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The study is designed to evaluate the safety and efficacy of suprachoroidally administered triamcinolone acetonide, CLS-TA, in subjects with macular edema associated with non-infectious uveitis.
This is a Phase 3, randomized, masked, sham-controlled, multicenter study to assess the safety and efficacy of 4 mg of CLS-TA administered via suprachoroidal injection compared to a sham injection procedure in the treatment of subjects with macular edema associated with non-infectious uveitis.
Qualified subjects will be randomized to receive two suprachoroidal injections of CLS-TA administered to the study eye or two sham injection procedures administered to the study eye approximately 12 weeks apart (Visit 2 and Visit 5). Follow-up visits will be conducted monthly up to 24 weeks (Visit 8).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 4mg CLS-TA Suprachoriodal Injection | Experimental | Suprachoroidal injection of 40 mg/mL (4 mg in 100 µL) of CLS-TA |
|
| Sham Procedure | Sham Comparator | Matching suprachoroidal syringe with sham procedure |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 4mg CLS-TA Suprachoriodal Injection | Drug | CLS-TA, 40 mg/mL (4 mg in 100 µL), administered as a single injection at 2 timepoints |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects Demonstrating ≥ 15 Letter Improvement From Baseline in Best Corrected Visual Acuity at 24 Weeks | 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 electronic Visual Acuity (eVA). An increase from the pre-treatment state in BCVA of 15 letters or more represents a clinically meaningful improvement. | Baseline, 24 weeks |
| 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. Only images that were gradable by the central reading center were included in the analysis. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Thomas Cuilla, MD, MBA | Clearside Biomedical, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Retinal Consultants of Arizona | Phoenix | Arizona | 85014 | United States | ||
| Retina Centers, PC |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36787524 | Derived | Yeh S, Ciulla T. Suprachoroidal triamcinolone acetonide injectable suspension for macular edema associated with noninfectious uveitis: an in-depth look at efficacy and safety. Am J Manag Care. 2023 Feb;29(2 Suppl):S19-S28. doi: 10.37765/ajmc.2023.89324. | |
| 36399237 | Derived | Yeh S, Henry CR, Kapik B, Ciulla TA. Triamcinolone Acetonide Suprachoroidal Injectable Suspension for Uveitic Macular Edema: Integrated Analysis of Two Phase 3 Studies. Ophthalmol Ther. 2023 Feb;12(1):577-591. doi: 10.1007/s40123-022-00603-x. Epub 2022 Nov 18. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 4mg CLS-TA Suprachoriodal Injection | Suprachoroidal injection of 40 mg/mL (4 mg in 100 µL) of CLS-TA 4mg CLS-TA Suprachoriodal Injection: CLS-TA, 40 mg/mL (4 mg in 100 µL), administered as a single injection at 2 timepoints |
| FG001 | Sham Procedure |
| 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 | Apr 12, 2017 |
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|
| Sham Procedure | Drug | Sham procedure administered at 2 timepoints |
|
|
| Baseline, 24 weeks |
| Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Number of subjects with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) reported between the first dose of study drug and study exit. | Baseline to 24 weeks |
| Tucson |
| Arizona |
| 85704 |
| United States |
| California Retina Consultants | Bakersfield | California | 93309 | United States |
| Retina-Vitreous Associates Medical Group | Beverly Hills | California | 90211 | United States |
| USC Eye Institute | Los Angeles | California | 90033 | United States |
| Northern California Retina Vitreous Associates Medical Group, Inc. | Mountain View | California | 94040 | United States |
| Orange County Retina Medical Group | Santa Ana | California | 92705 | United States |
| University of Colorado | Aurora | Colorado | 80045 | United States |
| Colorado Retina Associates | Golden | Colorado | 80401 | United States |
| Retina Group of Florida | Fort Lauderdale | Florida | 33308 | United States |
| Center for Retina and Macular Disease | Lakeland | Florida | 33805 | United States |
| Emory Eye Center Emory University | Atlanta | Georgia | 30322 | United States |
| Marietta Eye Clinic | Marietta | Georgia | 30060 | United States |
| Northwestern University | Chicago | Illinois | 60611 | United States |
| University of Illinois at Chicago | Chicago | Illinois | 60612 | United States |
| Illinois Retina Associates, S.C. | Oak Park | Illinois | 60304 | United States |
| Midwest Eye Retina Practicing at Midwest Eye Institute | Indianapolis | Indiana | 46290 | United States |
| Elman Retina Group, PA | Baltimore | Maryland | 21237 | United States |
| The Retina Group of Washington | Chevy Chase | Maryland | 20815 | United States |
| Valley Eye Physicians and Surgeons, PC | Ayer | Massachusetts | 01432 | United States |
| Ophthalmic Consultants of Boston | Boston | Massachusetts | 02114 | United States |
| Ocular Immunology and Uveitis Foundation; Massachusetts Eye Research and Surgery Institution | Waltham | Massachusetts | 01741 | United States |
| Discover Vision Centers | Independence | Missouri | 64055 | United States |
| Metropolitan Eye Research & Surgery Institute | Palisades Park | New Jersey | 07650 | United States |
| Weill Cornell Medical College | New York | New York | 10021 | United States |
| Retina Consultants PLLC | Slingerlands | New York | 12159 | United States |
| Charlotte Eye Ear Nose and Throat Associates, PA | Belmont | North Carolina | 28012 | United States |
| Wake Forest Baptist Health Eye Center | Winston-Salem | North Carolina | 27103 | United States |
| Bergstrom Eye Research | Fargo | North Dakota | 58103 | United States |
| Oregon Health & Science University Casey Eye Institute | Portland | Oregon | 97239 | United States |
| Mid Atlantic Retina | Philadelphia | Pennsylvania | 19107 | United States |
| University of Pittsburgh Medical Center Eye Center | Pittsburgh | Pennsylvania | 15213 | United States |
| Innovative Clinical Research | Greenville | South Carolina | 29605 | United States |
| Austin Retina Associates | Austin | Texas | 78705 | United States |
| Texas Retina Associates | Dallas | Texas | 75231 | United States |
| Retina Consultants of Houston | Houston | Texas | 77030 | United States |
| Foresight Studies, LLC | San Antonio | Texas | 78233 | United States |
| Retina Consultants of Houston | The Woodlands | Texas | 77384 | United States |
| Virginia Eye Consultants | Norfolk | Virginia | 23502 | United States |
| Vitreoretinal Associates of Washington | Bellevue | Washington | 98004 | United States |
| L V Prasad Eye Hospital | Hyderabad | Andhra Pradesh | India |
| Sri Sankaradeva Nethralaya | Guwahati | Assam | India |
| M&J Western Regional Institute of Ophthalmology | Ahmedabad | Gujarat | India |
| JSS Hospital | Mysore | Karnataka | India |
| Regional Institute of Ophthalmology | Thiruvananthapuram | Kerala | India |
| TN Medical College and BYL Nair Hospital | Mumbai | Maharashtra | India |
| PBMA's H V Desai Eye Hospital | Pune | Maharashtra | India |
| Sankara Nethralaya | Chennai | Tamil Nadu | India |
| Sankara Eye Hospital | Coimbatore | Tamil Nadu | India |
| King George's Medical University | Lucknow | Uttar Pradesh | India |
| Sanjay Gandhi Postgraduate Institute of Medical Sciences | Lucknow | Uttar Pradesh | India |
| Icare Eye Hospital & PG Institute | Noida | Uttar Pradesh | India |
| Calcutta Medical Research Institute | Kolkata | 700027 | India |
| Disha Eye Hospital | Kolkata | India |
| Dr Rajendra Prasad Centre for Ophthalmic Sciences | New Delhi | 110029 | India |
| Dr. Shroff's Charity Eye Hospital | New Delhi | India |
| Soroka Medical Center | Beersheba | 85025 | Israel |
| Bnai Zion Medical Center | Haifa | 3104802 | Israel |
| Rambam Health Corp | Haifa | 3109601 | Israel |
| Hadassah-Hebrew University Medical Center | Jerusalem | 91120 | Israel |
| Rabin Medical Center | Petah Tikva | 4941492 | Israel |
| Sheba Medical Center | Ramat Gan | 52621 | Israel |
| Kaplan Medical Center | Rehovot | 76100 | Israel |
| Tel-Aviv Sourasky Medical Center | Tel Aviv | 64239 | Israel |
| 36055922 | Derived | Bhattacharyya S, Hariprasad SM, Albini TA, Dutta SK, John D, Padula WV, Harrison D, Joseph G. Suprachoroidal Injection of Triamcinolone Acetonide Injectable Suspension for the Treatment of Macular Edema Associated With Uveitis in the United States: A Cost-Effectiveness Analysis. Value Health. 2022 Oct;25(10):1705-1716. doi: 10.1016/j.jval.2022.07.008. Epub 2022 Aug 31. |
| 34741564 | Derived | Singer MA, Merrill P, Yeh S, Hall C, Kapik B, Ciulla TA. Suprachoroidal triamcinolone acetonide versus rescue therapies for the treatment of uveitic macular oedema: A post hoc analysis of PEACHTREE. Clin Exp Ophthalmol. 2022 Jan;50(1):23-30. doi: 10.1111/ceo.14024. Epub 2021 Dec 27. |
| 34322164 | Derived | Price KW, Albini TA, Yeh S. Suprachoroidal Injection of Triamcinolone- Review of a Novel Treatment for Macular Edema Caused by Noninfectious Uveitis. US Ophthalmic Rev. 2020 Fall;13(2):76-79. doi: 10.17925/usor.2020.13.2.76. Epub 2020 Dec 23. |
Matching suprachoroidal syringe with sham procedure Sham Procedure: Sham procedure administered at 2 timepoints |
| Intention-to-Treat (ITT) Population | Defined as all randomized subjects who received at least one study treatment. Subjects analyzed as originally allocated after randomization. |
|
| Safety Population | Defined as all randomized subjects who were administered at least one dose of study drug. |
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| COMPLETED |
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| NOT COMPLETED |
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The Intent-to-treat population included all randomized subjects who received at least one study treatment.
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| ID | Title | Description |
|---|---|---|
| BG000 | 4mg CLS-TA Suprachoriodal Injection | Suprachoroidal injection of 40 mg/mL (4 mg in 100 µL) of CLS-TA 4mg CLS-TA Suprachoriodal Injection: CLS-TA, 40 mg/mL (4 mg in 100 µL), administered as a single injection at 2 timepoints |
| BG001 | Sham Procedure | Matching suprachoroidal syringe with sham procedure Sham Procedure: Sham procedure administered at 2 timepoints |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Age of subjects in years relative to the date of the Screening visit. | Count of Participants | Participants |
| |||||||||||||||||
| Age, Continuous | Age of subjects in years relative to the date of the Screening visit. | Mean | Standard Deviation | years |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||||
| Type of Uveitis | Location of inflammation in the study eye, including anterior (anterior chamber), intermediate (vitreous), posterior (retina or choroid) and panuveitis. | Count of Participants | 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 Subjects Demonstrating ≥ 15 Letter Improvement From Baseline in Best Corrected Visual Acuity at 24 Weeks | 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 electronic Visual Acuity (eVA). 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 one study treatment. | Posted | Count of Participants | Participants | Baseline, 24 weeks |
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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. Only images that were gradable by the central reading center were included in the analysis. | The Intent-to-treat population included all randomized subjects who received at least one study treatment. Analysis included all subjects with gradable reading center images. | Posted | Mean | Standard Deviation | microns | Baseline, 24 weeks |
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| Secondary | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Number of subjects with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) reported between the first dose of study drug and study exit. | The Safety population included all randomized subjects who were administered at least one dose of the study drug. | Posted | Count of Participants | Participants | Baseline to 24 weeks |
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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 | 4mg CLS-TA Suprachoriodal Injection | Suprachoroidal injection of 40 mg/mL (4 mg in 100 µL) of CLS-TA 4mg CLS-TA Suprachoriodal Injection: CLS-TA, 40 mg/mL (4 mg in 100 µL), administered as a single injection at 2 timepoints | 0 | 96 | 3 | 96 | 42 | 96 |
| EG001 | Sham Procedure | Matching suprachoroidal syringe with sham procedure Sham Procedure: Sham procedure administered at 2 timepoints | 0 | 64 | 0 | 64 | 29 | 64 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sialoadenitis | Infections and infestations | MedDRA (18.1) | Non-systematic Assessment |
| |
| Lumbar vertebral fracture | Injury, poisoning and procedural complications | MedDRA (18.1) | Non-systematic Assessment |
| |
| Retinal detachment | Eye disorders | MedDRA (18.1) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA (18.1) | Non-systematic Assessment |
| |
| Cataract subcapsular | Eye disorders | MedDRA (18.1) | Non-systematic Assessment | #Study eye |
|
| Cystoid macular oedema | Eye disorders | MedDRA (18.1) | Non-systematic Assessment | #Study eye |
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| Eye pain | Eye disorders | MedDRA (18.1) | Non-systematic Assessment | #Study eye |
|
| Ocular hypertension | Eye disorders | MedDRA (18.1) | Non-systematic Assessment | #Study eye |
|
| Uveitis | Eye disorders | MedDRA (18.1) | Non-systematic Assessment | #Study eye |
|
| Intraocular pressure increased | Investigations | MedDRA (18.1) | Non-systematic Assessment | #Study eye |
|
| Intraocular pressure increased | Investigations | MedDRA (18.1) | Non-systematic Assessment | #Fellow eye |
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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 the Sponsor.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Thomas Ciulla, MD MBA | Clearside Biomedical, Inc. | (678) 392-2318 | thomas.ciulla@clearsidebio.com |
| Mar 8, 2021 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D014605 | Uveitis |
| D015866 | Uveitis, Posterior |
| D014606 | Uveitis, Anterior |
| D015867 | Uveitis, Intermediate |
| D015864 | Panuveitis |
| ID | Term |
|---|---|
| D014603 | Uveal Diseases |
| D005128 | Eye Diseases |
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| ID | Term |
|---|---|
| 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 |
|
| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
|
| 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 |
|
| Unknown or Not Reported |
|
| Israel |
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| India |
|
| Intermediate uveitis |
|
| Posterior uveitis |
|
| Panuveitis |
|
Estimated value was calculated as the percentage of subjects in the Active arm meeting the primary endpoint minus the percentage of subjects in the Control arm meeting the primary endpoint. |
| Superiority |
| Participants |
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