Diabetic Macular Edema
Conditions
Keywords
Diabetes, Macula, Edema, Retina
Brief summary
This is an open-label, Phase I/II study of intravitreally administered ranibizumab either 0.5-mg and/or 2.0-mg in subjects with clinical, angiographic, and ocular coherence tomography (OCT) evidence of diabetic retinopathy with associated diabetic macular edema following bevacizumab therapy. Thirty patients will be enrolled in this study. Consented, enrolled subjects will receive multiple open-label intravitreal injections of 0.5 mg ranibizumab administered every 30 days (±7 days) for 3 injections during the mandatory treatment phase (Day 0, Month 1, and Month 2). Subjects with complete resolution of diabetic macular edema after 3 intravitreal injections of 0.5 mg ranibizumab will be treated as necessary with 0.5 mg ranibizumab to treat recurrent macular edema for an additional 9 months (12 months from Day 0). The intent is to administer additional ranibizumab treatment if there is evidence of disease activity documented on OCT (e.g., intra-retinal fluid, subretinal fluid and/or cystic changes). Subjects with residual diabetic macular edema following 3 intravitreal injections of 0.5 mg ranibizumab will be receive 3 intravitreal injections of 2.0 mg ranibizumab administered every 30 days (±7 days) for 3 injections at the Month 3, Month 4, and Month 5 study visits. Beginning at the Month 6 study visit, subjects with complete resolution of diabetic macular edema following 3 intravitreal injections of 2.0 mg ranibizumab will treated as necessary with 2.0 mg ranibizumab injections only to treat recurrent macular edema for an additional 6 months (12 months from Day 0). Subjects with residual diabetic macular edema following 3 consecutive intravitreal injections of 2.0 mg ranibizumab will be treated as necessary with 2.0 mg ranibizumab to treat persistent or recurrent macular edema for an additional 6 months (12 months from Day 0). Focal photocoagulation or intravitreal triamcinolone may be administered at the physician's discretion as an adjunct to ranibizumab injections beginning at Month 6 through Month 12 of the study. All subjects will make monthly visits for 12 months for evaluation of safety and efficacy. All subjects will have their first injection of ranibizumab on Day 0 and undergo a safety visit one week (±2 days) after the first injection. At subsequent visits, the subject will have a safety evaluation at the monthly scheduled follow-up visit prior to any intravitreal injection. Subjects will be contacted by the site personnel 1-2 days after each injection to elicit reports of decreased vision or pain or unusual new ocular symptoms in the study eye.
Interventions
DRUGRanibizumab
0.05ml of 0.5mg or 2.0mg ranibizumab injected intravitreally
Sponsors
Genentech, Inc.
California Retina Consultants
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ability to provide written informed consent and comply with study assessments for the full duration of the study * Age \> 18 years * Diagnosis of diabetes mellitus (type 1 or 2)Any one of the following will be considered to be sufficient evidence that diabetes is present:Current regular use of insulin for treatment of diabetes or current regular use of oral anti-hyperglycemia agent for the treatment of diabetes * Clinical evidence of retinal thickening due to macular edema involving the center of the macula, associated with diabetic retinopathy. * Previous history of two consecutive intravitreal bevacizumab injections for the treatment of diabetic macular edema with documented incomplete resolution of central subfield thickening by OCT (consecutive injections administered \< 7 weeks apart and within the past 12 months). * Central diabetic macular edema present on clinical examination and OCT testing with central 1mm subfield thickness greater than 300 microns as measured on SD-OCT. * Visual acuity score greater than or equal to 19 letters (20/400) and less than or equal to 73 letters (20/40) by the ETDRS visual acuity protocol. * Media clarity, pupillary dilation and patient cooperation sufficient to allow OCT testing and retinal photography
Exclusion criteria
* Pregnancy (positive pregnancy test) or known to be pregnant; also pre-menopausal women not using adequate contraception. * Participation in another ocular investigation or trial simultaneously * Blood pressure \> 180/110 (systolic above 180 OR diastolic above 110) * Any condition that, in the opinion of the investigator, would preclude participation in the study (e.g. chronic alcoholism, drug abuse) * Evidence of vitreoretinal interface abnormality after ocular exam or OCT that may be contributing to the macular edema * 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 or geographic atrophy) * 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-Gas) * Evidence of neovascularization of the iris or retina * Evidence of central atrophy or fibrosis in the study eye * Presence of substantial cataract, one that might decrease the vision by 3 or more lines of vision at sometime during the study. * History of vitreous surgery in the study eye * History of cataract surgery within 6 months of enrollment. * History of YAG capsulotomy within 2 months of enrollment. * Visual acuity \<20/400 in the fellow eye * Uncontrolled glaucoma (pressure \>30) despite treatment with glaucoma medications. * History of cerebral vascular accident or myocardial infarction within 3 months prior to Day 0.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Mean Change in Visual Acuity Scores at Month 6 Compared to Baseline | baseline and 6 months | To determine the mean change in the best-corrected visual acuity on an ETDRS visual acuity chart at a starting distance of 4 meters from baseline to 6 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in 1-mm Central Subfield (CST) Thickness as Measured by OCT at Month 6 Compared to Baseline | baseline and 6 months | To determine the mean change in central 1-mm subfield thickness as measured by spectral-domain OCT from baseline to 6 months . |
| Qualitative Assessment of Diabetic Macular Edema (DME) | Baeline and 6 months | To compare the percentage of subjects with compete or partial/no resolution of diabetic macular edema in response to the ranibizumab 0.5 and 2.0 mg doses. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 2.0 mg Ranibizumab Subjects who presented with persistent DME at month 3 following 3 months of monthly 0.5 mg ranibizumab injections received 3 monthly injections of 2.0 mg Ranibizumab. | 43 |
| Total | 43 |
Baseline characteristics
| Characteristic | 2.0 mg Ranibizumab |
|---|---|
| Age, Continuous | 64.0 years STANDARD_DEVIATION 10.1 |
| Region of Enrollment United States | 43 participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 43 |
| serious Total, serious adverse events | 1 / 43 |
Outcome results
Primary
Overall Mean Change in Visual Acuity Scores at Month 6 Compared to Baseline
To determine the mean change in the best-corrected visual acuity on an ETDRS visual acuity chart at a starting distance of 4 meters from baseline to 6 months.
Time frame: baseline and 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.5mg and 2.0mgRanibizumab | Overall Mean Change in Visual Acuity Scores at Month 6 Compared to Baseline | Baseline | 58.8 letters | Standard Deviation 9.7 |
| 0.5mg and 2.0mgRanibizumab | Overall Mean Change in Visual Acuity Scores at Month 6 Compared to Baseline | 6 months | 67.6 letters | Standard Deviation 9.3 |
| 0.5mg and 2.0mgRanibizumab | Overall Mean Change in Visual Acuity Scores at Month 6 Compared to Baseline | Change from Baseline to 6 months | 8.8 letters | Standard Deviation 9.3 |
Secondary
Mean Change in 1-mm Central Subfield (CST) Thickness as Measured by OCT at Month 6 Compared to Baseline
To determine the mean change in central 1-mm subfield thickness as measured by spectral-domain OCT from baseline to 6 months .
Time frame: baseline and 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.5mg and 2.0mgRanibizumab | Mean Change in 1-mm Central Subfield (CST) Thickness as Measured by OCT at Month 6 Compared to Baseline | Baseline | 500.6 microns | Standard Deviation 129.1 |
| 0.5mg and 2.0mgRanibizumab | Mean Change in 1-mm Central Subfield (CST) Thickness as Measured by OCT at Month 6 Compared to Baseline | 6 months | 335.2 microns | Standard Deviation 91.5 |
| 0.5mg and 2.0mgRanibizumab | Mean Change in 1-mm Central Subfield (CST) Thickness as Measured by OCT at Month 6 Compared to Baseline | Change from Baseline to 6 months | -165.4 microns | Standard Deviation 91.5 |
Secondary
Qualitative Assessment of Diabetic Macular Edema (DME)
To compare the percentage of subjects with compete or partial/no resolution of diabetic macular edema in response to the ranibizumab 0.5 and 2.0 mg doses.
Time frame: Baeline and 6 months
Population: At 6 months, 18 out of the 43 subjects (42%) showed complete resolution of DME. 25 out of the 43 subjects (58%) showed partial or no resolution of DME at 6 months.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 0.5mg and 2.0mgRanibizumab | Qualitative Assessment of Diabetic Macular Edema (DME) | complete resolution | 42 percentage of participants |
| 0.5mg and 2.0mgRanibizumab | Qualitative Assessment of Diabetic Macular Edema (DME) | partial/no resolution | 58 percentage of participants |