Diabetic Macular Edema
Conditions
Keywords
Diabetes mellitus, Diabetic retinopathy, Microneedle, Microinjection, Triamcinolone, Choroid, Choroid Injection, Aflibercept, Suprachoroidal, Triamcinolone acetonide
Brief summary
This study is designed to demonstrate the safety and tolerability of suprachoroidal CLS-TA alone or in combination with intravitreal aflibercept in subjects with diabetic macular edema associated with diabetes mellitus.
Detailed description
This is a Phase 1/2, multicenter, open-label study in subject with DME associated with diabetes mellitus. Subjects will be screened and if eligible, will be assigned to study arm at the Baseline Visit (Visit 1, Day 0). Following the Baseline Visit, subjects will participate in six monthly follow-up visits (Visit 2-7; Weeks 4-24) for safety and efficacy assessments and to determine whether additional therapy is needed based upon pre-defined criteria.
Interventions
DRUGIVT Aflibercept
IVT aflibercept \[2 mg (50 µL)\]
DRUGSC CLS-TA
\[4 mg (100 µL)\]
Sponsors
Clearside Biomedical, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men or women ≥ 18 years of age with type 1 or type 2 diabetes mellitus * DME with central involvement (\>320 microns in the central subfield on SD-OCT) in the study eye * ETDRS BCVA letter score of 83 to 14, inclusive (Snellen equivalent of 20/25 to 20/500) in the study eye
Exclusion criteria
* Evidence of DME due to any other cause other than diabetes mellitus in the study eye * PRP or focal laser photocoagulation in the study eye within 90 days of screening * Intraocular pressure ≥ 22 mmHg or uncontrolled glaucoma (open angle or angle closure) in the study eye * History of any previous ophthalmic surgeries in the study eye within 90 days of screening * High risk PDR in the study eye, for whom enrollment into the study, in the principal investigator's opinion would put the eye at undue risk for vision loss * Any previous treatment in the study eye with ILUVIEN implant * Previous treatment for DME in the study eye (TX naive arm only); treatment in the study eye for DME greater than 1 year prior to screening can be considered as treatment naive, at the investigator's discretion * Subjects previously treated for DME cannot have been treated in the study eye with an intravitreal injection of anti-VEGF or periocular corticosteroids within 90 days prior to screening (Previous TX arm only) * Subjects previously treated for DME cannot have been treated in the study eye with intraocular corticosteroids within 6 months prior to screening (Previous TX arm only)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events | Over 6 months of follow-up | Number of participants with treatment emergent adverse events and serious adverse events reported over 6 months of follow-up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Intraocular Pressure | Baseline and 6 months | Baseline and change from baseline at 6 months in intraocular pressure as measured by applanation tonometry |
| Mean Change From Baseline in Central Subfield Thickness | Baseline and 6 months | Baseline and change from baseline at 6 months in central subfield thickness. Central subfield thickness (CST) is a diagnostic measurement used in identifying the presence of edema in the circular area 1 mm in diameter centered around the fovea. CST was measured using spectral domain optical coherence tomography (SD-OCT). A masked reading center graded the SD-OCT digital images. A negative change from baseline value represents a reduction in macular edema. |
| Best Corrected Visual Acuity | Baseline and 6 months | Baseline and Change from baseline at 6 months in best corrected visual acuity before and after treatment Best corrected visual acuity (BCVA) refers to the measurement of the best possible vision that can be achieved following refraction or correction. BCVA was assessed following the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol and was measured as the number of letters read correctly on an ETDRS eye chart. A positive change from baseline value represents an improvement in vision. |
| CLS-TA Injections | 2 to 6 months following initial treatment with study drug | After the initial treatment with CLS-TA, with or without intravitreal aflibercept, at Baseline, retreatment with CLS-TA was allowed in either treatment group from Month 2 through Month 6 if pre-defined retreatment criteria were met. Number of patients receiving 0, 1, 2, 3, 4 or 5 retreatments with CLS-TA. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TX Naïve Arm Treatment in the TX Naive arm will consist of one unilateral injection of IVT aflibercept in combination with one unilateral injection of SC CLS-TA in the same eye.
IVT Aflibercept: IVT aflibercept \[2 mg (50 µL)\]
SC CLS-TA: \[4 mg (100 µL)\] | 10 |
| Previous TX Arm Treatment in the Previous TX arm of the study will consist of one unilateral injection of SC CLS-TA.
SC CLS-TA: \[4 mg (100 µL)\] | 10 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | TX Naïve Arm | Previous TX Arm | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 4 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 6 Participants | 11 Participants |
| Age, Continuous | 61.9 Years STANDARD_DEVIATION 7.28 | 63.1 Years STANDARD_DEVIATION 8.31 | 62.5 Years STANDARD_DEVIATION 7.63 |
| Baseline Best Corrected Visual Acuity | 67.2 Letters STANDARD_DEVIATION 11.66 | 67.2 Letters STANDARD_DEVIATION 8.95 | 67.2 Letters STANDARD_DEVIATION 10.12 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 4 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 | 6 Participants | 6 Participants | 12 Participants |
| Region of Enrollment United States | 10 participants | 10 participants | 20 participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 8 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 8 / 10 | 9 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events
Number of participants with treatment emergent adverse events and serious adverse events reported over 6 months of follow-up
Time frame: Over 6 months of follow-up
Population: The Safety population included all subjects who received study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TX Naïve Arm | Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events | Number of participants with treatment emergent adverse events | 8 Participants |
| TX Naïve Arm | Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events | Number of participants with serious adverse events | 0 Participants |
| Previous TX Arm | Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events | Number of participants with serious adverse events | 0 Participants |
| Previous TX Arm | Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events | Number of participants with treatment emergent adverse events | 9 Participants |
Secondary
Best Corrected Visual Acuity
Baseline and Change from baseline at 6 months in best corrected visual acuity before and after treatment Best corrected visual acuity (BCVA) refers to the measurement of the best possible vision that can be achieved following refraction or correction. BCVA was assessed following the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol and was measured as the number of letters read correctly on an ETDRS eye chart. A positive change from baseline value represents an improvement in vision.
Time frame: Baseline and 6 months
Population: The Intent-to-treat population included all subjects who received study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TX Naïve Arm | Best Corrected Visual Acuity | Baseline | 67.2 Letters | Standard Deviation 11.66 |
| TX Naïve Arm | Best Corrected Visual Acuity | Month 6 | 8.5 Letters | Standard Deviation 11.96 |
| Previous TX Arm | Best Corrected Visual Acuity | Baseline | 67.2 Letters | Standard Deviation 8.95 |
| Previous TX Arm | Best Corrected Visual Acuity | Month 6 | 1.1 Letters | Standard Deviation 11.94 |
Secondary
CLS-TA Injections
After the initial treatment with CLS-TA, with or without intravitreal aflibercept, at Baseline, retreatment with CLS-TA was allowed in either treatment group from Month 2 through Month 6 if pre-defined retreatment criteria were met. Number of patients receiving 0, 1, 2, 3, 4 or 5 retreatments with CLS-TA.
Time frame: 2 to 6 months following initial treatment with study drug
Population: The Intent-to-treat population included all subjects who received study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TX Naïve Arm | CLS-TA Injections | 4 additional injections | 2 Participants |
| TX Naïve Arm | CLS-TA Injections | 0 additional injections | 4 Participants |
| TX Naïve Arm | CLS-TA Injections | 1 additional injection | 2 Participants |
| TX Naïve Arm | CLS-TA Injections | 2 additional injections | 0 Participants |
| TX Naïve Arm | CLS-TA Injections | 3 additional injections | 2 Participants |
| Previous TX Arm | CLS-TA Injections | 3 additional injections | 0 Participants |
| Previous TX Arm | CLS-TA Injections | 2 additional injections | 2 Participants |
| Previous TX Arm | CLS-TA Injections | 0 additional injections | 1 Participants |
| Previous TX Arm | CLS-TA Injections | 4 additional injections | 4 Participants |
| Previous TX Arm | CLS-TA Injections | 1 additional injection | 3 Participants |
Secondary
Mean Change From Baseline in Central Subfield Thickness
Baseline and change from baseline at 6 months in central subfield thickness. Central subfield thickness (CST) is a diagnostic measurement used in identifying the presence of edema in the circular area 1 mm in diameter centered around the fovea. CST was measured using spectral domain optical coherence tomography (SD-OCT). A masked reading center graded the SD-OCT digital images. A negative change from baseline value represents a reduction in macular edema.
Time frame: Baseline and 6 months
Population: The Intent-to-treat population included all subjects who received study treatment. No values were imputed for missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TX Naïve Arm | Mean Change From Baseline in Central Subfield Thickness | Baseline | 421.6 Microns | Standard Deviation 94.33 |
| TX Naïve Arm | Mean Change From Baseline in Central Subfield Thickness | Month 6 | -90.9 Microns | Standard Deviation 62.48 |
| Previous TX Arm | Mean Change From Baseline in Central Subfield Thickness | Baseline | 472.7 Microns | Standard Deviation 109.46 |
| Previous TX Arm | Mean Change From Baseline in Central Subfield Thickness | Month 6 | -119.6 Microns | Standard Deviation 65.48 |
Secondary
Mean Change From Baseline in Intraocular Pressure
Baseline and change from baseline at 6 months in intraocular pressure as measured by applanation tonometry
Time frame: Baseline and 6 months
Population: The Intent-to-treat population included all subjects who received study treatment. No values were imputed for missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TX Naïve Arm | Mean Change From Baseline in Intraocular Pressure | Baseline | 14.2 mm Hg | Standard Deviation 3.52 |
| TX Naïve Arm | Mean Change From Baseline in Intraocular Pressure | Month 6 | -0.3 mm Hg | Standard Deviation 2.41 |
| Previous TX Arm | Mean Change From Baseline in Intraocular Pressure | Baseline | 13.3 mm Hg | Standard Deviation 2.5 |
| Previous TX Arm | Mean Change From Baseline in Intraocular Pressure | Month 6 | 2.8 mm Hg | Standard Deviation 7.89 |