Diabetic Macular Edema
Conditions
Keywords
Diabetic, edema, DME
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).
Interventions
DRUGRanibizumab
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.
DRUGranibizumab
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.
Sponsors
Juvenile Diabetes Research Foundation
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Deaths Due to Myocardial Infarction | 6 Months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Best Corrected Visual Acuity From Baseline to Month 6 | baseline 6 Months | Mean change in best corrected visual acuity (BCVA) (ETDRS) at 4 meters in the study eye over time through month 6. |
| Mean Change in Retinal Thickness at Month 6 | baseline to6 Months | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 77 |
| 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.
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. | 75 |
| Total | 152 |
Baseline characteristics
| Characteristic | Ranibizumab 0.5mg | Total | Ranibizumab 2.0 mg |
|---|---|---|---|
| Age, Continuous | 64.8 years | 64.1 years | 63.5 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 9 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 19 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 22 Participants | 40 Participants | 18 Participants |
| Race (NIH/OMB) White | 45 Participants | 84 Participants | 39 Participants |
| Region of Enrollment United States | 77 participants | 152 participants | 75 participants |
| Sex: Female, Male Female | 30 Participants | 67 Participants | 37 Participants |
| Sex: Female, Male Male | 47 Participants | 85 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 77 | 0 / 75 |
| serious Total, serious adverse events | 1 / 77 | 3 / 75 |
Outcome results
Primary
Deaths Due to Myocardial Infarction
Time frame: 6 Months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ranibizumab 0.5mg | Deaths Due to Myocardial Infarction | 1 participants |
| Ranibizumab 2.0 mg | Deaths Due to Myocardial Infarction | 3 participants |
Secondary
Mean Change in Best Corrected Visual Acuity From Baseline to Month 6
Mean change in best corrected visual acuity (BCVA) (ETDRS) at 4 meters in the study eye over time through month 6.
Time frame: baseline 6 Months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ranibizumab 0.5mg | Mean Change in Best Corrected Visual Acuity From Baseline to Month 6 | 9.34 letters | Standard Deviation 10.34 |
| Ranibizumab 2.0 mg | Mean Change in Best Corrected Visual Acuity From Baseline to Month 6 | 7.04 letters | Standard Deviation 8.33 |
Secondary
Mean Change in Retinal Thickness at Month 6
Time frame: baseline to6 Months
Population: Data was not collected for 4 participants in the Ranibizumab 0.5mg group for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ranibizumab 0.5mg | Mean Change in Retinal Thickness at Month 6 | 168.57 µm | Standard Deviation 145.67 |
| Ranibizumab 2.0 mg | Mean Change in Retinal Thickness at Month 6 | 159.69 µm | Standard Deviation 124.5 |