Panuveitis, Uveitis, Uveitis, Anterior, Uveitis, Intermediate, Uveitis, Posterior
Conditions
Keywords
Uveitis, UME, Posterior Uveitis, Anterior Uveitis, Intermediate Uveitis, Panuveitis, Non-infectious Uveitis, Triamcinolone, Choroid, Choroidal Injection, Suprachoroidal, Microneedle, Microinjection, Triamcinolone acetonide
Brief summary
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.
Detailed description
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).
Interventions
DRUG4mg CLS-TA Suprachoriodal Injection
CLS-TA, 40 mg/mL (4 mg in 100 µL), administered as a single injection at 2 timepoints
DRUGSham Procedure
Sham procedure administered at 2 timepoints
Sponsors
Clearside Biomedical, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of non-infectious uveitis (pan, anterior, intermediate and posterior) * Diagnosis of macular edema associated with non-infectious uveitis (retinal thickness ≥ 300 microns) * Visual Acuity score of ≥ 5 letters read (20/800 Snellen equivalent) and ≤ 70 letters read (20/40 Snellen equivalent), in the study eye
Exclusion criteria
* Any active ocular disease or infection in the study eye other than uveitis * Intraocular pressure \> 22 mmHg or uncontrolled glaucoma in the study eye; subjects are not excluded if IOP ≤ 22 mmHg with no more than 2 IOP lowering medications. * Any uncontrolled systemic disease that, in the opinion of the Investigator, would preclude participation in the study * Any topical ocular corticosteroid in the 10 days prior to baseline; intraocular or periocular corticosteroid injections in the 2 months prior to baseline; an OZURDEX implant in the 6 months prior to baseline; RETISERT or ILUVIEN implant in the 3 years prior to baseline.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Demonstrating ≥ 15 Letter Improvement From Baseline in Best Corrected Visual Acuity at 24 Weeks | Baseline, 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Central Subfield Thickness | Baseline, 24 weeks | 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. |
| Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Baseline to 24 weeks | 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. |
Countries
India, Israel, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 96 |
| Sham Procedure Matching suprachoroidal syringe with sham procedure
Sham Procedure: Sham procedure administered at 2 timepoints | 64 |
| Total | 160 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Non-compliance | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Sham Procedure | 4mg CLS-TA Suprachoriodal Injection | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 12 Participants | 16 Participants | 28 Participants |
| Age, Categorical Between 18 and 65 years | 52 Participants | 79 Participants | 131 Participants |
| Age, Continuous | 50.00 years STANDARD_DEVIATION 15.083 | 50.40 years STANDARD_DEVIATION 14.18 | 50.24 years STANDARD_DEVIATION 14.502 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 10 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 58 Participants | 86 Participants | 144 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 28 Participants | 44 Participants | 72 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 11 Participants | 22 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 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 | 25 Participants | 40 Participants | 65 Participants |
| Region of Enrollment India | 27 participants | 43 participants | 70 participants |
| Region of Enrollment Israel | 3 participants | 7 participants | 10 participants |
| Region of Enrollment United States | 34 participants | 46 participants | 80 participants |
| Sex: Female, Male Female | 34 Participants | 54 Participants | 88 Participants |
| Sex: Female, Male Male | 30 Participants | 42 Participants | 72 Participants |
| Type of Uveitis Anterior uveitis | 14 Participants | 27 Participants | 41 Participants |
| Type of Uveitis Intermediate uveitis | 23 Participants | 34 Participants | 57 Participants |
| Type of Uveitis Panuveitis | 24 Participants | 28 Participants | 52 Participants |
| Type of Uveitis Posterior uveitis | 13 Participants | 22 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 96 | 0 / 64 |
| other Total, other adverse events | 42 / 96 | 29 / 64 |
| serious Total, serious adverse events | 3 / 96 | 0 / 64 |
Outcome results
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.
Time frame: Baseline, 24 weeks
Population: The Intent-to-treat population included all randomized subjects who received at least one study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 4mg CLS-TA Suprachoriodal Injection | Number of Subjects Demonstrating ≥ 15 Letter Improvement From Baseline in Best Corrected Visual Acuity at 24 Weeks | 45 Participants |
| Sham Procedure | Number of Subjects Demonstrating ≥ 15 Letter Improvement From Baseline in Best Corrected Visual Acuity at 24 Weeks | 10 Participants |
Comparison: A total sample size of 150 subjects in a 3:2 randomization had 90% power to detect a difference between treatments in the proportion of subjects showing improvement is 0.60 for treated and 0.34 for sham. The primary analysis was a test of superiority of the CLS-TA arm over the sham arm, and was based on a Cochran-Mantel-Haenszel chi-square test stratified by country.p-value: <0.00195% CI: [15.5, 45.9]Cochran-Mantel-Haenszel
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.
Time frame: Baseline, 24 weeks
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 4mg CLS-TA Suprachoriodal Injection | Mean Change From Baseline in Central Subfield Thickness | -152.6 microns | Standard Deviation 159.14 |
| Sham Procedure | Mean Change From Baseline in Central Subfield Thickness | -17.9 microns | Standard Deviation 150.98 |
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.
Time frame: Baseline to 24 weeks
Population: The Safety population included all randomized subjects who were administered at least one dose of the study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 4mg CLS-TA Suprachoriodal Injection | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Experiencing at least one TEAE | 67 Participants |
| 4mg CLS-TA Suprachoriodal Injection | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Experiencing at least one SAE | 3 Participants |
| Sham Procedure | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Experiencing at least one TEAE | 45 Participants |
| Sham Procedure | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Experiencing at least one SAE | 0 Participants |