas

Texas Retina Associates

Arlington, Texas, United States, 76012

Sponsors and Collaborators

Johns Hopkins University

Juvenile Diabetes Research Foundation

Investigators

• Principal Investigator: Diana V Do, MD; Truhlsen Eye Institute, University of Nebraska Medical Center

More Information

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT01077401
• Other Study ID Numbers: NA_00034586
• First Posted: March 1, 2010
• Results First Posted: April 28, 2017
• Last Update Posted: April 28, 2017
• Last Verified: March 2017

Keywords provided by Johns Hopkins University:

Diabetic; edema; DME

Additional relevant MeSH terms:

Macular Edema; Edema; Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases; Ranibizumab; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Antineoplastic Agents