Macular Edema, Retinal Vein Occlusion
Conditions
Keywords
RVO, ME, Central Subfield Thickness, OCT, Optical Coherence Tomography, Cystoid Macular Edema, Subretinal Fluid, Eylea, Aflibercept, Anti-VEGF, Suprachoroidal, Triamcinolone acetonide
Brief summary
This is a Phase 3, multicenter, randomized, masked, controlled, parallel group study of 12 months duration in treatment naïve subjects with RVO.
Detailed description
A randomized, masked, controlled trial to study the safety and efficacy of suprachoroidal CLS-TA in conjunction with intravitreal aflibercept in subjects with retinal vein occlusion
Interventions
suprachoroidal injection of CLS-TA
suprachoroidal sham procedure
DRUGIVT aflibercept
2 mg intravitreal injection of aflibercept
Sponsors
Clearside Biomedical, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has a clinical diagnosis of RVO in the study eye * Has a CST of ≥ 300 µm in the study eye * Has an ETDRS BCVA score of ≥ 20 letters read and ≤ 70 letters read in the study eye; * Is naïve to local pharmacologic treatment for RVO in the study eye;
Exclusion criteria
* Any active ocular disease or infection in the study eye other than RVO * History of glaucoma, intraocular pressure \> 21 mmHg or ocular hypertension requiring more than one medication * Any uncontrolled systemic disease that, in the opinion of the Investigator, would preclude participation in the study * Any evidence of neovascularization in the study eye
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Demonstrating ≥ 15 Letter Improvement From Baseline in Early Treatment of Diabetic Retinopathy Study (ETDRS) | 2 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Best Corrected Visual Acuity | 6 months | 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. A positive change from baseline value represents an improvement in vision. |
| Mean Change From Baseline in Central Subfield Thickness | 6 months | 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. |
Countries
Australia, Austria, Canada, Denmark, Hungary, India, Israel, Italy, Philippines, Poland, Portugal, Slovakia, Spain, Taiwan, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active IVT aflibercept (2 mg/0.05 mL) + CLS-TA (4 mg/100 µL) SC injections
suprachoroidal CLS-TA: suprachoroidal injection of CLS-TA
IVT aflibercept: 2 mg intravitreal injection of aflibercept | 231 |
| Control IVT aflibercept (2 mg/0.05 mL) + sham SC procedure
suprachoroidal sham: suprachoroidal sham procedure
IVT aflibercept: 2 mg intravitreal injection of aflibercept | 229 |
| Total | 460 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 7 |
| Overall Study | Includes premature discontinuation due to study termination. | 88 | 88 |
| Overall Study | Lost to Follow-up | 5 | 5 |
| Overall Study | Unknown study completion status | 1 | 0 |
| Overall Study | Withdrawal by Subject | 7 | 2 |
Baseline characteristics
| Characteristic | Control | Total | Active |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 122 Participants | 264 Participants | 142 Participants |
| Age, Categorical Between 18 and 65 years | 107 Participants | 196 Participants | 89 Participants |
| Age, Continuous | 64.9 Years STANDARD_DEVIATION 12.42 | 65.7 Years STANDARD_DEVIATION 12.37 | 66.4 Years STANDARD_DEVIATION 12.31 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 40 Participants | 73 Participants | 33 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 22 Participants | 10 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 | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) White | 177 Participants | 358 Participants | 181 Participants |
| Region of Enrollment Australia | 6 Participants | 15 Participants | 9 Participants |
| Region of Enrollment Canada | 3 Participants | 5 Participants | 2 Participants |
| Region of Enrollment Denmark | 1 Participants | 3 Participants | 2 Participants |
| Region of Enrollment Hungary | 1 Participants | 7 Participants | 6 Participants |
| Region of Enrollment India | 19 Participants | 32 Participants | 13 Participants |
| Region of Enrollment Philippines | 3 Participants | 3 Participants | 0 Participants |
| Region of Enrollment Poland | 5 Participants | 10 Participants | 5 Participants |
| Region of Enrollment Portugal | 2 Participants | 5 Participants | 3 Participants |
| Region of Enrollment Slovakia | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment Spain | 2 Participants | 5 Participants | 3 Participants |
| Region of Enrollment Taiwan | 1 Participants | 3 Participants | 2 Participants |
| Region of Enrollment United Kingdom | 2 Participants | 6 Participants | 4 Participants |
| Region of Enrollment United States | 183 Participants | 365 Participants | 182 Participants |
| Sex: Female, Male Female | 105 Participants | 202 Participants | 97 Participants |
| Sex: Female, Male Male | 124 Participants | 258 Participants | 134 Participants |
| Type of Retinal Vein Occlusion Branch retinal vein occlusion | 124 Participants | 248 Participants | 124 Participants |
| Type of Retinal Vein Occlusion Central retinal vein occlusion | 105 Participants | 212 Participants | 107 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 231 | 0 / 229 |
| other Total, other adverse events | 128 / 231 | 83 / 229 |
| serious Total, serious adverse events | 25 / 231 | 28 / 229 |
Outcome results
Primary
Proportion of Subjects Demonstrating ≥ 15 Letter Improvement From Baseline in Early Treatment of Diabetic Retinopathy Study (ETDRS)
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.
Time frame: 2 months
Population: The Intent-to-treat population included all randomized subjects who received at least one study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active | Proportion of Subjects Demonstrating ≥ 15 Letter Improvement From Baseline in Early Treatment of Diabetic Retinopathy Study (ETDRS) | 114 Participants |
| Control | Proportion of Subjects Demonstrating ≥ 15 Letter Improvement From Baseline in Early Treatment of Diabetic Retinopathy Study (ETDRS) | 127 Participants |
Comparison: Based on a Pearson chi-square test, a total sample size of approximately 460 subjects provided 90% power to detect a difference of 15% between the Active and Control arms assuming the Control arm showed a proportion of 0.50 at 8 weeks. The primary analysis was a test of superiority of the Active arm over the Control arm, and was based on a Cochran-Mantel-Haenszel chi-square test stratified by type of retinal vein occlusion.p-value: 0.18795% CI: [-15.2, 3]Cochran-Mantel-Haenszel
Secondary
Mean Change From Baseline in 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 in the number of letters read correctly on an ETDRS eye chart. A positive change from baseline value represents an improvement in vision.
Time frame: 6 months
Population: The Intent-to-treat population included all randomized subjects who received at least one study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Active | Mean Change From Baseline in Best Corrected Visual Acuity | 15.5 Letters | Standard Error 0.85 |
| Control | Mean Change From Baseline in Best Corrected Visual Acuity | 20.5 Letters | Standard Error 0.85 |
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.
Time frame: 6 months
Population: The Intent-to-treat population included all randomized subjects who received at least one study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Active | Mean Change From Baseline in Central Subfield Thickness | -354.3 Microns | Standard Error 8.01 |
| Control | Mean Change From Baseline in Central Subfield Thickness | -416.2 Microns | Standard Error 8.05 |