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The purpose of this trial is to evaluate the safety and efficacy of suprachoroidal CLS-TA used with intravitreal aflibercept in subjects with DME.
This is a Phase 2, multicenter, randomized, double-masked, controlled, parallel-group study of 6 months duration in treatment-naïve subjects with DME. This study is projected to enroll approximately 60 subjects, randomly assigned 1:1 to one of two treatment groups.
The study design includes up to 8 clinic visits over approximately 24 weeks. Subjects will attend visits for Screening (Visit 1, Days -30 to 0); Randomization and Baseline (Visit 2, Day 0 before dosing); Dosing and Evaluation (Visit 2 after dosing to Visit 5, Day 0 through Week 12); As-needed (PRN) Dosing and Follow up (Visit 6 through Visit 7, Week 16 through Week 20), and End of Study (Visit 8, Week 24).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active | Active Comparator | Treatment will consist of IVT injection of Aflibercept followed by an SC injection of CLS-TA |
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| Control | Sham Comparator | Treatment will consist of IVT aflibercept injection followed by a sham SC procedure |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IVT aflibercept | Drug | IVT aflibercept [2 mg/0.05 mL] |
|
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change From Baseline in Best Corrected Visual Acuity Letter Score | 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 in the number of letters read correctly on an ETDRS eye chart. An increase from the pre-treatment state in BCVA of 15 letters or more represents a clinically meaningful improvement. | Baseline, 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change From Baseline 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Thomas Ciulla, MD | Clearside Biomedical | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Retinal Consultants of Arizona and Retinal Research Institute | Phoenix | Arizona | 85014-2709 | United States | ||
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| ID | Title | Description |
|---|---|---|
| FG000 | Active | Treatment will consist of IVT injection of Aflibercept followed by an SC injection of CLS-TA IVT aflibercept: IVT aflibercept [2 mg (0.05 mL)] SC CLS-TA: SC CLS-TA [40 mg/mL] |
| FG001 | Control |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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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 | Jan 19, 2018 |
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| Sham SC | Drug | sham SC |
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| SC CLS-TA | Drug | CLS-TA [4 mg/100 μL] SC injection |
|
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| Baseline, 6 months |
| Retina Centers, PC |
| Tucson |
| Arizona |
| 85704 |
| United States |
| California Retina Consultants | Bakersfield | California | 93309 | United States |
| Retina Vitreous Medical Group Clinical Research | Beverly Hills | California | 90211-1841 | United States |
| Northern California Retina Vitreous Associates Medical Group, Inc. | Mountain View | California | 94040 | United States |
| Retina Institute of California | Palm Desert | California | 92260 | United States |
| Retina Consultants San Diego | Poway | California | 92064-2526 | United States |
| MedEye Associates | Miami | Florida | 33143-5188 | United States |
| Retina Specialty Institute | Pensacola | Florida | 32503 | United States |
| Sarasota Retina Institute | Sarasota | Florida | 34239 | United States |
| Center for Retina and Macular Disease | Winter Haven | Florida | 33880 | United States |
| Emory Eye Center | Augusta | Georgia | 30909-6440 | United States |
| Marietta Eye Clinic | Marietta | Georgia | 30060 | United States |
| Midwest Eye Institute | Indianapolis | Indiana | 46290 | United States |
| Retina and Vitrous Associates of Kentucky | Lexington | Kentucky | 40509 | United States |
| The Johns Hopkins Wilmer Eye Institute | Baltimore | Maryland | 21287 | United States |
| Cumberland Valley Retina Consultants | Hagerstown | Maryland | 21740-5940 | United States |
| Retina Associates of NJ | Teaneck | New Jersey | 07666 | United States |
| Western Carolina Retinal Associates | Asheville | North Carolina | 28803 | United States |
| Oregon Retina Institute | Medford | Oregon | 97504 | United States |
| Black Hills Regional Eye Institute | Rapid City | South Dakota | 57701-7374 | United States |
| Retina Research Institute of Texas | Abilene | Texas | 79606-1224 | United States |
| Texas Retina Associates-Arlington | Arlington | Texas | 76012-2505 | United States |
| Austin Retina Associates | Austin | Texas | 78705 | United States |
| Texas Retina Associates | Dallas | Texas | 75231 | United States |
| Valley Retina Institute, P.A. | McAllen | Texas | 78503 | United States |
| Valley Retina Institute | McAllen | Texas | 78503 | United States |
| Medical Center Ophthalmology Associates | San Antonio | Texas | 78240-1502 | United States |
| Retina Consultants of Houston | The Woodlands | Texas | 77384 | United States |
Treatment will consist of IVT aflibercept injection followed by a sham SC procedure
IVT aflibercept: IVT aflibercept [2 mg (0.05 mL)]
Sham SC: sham SC
| COMPLETED |
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| NOT COMPLETED |
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The Safety population included all randomly assigned subjects who were administered at least 1 dose of the study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Active | Treatment will consist of IVT injection of Aflibercept followed by an SC injection of CLS-TA IVT aflibercept: IVT aflibercept [2 mg (0.05 mL)] SC CLS-TA: SC CLS-TA [40 mg/mL] |
| BG001 | Control | Treatment will consist of IVT aflibercept injection followed by a sham SC procedure IVT aflibercept: IVT aflibercept [2 mg (0.05 mL)] Sham SC: sham SC |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||
| Age, Continuous | Age of subject, in years, relative to the date of the Screening Visit. | Mean | Standard Deviation | years |
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| Sex: Female, Male | Biological gender of the subject. | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Ethnic background as reported by the subject. | Count of Participants | Participants |
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| Race (NIH/OMB) | Race as reported by the subject. | Count of Participants | Participants |
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| Region of Enrollment | Region of participation by the subject. | Number | participants |
| |||||||||||||||||
| Best corrected visual acuity | Best corrected visual acuity letter score following refraction and Early Treatment Diabetic Retinopathy Study protocol. | Mean | Standard Deviation | letters |
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| 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 | Mean Change From Baseline in Best Corrected Visual Acuity Letter Score | 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 in the number of letters read correctly on an ETDRS eye chart. An increase from the pre-treatment state in BCVA of 15 letters or more represents a clinically meaningful improvement. | The Intent-to-treat population included all randomized subjects who received at least 1 study treatment | Posted | Least Squares Mean | Standard Error | letters | Baseline, 6 months |
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| Secondary | Mean Change From Baseline 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 randomized subjects who received at least 1 study treatment | Posted | Least Squares Mean | Standard Error | microns | Baseline, 6 months |
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Adverse events were collected over 24 weeks of follow-up.
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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 | Active | Treatment will consist of IVT injection of Aflibercept followed by an SC injection of CLS-TA IVT aflibercept: IVT aflibercept [2 mg (0.05 mL)] SC CLS-TA: SC CLS-TA [40 mg/mL] | 2 | 36 | 6 | 36 | 10 | 36 |
| EG001 | Control | Treatment will consist of IVT aflibercept injection followed by a sham SC procedure IVT aflibercept: IVT aflibercept [2 mg (0.05 mL)] Sham SC: sham SC | 0 | 35 | 4 | 35 | 11 | 35 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Acute left ventricular failure | Cardiac disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Acute myocardial infarction | Cardiac disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Cardiac arrest | Cardiac disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Hepatorenal syndrome | Hepatobiliary disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Osteomyelitis | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
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| Pneumonia staphylococcal | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
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| Femur fracture | Injury, poisoning and procedural complications | MedDRA (19.0) | Non-systematic Assessment |
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| Hip fracture | Injury, poisoning and procedural complications | MedDRA (19.0) | Non-systematic Assessment |
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| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Chronic kidney disease | Renal and urinary disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Diabetic neuropathic ulcer | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Orthostatic hypotension | Vascular disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anxiety | Psychiatric disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Conjunctival haemorrhage | Eye disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Eye pain | Eye disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Intraocular pressure increased | Eye disorders | MedDRA (19.0) | Non-systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
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| Retinal exudates | Eye disorders | MedDRA (19.0) | Non-systematic Assessment |
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The institutions and Investigators participating in this study shall have no right to publish or present the results of this study without the prior written consent of Clearside Biomedical, Inc.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Thomas Ciulla, MD MBA | Clearside Biomedical, Inc. | (678) 392-2318 | thomas.ciulla@clearsidebio.com |
| Mar 2, 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 |
| D012164 | Retinal Diseases |
| D005128 | Eye Diseases |
| D003925 | Diabetic Angiopathies |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D048909 | Diabetes Complications |
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| ID | Term |
|---|---|
| C533178 | aflibercept |
| D014222 | Triamcinolone Acetonide |
| ID | Term |
|---|---|
| D014221 | Triamcinolone |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |
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| >=65 years |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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Estimated Value calculated as Active minus Control. |
| Superiority |
The sample size was determined such that the difference in visual acuity between the ACTIVE treatment group and CONTROL treatment group could be estimated within +/- five ETDRS letters. Week 24 data from the Eylea prescribing information was used to estimate a pooled standard deviation of 9.17 letters. With 28 subjects per arm, a two-sided 90% confidence interval with a distance from the mean difference to the limits (half of interval width) will be less than 5 letters. |
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