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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TX Naïve Arm | Experimental | 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. |
|
| Previous TX Arm | Experimental | Treatment in the Previous TX arm of the study will consist of one unilateral injection of SC CLS-TA. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IVT Aflibercept | Drug | IVT aflibercept [2 mg (50 µL)] |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Over 6 months of follow-up |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change From Baseline in Intraocular Pressure | Baseline and change from baseline at 6 months in intraocular pressure as measured by applanation tonometry | Baseline and 6 months |
| Mean Change From Baseline in Central Subfield Thickness |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Thomas Ciulla, MD MBA | Clearside Biomedical, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Retina Vitreous Associates Medical Group Inc | Mountain View | California | 94040 | United States | ||
| Retina Consultants of Houston, PA |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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)] |
| FG001 | 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)] |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The Intent-to-treat population included all subjects who received study treatment.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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)] |
| BG001 | Previous TX Arm |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | The Safety population included all subjects who received study treatment. | Posted | Count of Participants | Participants | Over 6 months of follow-up |
|
6 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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)] |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cataract | Eye disorders | MedDRA 20.0 | Non-systematic Assessment | #Study eye |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Thomas Ciulla, MD MBA | Clearside Biomedical, Inc. | (678) 392-2318 | thomas.ciulla@clearsidebio.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 23, 2017 | Mar 1, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D003930 | Diabetic Retinopathy |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| C533178 | aflibercept |
| D014222 | Triamcinolone Acetonide |
| ID | Term |
|---|---|
| D014221 | Triamcinolone |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 |
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| SC CLS-TA | Drug | [4 mg (100 µL)] |
|
|
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.
| Baseline and 6 months |
| 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. | Baseline and 6 months |
| 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. | 2 to 6 months following initial treatment with study drug |
| The Woodlands |
| Texas |
| 77384 |
| United States |
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)] |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Age of patients in years relative to the date of the Screening visit. | Mean | Standard Deviation | Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Baseline Best Corrected Visual Acuity | 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. | Mean | Standard Deviation | Letters |
|
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)]
|
|
| Secondary | Mean Change From Baseline in Intraocular Pressure | Baseline and change from baseline at 6 months in intraocular pressure as measured by applanation tonometry | The Intent-to-treat population included all subjects who received study treatment. No values were imputed for missing data. | Posted | Mean | Standard Deviation | mm Hg | Baseline and 6 months |
|
|
|
| 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. | The Intent-to-treat population included all subjects who received study treatment. No values were imputed for missing data. | Posted | Mean | Standard Deviation | Microns | Baseline and 6 months |
|
|
|
| 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. | The Intent-to-treat population included all subjects who received study treatment. | Posted | Mean | Standard Deviation | Letters | Baseline and 6 months |
|
|
|
| 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. | The Intent-to-treat population included all subjects who received study treatment. | Posted | Count of Participants | Participants | 2 to 6 months following initial treatment with study drug |
|
|
|
| 0 |
| 10 |
| 0 |
| 10 |
| 8 |
| 10 |
| EG001 | 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)] | 0 | 10 | 0 | 10 | 9 | 10 |
| Cataract | Eye disorders | MedDRA 20.0 | Non-systematic Assessment | #Fellow eye |
|
| Conjunctival haemorrhage | Eye disorders | MedDRA 20.0 | Non-systematic Assessment | #Study eye |
|
| Dry eye | Eye disorders | MedDRA 20.0 | Non-systematic Assessment | #Study eye |
|
| Dry eye | Eye disorders | MedDRA 20.0 | Non-systematic Assessment | #Fellow eye |
|
| Episcleritis | Eye disorders | MedDRA 20.0 | Non-systematic Assessment | #Fellow eye |
|
| Eye irritation | Eye disorders | MedDRA 20.0 | Non-systematic Assessment | #Study eye |
|
| Eye irritation | Eye disorders | MedDRA 20.0 | Non-systematic Assessment | #Fellow eye |
|
| Eye pain | Eye disorders | MedDRA 20.0 | Non-systematic Assessment | #Study eye |
|
| Iritis | Eye disorders | MedDRA 20.0 | Non-systematic Assessment | #Study eye |
|
| Macular fibrosis | Eye disorders | MedDRA 20.0 | Non-systematic Assessment | #Study eye |
|
| Ocular hypertension | Eye disorders | MedDRA 20.0 | Non-systematic Assessment | #Study eye |
|
| Nasopharyngitis | Infections and infestations | MedDRA 20.0 | Non-systematic Assessment |
|
| Intraocular pressure increased | Investigations | MedDRA 20.0 | Non-systematic Assessment | #Study eye |
|
| Optic nerve cup/disc ratio increased | Investigations | MedDRA 20.0 | Non-systematic Assessment | #Fellow eye |
|
| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA 20.0 | Non-systematic Assessment |
|
| Type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDRA 20.0 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 20.0 | Non-systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA 20.0 | Non-systematic Assessment |
|
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 20.0 | Non-systematic Assessment |
|
The institution and investigators participating in this trial shall have no right to publish or present the results of this study without the prior written consent of Clearside Biomedical.
| D012164 | Retinal Diseases |
| D005128 | Eye Diseases |
| D003925 | Diabetic Angiopathies |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D048909 | Diabetes Complications |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |
| Month 6 |
|
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| Month 6 |
|
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| Month 6 |
|
|
| 2 additional injections |
|
| 3 additional injections |
|
| 4 additional injections |
|