Diabetic Macular Edema
Conditions
Brief summary
Anti-inflammatory or anti-angiogenic drugs play an ever- increasing role in the treatment of diabetic macular edema (DME). The drug delivery systems, such as injections of corticosteroid and or vascular endothelial growth factor (VEGF) antibodies into the vitreous cavity or slow release drug capsules surgically implanted in the eyes run the risk of surgical complications including infections, hemorrhages and cataracts and place a huge demand on eye care resources significantly increase the risk of cardiovascular events and death. A non-invasive drug delivery platform with steroid eye drops, reaching the back of the eye to treat DME and other retinal diseases would circumvent most of these problems. A novel drug delivery platform is required for ocular therapy. Oculis ehf. has developed a drug delivery platform, which is based on cyclodextrin nanoparticles that dissolve in the tear fluid to form water-soluble drug/cyclodextrin complex nanoparticles. Animal and initial clinical testing has shown the potential for this technology to increase the drug concentration in the eye tissues including the retina and therefore treat retinal diseases like DME.
Interventions
DRUGDexamethasone nanoparticles eye drops
DexNP 15 mg/mL eye drops 3 times a day (every 8 hours) for 12 weeks
Sponsors
Oculis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Had DME of less than 3 years duration since diagnosis with presence of intraretinal and/or subretinal fluid in the study eye, with CMT of ≥ 310 µm by SD-OCT at baseline (Visit 2) (as measured by the Investigator). 2. Had definite retinal thickening in the study eye due to DME involving the central macula based on the Investigator's clinical evaluation and by SD-OCT; ... Key
Exclusion criteria
1. Had macular edema considered to be due to a cause other than DME; 2. Had a decrease in BCVA due to causes other than DME (e.g., foveal atrophy, pigment abnormalities, dense subfoveal hard exudates, previous vitreoretinal surgery, central serous retinopathy, non-retinal condition, substantial cataract, macular ischemia) that is likely to be decreasing BCVA by 3 lines or more (i.e., cataract would be reducing acuity to 20/40 or worse if eye was otherwise normal). ...
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Early Treatment of Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) | Baseline & Week 12 | The primary efficacy endpoint was summarized by treatment group using descriptive statistics, including 70%, 90% and 95% confidence intervals (CIs). Change from baseline to Week 12 is also summarised by treatment group. The primary analysis of the primary endpoint employed a linear model with change from baseline ETDRS BCVA letters as the response, baseline ETDRS BCVA letters as a covariate, and treatment as a main effect factor, using the ITT population and with multiple imputation pattern mixture model techniques used to impute missing data. |
Countries
Denmark
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DexNP Eye Drop The study eye received 1 DexNP eye drop 3 times a day (every 8 hours) for 12 weeks.
Dexamethasone nanoparticles eye drops: DexNP 15 mg/mL eye drops 3 times a day (every 8 hours) for 12 weeks | 99 |
| Vehicle Eye Drop The study eye received 1 vehicle eye drop 3 times a day (every 8 hours) for 12 weeks.
Dexamethasone nanoparticles eye drops: DexNP 15 mg/mL eye drops 3 times a day (every 8 hours) for 12 weeks | 45 |
| Total | 144 |
Baseline characteristics
| Characteristic | DexNP Eye Drop | Vehicle Eye Drop | Total |
|---|---|---|---|
| Age, Continuous | 63.6 years STANDARD_DEVIATION 9.5 | 66.1 years STANDARD_DEVIATION 9.92 | 64.4 years STANDARD_DEVIATION 9.67 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 98 Participants | 45 Participants | 143 Participants |
| Sex: Female, Male Female | 35 Participants | 17 Participants | 52 Participants |
| Sex: Female, Male Male | 64 Participants | 28 Participants | 92 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 99 | 0 / 45 |
| other Total, other adverse events | 32 / 99 | 9 / 45 |
| serious Total, serious adverse events | 11 / 99 | 1 / 45 |
Outcome results
Primary
Mean Change in Early Treatment of Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA)
The primary efficacy endpoint was summarized by treatment group using descriptive statistics, including 70%, 90% and 95% confidence intervals (CIs). Change from baseline to Week 12 is also summarised by treatment group. The primary analysis of the primary endpoint employed a linear model with change from baseline ETDRS BCVA letters as the response, baseline ETDRS BCVA letters as a covariate, and treatment as a main effect factor, using the ITT population and with multiple imputation pattern mixture model techniques used to impute missing data.
Time frame: Baseline & Week 12
Population: Change from baseline to week 12 in Study Eye ETDRS BCVA Letters using Multiple Imputation (Intent-to-Treat Population)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| DexNP Eye Drop | Mean Change in Early Treatment of Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) | 2.62 ETDRS BCVA Letters |
| Vehicle Eye Drop | Mean Change in Early Treatment of Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) | 1.04 ETDRS BCVA Letters |